TY - JOUR T1 - Genomic analyses identify hundreds of variants associated with age at menarche and support a role for puberty timing in cancer risk. JF - Nat Genet Y1 - 2017 A1 - Day, Felix R A1 - Thompson, Deborah J A1 - Helgason, Hannes A1 - Chasman, Daniel I A1 - Finucane, Hilary A1 - Sulem, Patrick A1 - Ruth, Katherine S A1 - Whalen, Sean A1 - Sarkar, Abhishek K A1 - Albrecht, Eva A1 - Altmaier, Elisabeth A1 - Amini, Marzyeh A1 - Barbieri, Caterina M A1 - Boutin, Thibaud A1 - Campbell, Archie A1 - Demerath, Ellen A1 - Giri, Ayush A1 - He, Chunyan A1 - Hottenga, Jouke J A1 - Karlsson, Robert A1 - Kolcic, Ivana A1 - Loh, Po-Ru A1 - Lunetta, Kathryn L A1 - Mangino, Massimo A1 - Marco, Brumat A1 - McMahon, George A1 - Medland, Sarah E A1 - Nolte, Ilja M A1 - Noordam, Raymond A1 - Nutile, Teresa A1 - Paternoster, Lavinia A1 - Perjakova, Natalia A1 - Porcu, Eleonora A1 - Rose, Lynda M A1 - Schraut, Katharina E A1 - Segrè, Ayellet V A1 - Smith, Albert V A1 - Stolk, Lisette A1 - Teumer, Alexander A1 - Andrulis, Irene L A1 - Bandinelli, Stefania A1 - Beckmann, Matthias W A1 - Benitez, Javier A1 - Bergmann, Sven A1 - Bochud, Murielle A1 - Boerwinkle, Eric A1 - Bojesen, Stig E A1 - Bolla, Manjeet K A1 - Brand, Judith S A1 - Brauch, Hiltrud A1 - Brenner, Hermann A1 - Broer, Linda A1 - Brüning, Thomas A1 - Buring, Julie E A1 - Campbell, Harry A1 - Catamo, Eulalia A1 - Chanock, Stephen A1 - Chenevix-Trench, Georgia A1 - Corre, Tanguy A1 - Couch, Fergus J A1 - Cousminer, Diana L A1 - Cox, Angela A1 - Crisponi, Laura A1 - Czene, Kamila A1 - Davey Smith, George A1 - de Geus, Eco J C N A1 - de Mutsert, Renée A1 - De Vivo, Immaculata A1 - Dennis, Joe A1 - Devilee, Peter A1 - Dos-Santos-Silva, Isabel A1 - Dunning, Alison M A1 - Eriksson, Johan G A1 - Fasching, Peter A A1 - Fernández-Rhodes, Lindsay A1 - Ferrucci, Luigi A1 - Flesch-Janys, Dieter A1 - Franke, Lude A1 - Gabrielson, Marike A1 - Gandin, Ilaria A1 - Giles, Graham G A1 - Grallert, Harald A1 - Gudbjartsson, Daniel F A1 - Guenel, Pascal A1 - Hall, Per A1 - Hallberg, Emily A1 - Hamann, Ute A1 - Harris, Tamara B A1 - Hartman, Catharina A A1 - Heiss, Gerardo A1 - Hooning, Maartje J A1 - Hopper, John L A1 - Hu, Frank A1 - Hunter, David J A1 - Ikram, M Arfan A1 - Im, Hae Kyung A1 - Järvelin, Marjo-Riitta A1 - Joshi, Peter K A1 - Karasik, David A1 - Kellis, Manolis A1 - Kutalik, Zoltán A1 - LaChance, Genevieve A1 - Lambrechts, Diether A1 - Langenberg, Claudia A1 - Launer, Lenore J A1 - Laven, Joop S E A1 - Lenarduzzi, Stefania A1 - Li, Jingmei A1 - Lind, Penelope A A1 - Lindström, Sara A1 - Liu, Yongmei A1 - Luan, Jian'an A1 - Mägi, Reedik A1 - Mannermaa, Arto A1 - Mbarek, Hamdi A1 - McCarthy, Mark I A1 - Meisinger, Christa A1 - Meitinger, Thomas A1 - Menni, Cristina A1 - Metspalu, Andres A1 - Michailidou, Kyriaki A1 - Milani, Lili A1 - Milne, Roger L A1 - Montgomery, Grant W A1 - Mulligan, Anna M A1 - Nalls, Mike A A1 - Navarro, Pau A1 - Nevanlinna, Heli A1 - Nyholt, Dale R A1 - Oldehinkel, Albertine J A1 - O'Mara, Tracy A A1 - Padmanabhan, Sandosh A1 - Palotie, Aarno A1 - Pedersen, Nancy A1 - Peters, Annette A1 - Peto, Julian A1 - Pharoah, Paul D P A1 - Pouta, Anneli A1 - Radice, Paolo A1 - Rahman, Iffat A1 - Ring, Susan M A1 - Robino, Antonietta A1 - Rosendaal, Frits R A1 - Rudan, Igor A1 - Rueedi, Rico A1 - Ruggiero, Daniela A1 - Sala, Cinzia F A1 - Schmidt, Marjanka K A1 - Scott, Robert A A1 - Shah, Mitul A1 - Sorice, Rossella A1 - Southey, Melissa C A1 - Sovio, Ulla A1 - Stampfer, Meir A1 - Steri, Maristella A1 - Strauch, Konstantin A1 - Tanaka, Toshiko A1 - Tikkanen, Emmi A1 - Timpson, Nicholas J A1 - Traglia, Michela A1 - Truong, Therese A1 - Tyrer, Jonathan P A1 - Uitterlinden, André G A1 - Edwards, Digna R Velez A1 - Vitart, Veronique A1 - Völker, Uwe A1 - Vollenweider, Peter A1 - Wang, Qin A1 - Widen, Elisabeth A1 - van Dijk, Ko Willems A1 - Willemsen, Gonneke A1 - Winqvist, Robert A1 - Wolffenbuttel, Bruce H R A1 - Zhao, Jing Hua A1 - Zoledziewska, Magdalena A1 - Zygmunt, Marek A1 - Alizadeh, Behrooz Z A1 - Boomsma, Dorret I A1 - Ciullo, Marina A1 - Cucca, Francesco A1 - Esko, Tõnu A1 - Franceschini, Nora A1 - Gieger, Christian A1 - Gudnason, Vilmundur A1 - Hayward, Caroline A1 - Kraft, Peter A1 - Lawlor, Debbie A A1 - Magnusson, Patrik K E A1 - Martin, Nicholas G A1 - Mook-Kanamori, Dennis O A1 - Nohr, Ellen A A1 - Polasek, Ozren A1 - Porteous, David A1 - Price, Alkes L A1 - Ridker, Paul M A1 - Snieder, Harold A1 - Spector, Tim D A1 - Stöckl, Doris A1 - Toniolo, Daniela A1 - Ulivi, Sheila A1 - Visser, Jenny A A1 - Völzke, Henry A1 - Wareham, Nicholas J A1 - Wilson, James F A1 - Spurdle, Amanda B A1 - Thorsteindottir, Unnur A1 - Pollard, Katherine S A1 - Easton, Douglas F A1 - Tung, Joyce Y A1 - Chang-Claude, Jenny A1 - Hinds, David A1 - Murray, Anna A1 - Murabito, Joanne M A1 - Stefansson, Kari A1 - Ong, Ken K A1 - Perry, John R B KW - Adolescent KW - Age Factors KW - Body Mass Index KW - Databases, Genetic KW - Female KW - Genetic Predisposition to Disease KW - Genome-Wide Association Study KW - Genomic Imprinting KW - Humans KW - Intercellular Signaling Peptides and Proteins KW - Male KW - Membrane Proteins KW - Menarche KW - Neoplasms KW - Polymorphism, Single Nucleotide KW - Puberty KW - Quantitative Trait Loci KW - Ribonucleoproteins KW - Risk Factors AB -

The timing of puberty is a highly polygenic childhood trait that is epidemiologically associated with various adult diseases. Using 1000 Genomes Project-imputed genotype data in up to ∼370,000 women, we identify 389 independent signals (P < 5 × 10) for age at menarche, a milestone in female pubertal development. In Icelandic data, these signals explain ∼7.4% of the population variance in age at menarche, corresponding to ∼25% of the estimated heritability. We implicate ∼250 genes via coding variation or associated expression, demonstrating significant enrichment in neural tissues. Rare variants near the imprinted genes MKRN3 and DLK1 were identified, exhibiting large effects when paternally inherited. Mendelian randomization analyses suggest causal inverse associations, independent of body mass index (BMI), between puberty timing and risks for breast and endometrial cancers in women and prostate cancer in men. In aggregate, our findings highlight the complexity of the genetic regulation of puberty timing and support causal links with cancer susceptibility.

VL - 49 IS - 6 U1 - http://www.ncbi.nlm.nih.gov/pubmed/28436984?dopt=Abstract ER - TY - JOUR T1 - Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function. JF - Nat Commun Y1 - 2016 A1 - Pattaro, Cristian A1 - Teumer, Alexander A1 - Gorski, Mathias A1 - Chu, Audrey Y A1 - Li, Man A1 - Mijatovic, Vladan A1 - Garnaas, Maija A1 - Tin, Adrienne A1 - Sorice, Rossella A1 - Li, Yong A1 - Taliun, Daniel A1 - Olden, Matthias A1 - Foster, Meredith A1 - Yang, Qiong A1 - Chen, Ming-Huei A1 - Pers, Tune H A1 - Johnson, Andrew D A1 - Ko, Yi-An A1 - Fuchsberger, Christian A1 - Tayo, Bamidele A1 - Nalls, Michael A1 - Feitosa, Mary F A1 - Isaacs, Aaron A1 - Dehghan, Abbas A1 - d'Adamo, Pio A1 - Adeyemo, Adebowale A1 - Dieffenbach, Aida Karina A1 - Zonderman, Alan B A1 - Nolte, Ilja M A1 - van der Most, Peter J A1 - Wright, Alan F A1 - Shuldiner, Alan R A1 - Morrison, Alanna C A1 - Hofman, Albert A1 - Smith, Albert V A1 - Dreisbach, Albert W A1 - Franke, Andre A1 - Uitterlinden, André G A1 - Metspalu, Andres A1 - Tönjes, Anke A1 - Lupo, Antonio A1 - Robino, Antonietta A1 - Johansson, Åsa A1 - Demirkan, Ayse A1 - Kollerits, Barbara A1 - Freedman, Barry I A1 - Ponte, Belen A1 - Oostra, Ben A A1 - Paulweber, Bernhard A1 - Krämer, Bernhard K A1 - Mitchell, Braxton D A1 - Buckley, Brendan M A1 - Peralta, Carmen A A1 - Hayward, Caroline A1 - Helmer, Catherine A1 - Rotimi, Charles N A1 - Shaffer, Christian M A1 - Müller, Christian A1 - Sala, Cinzia A1 - van Duijn, Cornelia M A1 - Saint-Pierre, Aude A1 - Ackermann, Daniel A1 - Shriner, Daniel A1 - Ruggiero, Daniela A1 - Toniolo, Daniela A1 - Lu, Yingchang A1 - Cusi, Daniele A1 - Czamara, Darina A1 - Ellinghaus, David A1 - Siscovick, David S A1 - Ruderfer, Douglas A1 - Gieger, Christian A1 - Grallert, Harald A1 - Rochtchina, Elena A1 - Atkinson, Elizabeth J A1 - Holliday, Elizabeth G A1 - Boerwinkle, Eric A1 - Salvi, Erika A1 - Bottinger, Erwin P A1 - Murgia, Federico A1 - Rivadeneira, Fernando A1 - Ernst, Florian A1 - Kronenberg, Florian A1 - Hu, Frank B A1 - Navis, Gerjan J A1 - Curhan, Gary C A1 - Ehret, George B A1 - Homuth, Georg A1 - Coassin, Stefan A1 - Thun, Gian-Andri A1 - Pistis, Giorgio A1 - Gambaro, Giovanni A1 - Malerba, Giovanni A1 - Montgomery, Grant W A1 - Eiriksdottir, Gudny A1 - Jacobs, Gunnar A1 - Li, Guo A1 - Wichmann, H-Erich A1 - Campbell, Harry A1 - Schmidt, Helena A1 - Wallaschofski, Henri A1 - Völzke, Henry A1 - Brenner, Hermann A1 - Kroemer, Heyo K A1 - Kramer, Holly A1 - Lin, Honghuang A1 - Leach, I Mateo A1 - Ford, Ian A1 - Guessous, Idris A1 - Rudan, Igor A1 - Prokopenko, Inga A1 - Borecki, Ingrid A1 - Heid, Iris M A1 - Kolcic, Ivana A1 - Persico, Ivana A1 - Jukema, J Wouter A1 - Wilson, James F A1 - Felix, Janine F A1 - Divers, Jasmin A1 - Lambert, Jean-Charles A1 - Stafford, Jeanette M A1 - Gaspoz, Jean-Michel A1 - Smith, Jennifer A A1 - Faul, Jessica D A1 - Wang, Jie Jin A1 - Ding, Jingzhong A1 - Hirschhorn, Joel N A1 - Attia, John A1 - Whitfield, John B A1 - Chalmers, John A1 - Viikari, Jorma A1 - Coresh, Josef A1 - Denny, Joshua C A1 - Karjalainen, Juha A1 - Fernandes, Jyotika K A1 - Endlich, Karlhans A1 - Butterbach, Katja A1 - Keene, Keith L A1 - Lohman, Kurt A1 - Portas, Laura A1 - Launer, Lenore J A1 - Lyytikäinen, Leo-Pekka A1 - Yengo, Loic A1 - Franke, Lude A1 - Ferrucci, Luigi A1 - Rose, Lynda M A1 - Kedenko, Lyudmyla A1 - Rao, Madhumathi A1 - Struchalin, Maksim A1 - Kleber, Marcus E A1 - Cavalieri, Margherita A1 - Haun, Margot A1 - Cornelis, Marilyn C A1 - Ciullo, Marina A1 - Pirastu, Mario A1 - de Andrade, Mariza A1 - McEvoy, Mark A A1 - Woodward, Mark A1 - Adam, Martin A1 - Cocca, Massimiliano A1 - Nauck, Matthias A1 - Imboden, Medea A1 - Waldenberger, Melanie A1 - Pruijm, Menno A1 - Metzger, Marie A1 - Stumvoll, Michael A1 - Evans, Michele K A1 - Sale, Michele M A1 - Kähönen, Mika A1 - Boban, Mladen A1 - Bochud, Murielle A1 - Rheinberger, Myriam A1 - Verweij, Niek A1 - Bouatia-Naji, Nabila A1 - Martin, Nicholas G A1 - Hastie, Nick A1 - Probst-Hensch, Nicole A1 - Soranzo, Nicole A1 - Devuyst, Olivier A1 - Raitakari, Olli A1 - Gottesman, Omri A1 - Franco, Oscar H A1 - Polasek, Ozren A1 - Gasparini, Paolo A1 - Munroe, Patricia B A1 - Ridker, Paul M A1 - Mitchell, Paul A1 - Muntner, Paul A1 - Meisinger, Christa A1 - Smit, Johannes H A1 - Kovacs, Peter A1 - Wild, Philipp S A1 - Froguel, Philippe A1 - Rettig, Rainer A1 - Mägi, Reedik A1 - Biffar, Reiner A1 - Schmidt, Reinhold A1 - Middelberg, Rita P S A1 - Carroll, Robert J A1 - Penninx, Brenda W A1 - Scott, Rodney J A1 - Katz, Ronit A1 - Sedaghat, Sanaz A1 - Wild, Sarah H A1 - Kardia, Sharon L R A1 - Ulivi, Sheila A1 - Hwang, Shih-Jen A1 - Enroth, Stefan A1 - Kloiber, Stefan A1 - Trompet, Stella A1 - Stengel, Bénédicte A1 - Hancock, Stephen J A1 - Turner, Stephen T A1 - Rosas, Sylvia E A1 - Stracke, Sylvia A1 - Harris, Tamara B A1 - Zeller, Tanja A1 - Zemunik, Tatijana A1 - Lehtimäki, Terho A1 - Illig, Thomas A1 - Aspelund, Thor A1 - Nikopensius, Tiit A1 - Esko, Tõnu A1 - Tanaka, Toshiko A1 - Gyllensten, Ulf A1 - Völker, Uwe A1 - Emilsson, Valur A1 - Vitart, Veronique A1 - Aalto, Ville A1 - Gudnason, Vilmundur A1 - Chouraki, Vincent A1 - Chen, Wei-Min A1 - Igl, Wilmar A1 - März, Winfried A1 - Koenig, Wolfgang A1 - Lieb, Wolfgang A1 - Loos, Ruth J F A1 - Liu, Yongmei A1 - Snieder, Harold A1 - Pramstaller, Peter P A1 - Parsa, Afshin A1 - O'Connell, Jeffrey R A1 - Susztak, Katalin A1 - Hamet, Pavel A1 - Tremblay, Johanne A1 - de Boer, Ian H A1 - Böger, Carsten A A1 - Goessling, Wolfram A1 - Chasman, Daniel I A1 - Köttgen, Anna A1 - Kao, W H Linda A1 - Fox, Caroline S KW - Gene Expression Regulation KW - Genetic Predisposition to Disease KW - Genome-Wide Association Study KW - Genotype KW - Humans KW - Renal Insufficiency, Chronic AB -

Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.

VL - 7 U1 - http://www.ncbi.nlm.nih.gov/pubmed/26831199?dopt=Abstract ER - TY - JOUR T1 - Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. JF - Lancet Y1 - 2015 A1 - Forouzanfar, Mohammad H A1 - Alexander, Lily A1 - Anderson, H Ross A1 - Bachman, Victoria F A1 - Biryukov, Stan A1 - Brauer, Michael A1 - Burnett, Richard A1 - Casey, Daniel A1 - Coates, Matthew M A1 - Cohen, Aaron A1 - Delwiche, Kristen A1 - Estep, Kara A1 - Frostad, Joseph J A1 - Astha, K C A1 - Kyu, Hmwe H A1 - Moradi-Lakeh, Maziar A1 - Ng, Marie A1 - Slepak, Erica Leigh A1 - Thomas, Bernadette A A1 - Wagner, Joseph A1 - Aasvang, Gunn Marit A1 - Abbafati, Cristiana A1 - Abbasoglu Ozgoren, Ayse A1 - Abd-Allah, Foad A1 - Abera, Semaw F A1 - Aboyans, Victor A1 - Abraham, Biju A1 - Abraham, Jerry Puthenpurakal A1 - Abubakar, Ibrahim A1 - Abu-Rmeileh, Niveen M E A1 - Aburto, Tania C A1 - Achoki, Tom A1 - Adelekan, Ademola A1 - Adofo, Koranteng A1 - Adou, Arsène K A1 - Adsuar, José C A1 - Afshin, Ashkan A1 - Agardh, Emilie E A1 - Al Khabouri, Mazin J A1 - Al Lami, Faris H A1 - Alam, Sayed Saidul A1 - Alasfoor, Deena A1 - Albittar, Mohammed I A1 - Alegretti, Miguel A A1 - Aleman, Alicia V A1 - Alemu, Zewdie A A1 - Alfonso-Cristancho, Rafael A1 - Alhabib, Samia A1 - Ali, Raghib A1 - Ali, Mohammed K A1 - Alla, François A1 - Allebeck, Peter A1 - Allen, Peter J A1 - Alsharif, Ubai A1 - Alvarez, Elena A1 - Alvis-Guzmán, Nelson A1 - Amankwaa, Adansi A A1 - Amare, Azmeraw T A1 - Ameh, Emmanuel A A1 - Ameli, Omid A1 - Amini, Heresh A1 - Ammar, Walid A1 - Anderson, Benjamin O A1 - Antonio, Carl Abelardo T A1 - Anwari, Palwasha A1 - Argeseanu Cunningham, Solveig A1 - Arnlöv, Johan A1 - Arsenijevic, Valentina S Arsic A1 - Artaman, Al A1 - Asghar, Rana J A1 - Assadi, Reza A1 - Atkins, Lydia S A1 - Atkinson, Charles A1 - Avila, Marco A A1 - Awuah, Baffour A1 - Badawi, Alaa A1 - Bahit, Maria C A1 - Bakfalouni, Talal A1 - Balakrishnan, Kalpana A1 - Balalla, Shivanthi A1 - Balu, Ravi Kumar A1 - Banerjee, Amitava A1 - Barber, Ryan M A1 - Barker-Collo, Suzanne L A1 - Barquera, Simon A1 - Barregard, Lars A1 - Barrero, Lope H A1 - Barrientos-Gutierrez, Tonatiuh A1 - Basto-Abreu, Ana C A1 - Basu, Arindam A1 - Basu, Sanjay A1 - Basulaiman, Mohammed O A1 - Batis Ruvalcaba, Carolina A1 - Beardsley, Justin A1 - Bedi, Neeraj A1 - Bekele, Tolesa A1 - Bell, Michelle L A1 - Benjet, Corina A1 - Bennett, Derrick A A1 - Benzian, Habib A1 - Bernabe, Eduardo A1 - Beyene, Tariku J A1 - Bhala, Neeraj A1 - Bhalla, Ashish A1 - Bhutta, Zulfiqar A A1 - Bikbov, Boris A1 - Bin Abdulhak, Aref A A1 - Blore, Jed D A1 - Blyth, Fiona M A1 - Bohensky, Megan A A1 - Bora Başara, Berrak A1 - Borges, Guilherme A1 - Bornstein, Natan M A1 - Bose, Dipan A1 - Boufous, Soufiane A1 - Bourne, Rupert R A1 - Brainin, Michael A1 - Brazinova, Alexandra A1 - Breitborde, Nicholas J A1 - Brenner, Hermann A1 - Briggs, Adam D M A1 - Broday, David M A1 - Brooks, Peter M A1 - Bruce, Nigel G A1 - Brugha, Traolach S A1 - Brunekreef, Bert A1 - Buchbinder, Rachelle A1 - Bui, Linh N A1 - Bukhman, Gene A1 - Bulloch, Andrew G A1 - Burch, Michael A1 - Burney, Peter G J A1 - Campos-Nonato, Ismael R A1 - Campuzano, Julio C A1 - Cantoral, Alejandra J A1 - Caravanos, Jack A1 - Cárdenas, Rosario A1 - Cardis, Elisabeth A1 - Carpenter, David O A1 - Caso, Valeria A1 - Castañeda-Orjuela, Carlos A A1 - Castro, Ruben E A1 - Catalá-López, Ferrán A1 - Cavalleri, Fiorella A1 - Cavlin, Alanur A1 - Chadha, Vineet K A1 - Chang, Jung-Chen A1 - Charlson, Fiona J A1 - Chen, Honglei A1 - Chen, Wanqing A1 - Chen, Zhengming A1 - Chiang, Peggy P A1 - Chimed-Ochir, Odgerel A1 - Chowdhury, Rajiv A1 - Christophi, Costas A A1 - Chuang, Ting-Wu A1 - Chugh, Sumeet S A1 - Cirillo, Massimo A1 - Claßen, Thomas K D A1 - Colistro, Valentina A1 - Colomar, Mercedes A1 - Colquhoun, Samantha M A1 - Contreras, Alejandra G A1 - Cooper, Cyrus A1 - Cooperrider, Kimberly A1 - Cooper, Leslie T A1 - Coresh, Josef A1 - Courville, Karen J A1 - Criqui, Michael H A1 - Cuevas-Nasu, Lucia A1 - Damsere-Derry, James A1 - Danawi, Hadi A1 - Dandona, Lalit A1 - Dandona, Rakhi A1 - Dargan, Paul I A1 - Davis, Adrian A1 - Davitoiu, Dragos V A1 - Dayama, Anand A1 - de Castro, E Filipa A1 - De la Cruz-Góngora, Vanessa A1 - De Leo, Diego A1 - de Lima, Graça A1 - Degenhardt, Louisa A1 - del Pozo-Cruz, Borja A1 - Dellavalle, Robert P A1 - Deribe, Kebede A1 - Derrett, Sarah A1 - Des Jarlais, Don C A1 - Dessalegn, Muluken A1 - deVeber, Gabrielle A A1 - Devries, Karen M A1 - Dharmaratne, Samath D A1 - Dherani, Mukesh K A1 - Dicker, Daniel A1 - Ding, Eric L A1 - Dokova, Klara A1 - Dorsey, E Ray A1 - Driscoll, Tim R A1 - Duan, Leilei A1 - Durrani, Adnan M A1 - Ebel, Beth E A1 - Ellenbogen, Richard G A1 - Elshrek, Yousef M A1 - Endres, Matthias A1 - Ermakov, Sergey P A1 - Erskine, Holly E A1 - Eshrati, Babak A1 - Esteghamati, Alireza A1 - Fahimi, Saman A1 - Faraon, Emerito Jose A A1 - Farzadfar, Farshad A1 - Fay, Derek F J A1 - Feigin, Valery L A1 - Feigl, Andrea B A1 - Fereshtehnejad, Seyed-Mohammad A1 - Ferrari, Alize J A1 - Ferri, Cleusa P A1 - Flaxman, Abraham D A1 - Fleming, Thomas D A1 - Foigt, Nataliya A1 - Foreman, Kyle J A1 - Paleo, Urbano Fra A1 - Franklin, Richard C A1 - Gabbe, Belinda A1 - Gaffikin, Lynne A1 - Gakidou, Emmanuela A1 - Gamkrelidze, Amiran A1 - Gankpé, Fortuné G A1 - Gansevoort, Ron T A1 - García-Guerra, Francisco A A1 - Gasana, Evariste A1 - Geleijnse, Johanna M A1 - Gessner, Bradford D A1 - Gething, Pete A1 - Gibney, Katherine B A1 - Gillum, Richard F A1 - Ginawi, Ibrahim A M A1 - Giroud, Maurice A1 - Giussani, Giorgia A1 - Goenka, Shifalika A1 - Goginashvili, Ketevan A1 - Gomez Dantes, Hector A1 - Gona, Philimon A1 - Gonzalez de Cosio, Teresita A1 - González-Castell, Dinorah A1 - Gotay, Carolyn C A1 - Goto, Atsushi A1 - Gouda, Hebe N A1 - Guerrant, Richard L A1 - Gugnani, Harish C A1 - Guillemin, Francis A1 - Gunnell, David A1 - Gupta, Rahul A1 - Gupta, Rajeev A1 - Gutiérrez, Reyna A A1 - Hafezi-Nejad, Nima A1 - Hagan, Holly A1 - Hagstromer, Maria A1 - Halasa, Yara A A1 - Hamadeh, Randah R A1 - Hammami, Mouhanad A1 - Hankey, Graeme J A1 - Hao, Yuantao A1 - Harb, Hilda L A1 - Haregu, Tilahun Nigatu A1 - Haro, Josep Maria A1 - Havmoeller, Rasmus A1 - Hay, Simon I A1 - Hedayati, Mohammad T A1 - Heredia-Pi, Ileana B A1 - Hernandez, Lucia A1 - Heuton, Kyle R A1 - Heydarpour, Pouria A1 - Hijar, Martha A1 - Hoek, Hans W A1 - Hoffman, Howard J A1 - Hornberger, John C A1 - Hosgood, H Dean A1 - Hoy, Damian G A1 - Hsairi, Mohamed A1 - Hu, Guoqing A1 - Hu, Howard A1 - Huang, Cheng A1 - Huang, John J A1 - Hubbell, Bryan J A1 - Huiart, Laetitia A1 - Husseini, Abdullatif A1 - Iannarone, Marissa L A1 - Iburg, Kim M A1 - Idrisov, Bulat T A1 - Ikeda, Nayu A1 - Innos, Kaire A1 - Inoue, Manami A1 - Islami, Farhad A1 - Ismayilova, Samaya A1 - Jacobsen, Kathryn H A1 - Jansen, Henrica A A1 - Jarvis, Deborah L A1 - Jassal, Simerjot K A1 - Jauregui, Alejandra A1 - Jayaraman, Sudha A1 - Jeemon, Panniyammakal A1 - Jensen, Paul N A1 - Jha, Vivekanand A1 - Jiang, Fan A1 - Jiang, Guohong A1 - Jiang, Ying A1 - Jonas, Jost B A1 - Juel, Knud A1 - Kan, Haidong A1 - Kany Roseline, Sidibe S A1 - Karam, Nadim E A1 - Karch, André A1 - Karema, Corine K A1 - Karthikeyan, Ganesan A1 - Kaul, Anil A1 - Kawakami, Norito A1 - Kazi, Dhruv S A1 - Kemp, Andrew H A1 - Kengne, Andre P A1 - Keren, Andre A1 - Khader, Yousef S A1 - Khalifa, Shams Eldin Ali Hassan A1 - Khan, Ejaz A A1 - Khang, Young-Ho A1 - Khatibzadeh, Shahab A1 - Khonelidze, Irma A1 - Kieling, Christian A1 - Kim, Daniel A1 - Kim, Sungroul A1 - Kim, Yunjin A1 - Kimokoti, Ruth W A1 - Kinfu, Yohannes A1 - Kinge, Jonas M A1 - Kissela, Brett M A1 - Kivipelto, Miia A1 - Knibbs, Luke D A1 - Knudsen, Ann Kristin A1 - Kokubo, Yoshihiro A1 - Kose, M Rifat A1 - Kosen, Soewarta A1 - Kraemer, Alexander A1 - Kravchenko, Michael A1 - Krishnaswami, Sanjay A1 - Kromhout, Hans A1 - Ku, Tiffany A1 - Kuate Defo, Barthelemy A1 - Kucuk Bicer, Burcu A1 - Kuipers, Ernst J A1 - Kulkarni, Chanda A1 - Kulkarni, Veena S A1 - Kumar, G Anil A1 - Kwan, Gene F A1 - Lai, Taavi A1 - Lakshmana Balaji, Arjun A1 - Lalloo, Ratilal A1 - Lallukka, Tea A1 - Lam, Hilton A1 - Lan, Qing A1 - Lansingh, Van C A1 - Larson, Heidi J A1 - Larsson, Anders A1 - Laryea, Dennis O A1 - Lavados, Pablo M A1 - Lawrynowicz, Alicia E A1 - Leasher, Janet L A1 - Lee, Jong-Tae A1 - Leigh, James A1 - Leung, Ricky A1 - Levi, Miriam A1 - Li, Yichong A1 - Li, Yongmei A1 - Liang, Juan A1 - Liang, Xiaofeng A1 - Lim, Stephen S A1 - Lindsay, M Patrice A1 - Lipshultz, Steven E A1 - Liu, Shiwei A1 - Liu, Yang A1 - Lloyd, Belinda K A1 - Logroscino, Giancarlo A1 - London, Stephanie J A1 - Lopez, Nancy A1 - Lortet-Tieulent, Joannie A1 - Lotufo, Paulo A A1 - Lozano, Rafael A1 - Lunevicius, Raimundas A1 - Ma, Jixiang A1 - Ma, Stefan A1 - Machado, Vasco M P A1 - MacIntyre, Michael F A1 - Magis-Rodriguez, Carlos A1 - Mahdi, Abbas A A1 - Majdan, Marek A1 - Malekzadeh, Reza A1 - Mangalam, Srikanth A1 - Mapoma, Christopher C A1 - Marape, Marape A1 - Marcenes, Wagner A1 - Margolis, David J A1 - Margono, Christopher A1 - Marks, Guy B A1 - Martin, Randall V A1 - Marzan, Melvin B A1 - Mashal, Mohammad T A1 - Masiye, Felix A1 - Mason-Jones, Amanda J A1 - Matsushita, Kunihiro A1 - Matzopoulos, Richard A1 - Mayosi, Bongani M A1 - Mazorodze, Tasara T A1 - McKay, Abigail C A1 - McKee, Martin A1 - McLain, Abigail A1 - Meaney, Peter A A1 - Medina, Catalina A1 - Mehndiratta, Man Mohan A1 - Mejia-Rodriguez, Fabiola A1 - Mekonnen, Wubegzier A1 - Melaku, Yohannes A A1 - Meltzer, Michele A1 - Memish, Ziad A A1 - Mendoza, Walter A1 - Mensah, George A A1 - Meretoja, Atte A1 - Mhimbira, Francis Apolinary A1 - Micha, Renata A1 - Miller, Ted R A1 - Mills, Edward J A1 - Misganaw, Awoke A1 - Mishra, Santosh A1 - Mohamed Ibrahim, Norlinah A1 - Mohammad, Karzan A A1 - Mokdad, Ali H A1 - Mola, Glen L A1 - Monasta, Lorenzo A1 - Montañez Hernandez, Julio C A1 - Montico, Marcella A1 - Moore, Ami R A1 - Morawska, Lidia A1 - Mori, Rintaro A1 - Moschandreas, Joanna A1 - Moturi, Wilkister N A1 - Mozaffarian, Dariush A1 - Mueller, Ulrich O A1 - Mukaigawara, Mitsuru A1 - Mullany, Erin C A1 - Murthy, Kinnari S A1 - Naghavi, Mohsen A1 - Nahas, Ziad A1 - Naheed, Aliya A1 - Naidoo, Kovin S A1 - Naldi, Luigi A1 - Nand, Devina A1 - Nangia, Vinay A1 - Narayan, K M Venkat A1 - Nash, Denis A1 - Neal, Bruce A1 - Nejjari, Chakib A1 - Neupane, Sudan P A1 - Newton, Charles R A1 - Ngalesoni, Frida N A1 - Ngirabega, Jean de Dieu A1 - Nguyen, Grant A1 - Nguyen, Nhung T A1 - Nieuwenhuijsen, Mark J A1 - Nisar, Muhammad I A1 - Nogueira, José R A1 - Nolla, Joan M A1 - Nolte, Sandra A1 - Norheim, Ole F A1 - Norman, Rosana E A1 - Norrving, Bo A1 - Nyakarahuka, Luke A1 - Oh, In-Hwan A1 - Ohkubo, Takayoshi A1 - Olusanya, Bolajoko O A1 - Omer, Saad B A1 - Opio, John Nelson A1 - Orozco, Ricardo A1 - Pagcatipunan, Rodolfo S A1 - Pain, Amanda W A1 - Pandian, Jeyaraj D A1 - Panelo, Carlo Irwin A A1 - Papachristou, Christina A1 - Park, Eun-Kee A1 - Parry, Charles D A1 - Paternina Caicedo, Angel J A1 - Patten, Scott B A1 - Paul, Vinod K A1 - Pavlin, Boris I A1 - Pearce, Neil A1 - Pedraza, Lilia S A1 - Pedroza, Andrea A1 - Pejin Stokic, Ljiljana A1 - Pekericli, Ayfer A1 - Pereira, David M A1 - Perez-Padilla, Rogelio A1 - Perez-Ruiz, Fernando A1 - Perico, Norberto A1 - Perry, Samuel A L A1 - Pervaiz, Aslam A1 - Pesudovs, Konrad A1 - Peterson, Carrie B A1 - Petzold, Max A1 - Phillips, Michael R A1 - Phua, Hwee Pin A1 - Plass, Dietrich A1 - Poenaru, Dan A1 - Polanczyk, Guilherme V A1 - Polinder, Suzanne A1 - Pond, Constance D A1 - Pope, C Arden A1 - Pope, Daniel A1 - Popova, Svetlana A1 - Pourmalek, Farshad A1 - Powles, John A1 - Prabhakaran, Dorairaj A1 - Prasad, Noela M A1 - Qato, Dima M A1 - Quezada, Amado D A1 - Quistberg, D Alex A A1 - Racapé, Lionel A1 - Rafay, Anwar A1 - Rahimi, Kazem A1 - Rahimi-Movaghar, Vafa A1 - Rahman, Sajjad Ur A1 - Raju, Murugesan A1 - Rakovac, Ivo A1 - Rana, Saleem M A1 - Rao, Mayuree A1 - Razavi, Homie A1 - Reddy, K Srinath A1 - Refaat, Amany H A1 - Rehm, Jürgen A1 - Remuzzi, Giuseppe A1 - Ribeiro, Antonio L A1 - Riccio, Patricia M A1 - Richardson, Lee A1 - Riederer, Anne A1 - Robinson, Margaret A1 - Roca, Anna A1 - Rodriguez, Alina A1 - Rojas-Rueda, David A1 - Romieu, Isabelle A1 - Ronfani, Luca A1 - Room, Robin A1 - Roy, Nobhojit A1 - Ruhago, George M A1 - Rushton, Lesley A1 - Sabin, Nsanzimana A1 - Sacco, Ralph L A1 - Saha, Sukanta A1 - Sahathevan, Ramesh A1 - Sahraian, Mohammad Ali A1 - Salomon, Joshua A A1 - Salvo, Deborah A1 - Sampson, Uchechukwu K A1 - Sanabria, Juan R A1 - Sanchez, Luz Maria A1 - Sánchez-Pimienta, Tania G A1 - Sanchez-Riera, Lidia A1 - Sandar, Logan A1 - Santos, Itamar S A1 - Sapkota, Amir A1 - Satpathy, Maheswar A1 - Saunders, James E A1 - Sawhney, Monika A1 - Saylan, Mete I A1 - Scarborough, Peter A1 - Schmidt, Jürgen C A1 - Schneider, Ione J C A1 - Schöttker, Ben A1 - Schwebel, David C A1 - Scott, James G A1 - Seedat, Soraya A1 - Sepanlou, Sadaf G A1 - Serdar, Berrin A1 - Servan-Mori, Edson E A1 - Shaddick, Gavin A1 - Shahraz, Saeid A1 - Levy, Teresa Shamah A1 - Shangguan, Siyi A1 - She, Jun A1 - Sheikhbahaei, Sara A1 - Shibuya, Kenji A1 - Shin, Hwashin H A1 - Shinohara, Yukito A1 - Shiri, Rahman A1 - Shishani, Kawkab A1 - Shiue, Ivy A1 - Sigfusdottir, Inga D A1 - Silberberg, Donald H A1 - Simard, Edgar P A1 - Sindi, Shireen A1 - Singh, Abhishek A1 - Singh, Gitanjali M A1 - Singh, Jasvinder A A1 - Skirbekk, Vegard A1 - Sliwa, Karen A1 - Soljak, Michael A1 - Soneji, Samir A1 - Søreide, Kjetil A1 - Soshnikov, Sergey A1 - Sposato, Luciano A A1 - Sreeramareddy, Chandrashekhar T A1 - Stapelberg, Nicolas J C A1 - Stathopoulou, Vasiliki A1 - Steckling, Nadine A1 - Stein, Dan J A1 - Stein, Murray B A1 - Stephens, Natalie A1 - Stöckl, Heidi A1 - Straif, Kurt A1 - Stroumpoulis, Konstantinos A1 - Sturua, Lela A1 - Sunguya, Bruno F A1 - Swaminathan, Soumya A1 - Swaroop, Mamta A1 - Sykes, Bryan L A1 - Tabb, Karen M A1 - Takahashi, Ken A1 - Talongwa, Roberto T A1 - Tandon, Nikhil A1 - Tanne, David A1 - Tanner, Marcel A1 - Tavakkoli, Mohammad A1 - Te Ao, Braden J A1 - Teixeira, Carolina M A1 - Téllez Rojo, Martha M A1 - Terkawi, Abdullah S A1 - Texcalac-Sangrador, José Luis A1 - Thackway, Sarah V A1 - Thomson, Blake A1 - Thorne-Lyman, Andrew L A1 - Thrift, Amanda G A1 - Thurston, George D A1 - Tillmann, Taavi A1 - Tobollik, Myriam A1 - Tonelli, Marcello A1 - Topouzis, Fotis A1 - Towbin, Jeffrey A A1 - Toyoshima, Hideaki A1 - Traebert, Jefferson A1 - Tran, Bach X A1 - Trasande, Leonardo A1 - Trillini, Matias A1 - Trujillo, Ulises A1 - Dimbuene, Zacharie Tsala A1 - Tsilimbaris, Miltiadis A1 - Tuzcu, Emin Murat A1 - Uchendu, Uche S A1 - Ukwaja, Kingsley N A1 - Uzun, Selen B A1 - van de Vijver, Steven A1 - Van Dingenen, Rita A1 - van Gool, Coen H A1 - van Os, Jim A1 - Varakin, Yuri Y A1 - Vasankari, Tommi J A1 - Vasconcelos, Ana Maria N A1 - Vavilala, Monica S A1 - Veerman, Lennert J A1 - Velasquez-Melendez, Gustavo A1 - Venketasubramanian, N A1 - Vijayakumar, Lakshmi A1 - Villalpando, Salvador A1 - Violante, Francesco S A1 - Vlassov, Vasiliy Victorovich A1 - Vollset, Stein Emil A1 - Wagner, Gregory R A1 - Waller, Stephen G A1 - Wallin, Mitchell T A1 - Wan, Xia A1 - Wang, Haidong A1 - Wang, JianLi A1 - Wang, Linhong A1 - Wang, Wenzhi A1 - Wang, Yanping A1 - Warouw, Tati S A1 - Watts, Charlotte H A1 - Weichenthal, Scott A1 - Weiderpass, Elisabete A1 - Weintraub, Robert G A1 - Werdecker, Andrea A1 - Wessells, K Ryan A1 - Westerman, Ronny A1 - Whiteford, Harvey A A1 - Wilkinson, James D A1 - Williams, Hywel C A1 - Williams, Thomas N A1 - Woldeyohannes, Solomon M A1 - Wolfe, Charles D A A1 - Wong, John Q A1 - Woolf, Anthony D A1 - Wright, Jonathan L A1 - Wurtz, Brittany A1 - Xu, Gelin A1 - Yan, Lijing L A1 - Yang, Gonghuan A1 - Yano, Yuichiro A1 - Ye, Pengpeng A1 - Yenesew, Muluken A1 - Yentür, Gökalp K A1 - Yip, Paul A1 - Yonemoto, Naohiro A1 - Yoon, Seok-Jun A1 - Younis, Mustafa Z A1 - Younoussi, Zourkaleini A1 - Yu, Chuanhua A1 - Zaki, Maysaa E A1 - Zhao, Yong A1 - Zheng, Yingfeng A1 - Zhou, Maigeng A1 - Zhu, Jun A1 - Zhu, Shankuan A1 - Zou, Xiaonong A1 - Zunt, Joseph R A1 - Lopez, Alan D A1 - Vos, Theo A1 - Murray, Christopher J AB -

BACKGROUND: The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution.

METHODS: Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk-outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990-2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian meta-regression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol.

FINDINGS: All risks combined account for 57·2% (95% uncertainty interval [UI] 55·8-58·5) of deaths and 41·6% (40·1-43·0) of DALYs. Risks quantified account for 87·9% (86·5-89·3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11·3 million deaths and 241·4 million DALYs, high systolic blood pressure for 10·4 million deaths and 208·1 million DALYs, child and maternal malnutrition for 1·7 million deaths and 176·9 million DALYs, tobacco smoke for 6·1 million deaths and 143·5 million DALYs, air pollution for 5·5 million deaths and 141·5 million DALYs, and high BMI for 4·4 million deaths and 134·0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa.

INTERPRETATION: Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks.

FUNDING: Bill & Melinda Gates Foundation.

VL - 386 IS - 10010 U1 - http://www.ncbi.nlm.nih.gov/pubmed/26364544?dopt=Abstract ER - TY - JOUR T1 - Global, regional, and national disability-adjusted life years (DALYs) for 306 diseases and injuries and healthy life expectancy (HALE) for 188 countries, 1990-2013: quantifying the epidemiological transition. JF - Lancet Y1 - 2015 A1 - Murray, Christopher J L A1 - Barber, Ryan M A1 - Foreman, Kyle J A1 - Abbasoglu Ozgoren, Ayse A1 - Abd-Allah, Foad A1 - Abera, Semaw F A1 - Aboyans, Victor A1 - Abraham, Jerry P A1 - Abubakar, Ibrahim A1 - Abu-Raddad, Laith J A1 - Abu-Rmeileh, Niveen M A1 - Achoki, Tom A1 - Ackerman, Ilana N A1 - Ademi, Zanfina A1 - Adou, Arsène K A1 - Adsuar, José C A1 - Afshin, Ashkan A1 - Agardh, Emilie E A1 - Alam, Sayed Saidul A1 - Alasfoor, Deena A1 - Albittar, Mohammed I A1 - Alegretti, Miguel A A1 - Alemu, Zewdie A A1 - Alfonso-Cristancho, Rafael A1 - Alhabib, Samia A1 - Ali, Raghib A1 - Alla, François A1 - Allebeck, Peter A1 - AlMazroa, Mohammad A A1 - Alsharif, Ubai A1 - Alvarez, Elena A1 - Alvis-Guzmán, Nelson A1 - Amare, Azmeraw T A1 - Ameh, Emmanuel A A1 - Amini, Heresh A1 - Ammar, Walid A1 - Anderson, H Ross A1 - Anderson, Benjamin O A1 - Antonio, Carl Abelardo T A1 - Anwari, Palwasha A1 - Arnlöv, Johan A1 - Arsic Arsenijevic, Valentina S A1 - Artaman, Al A1 - Asghar, Rana J A1 - Assadi, Reza A1 - Atkins, Lydia S A1 - Avila, Marco A A1 - Awuah, Baffour A1 - Bachman, Victoria F A1 - Badawi, Alaa A1 - Bahit, Maria C A1 - Balakrishnan, Kalpana A1 - Banerjee, Amitava A1 - Barker-Collo, Suzanne L A1 - Barquera, Simon A1 - Barregard, Lars A1 - Barrero, Lope H A1 - Basu, Arindam A1 - Basu, Sanjay A1 - Basulaiman, Mohammed O A1 - Beardsley, Justin A1 - Bedi, Neeraj A1 - Beghi, Ettore A1 - Bekele, Tolesa A1 - Bell, Michelle L A1 - Benjet, Corina A1 - Bennett, Derrick A A1 - Bensenor, Isabela M A1 - Benzian, Habib A1 - Bernabe, Eduardo A1 - Bertozzi-Villa, Amelia A1 - Beyene, Tariku J A1 - Bhala, Neeraj A1 - Bhalla, Ashish A1 - Bhutta, Zulfiqar A A1 - Bienhoff, Kelly A1 - Bikbov, Boris A1 - Biryukov, Stan A1 - Blore, Jed D A1 - Blosser, Christopher D A1 - Blyth, Fiona M A1 - Bohensky, Megan A A1 - Bolliger, Ian W A1 - Bora Başara, Berrak A1 - Bornstein, Natan M A1 - Bose, Dipan A1 - Boufous, Soufiane A1 - Bourne, Rupert R A A1 - Boyers, Lindsay N A1 - Brainin, Michael A1 - Brayne, Carol E A1 - Brazinova, Alexandra A1 - Breitborde, Nicholas J K A1 - Brenner, Hermann A1 - Briggs, Adam D A1 - Brooks, Peter M A1 - Brown, Jonathan C A1 - Brugha, Traolach S A1 - Buchbinder, Rachelle A1 - Buckle, Geoffrey C A1 - Budke, Christine M A1 - Bulchis, Anne A1 - Bulloch, Andrew G A1 - Campos-Nonato, Ismael R A1 - Carabin, Hélène A1 - Carapetis, Jonathan R A1 - Cárdenas, Rosario A1 - Carpenter, David O A1 - Caso, Valeria A1 - Castañeda-Orjuela, Carlos A A1 - Castro, Ruben E A1 - Catalá-López, Ferrán A1 - Cavalleri, Fiorella A1 - Cavlin, Alanur A1 - Chadha, Vineet K A1 - Chang, Jung-Chen A1 - Charlson, Fiona J A1 - Chen, Honglei A1 - Chen, Wanqing A1 - Chiang, Peggy P A1 - Chimed-Ochir, Odgerel A1 - Chowdhury, Rajiv A1 - Christensen, Hanne A1 - Christophi, Costas A A1 - Cirillo, Massimo A1 - Coates, Matthew M A1 - Coffeng, Luc E A1 - Coggeshall, Megan S A1 - Colistro, Valentina A1 - Colquhoun, Samantha M A1 - Cooke, Graham S A1 - Cooper, Cyrus A1 - Cooper, Leslie T A1 - Coppola, Luis M A1 - Cortinovis, Monica A1 - Criqui, Michael H A1 - Crump, John A A1 - Cuevas-Nasu, Lucia A1 - Danawi, Hadi A1 - Dandona, Lalit A1 - Dandona, Rakhi A1 - Dansereau, Emily A1 - Dargan, Paul I A1 - Davey, Gail A1 - Davis, Adrian A1 - Davitoiu, Dragos V A1 - Dayama, Anand A1 - De Leo, Diego A1 - Degenhardt, Louisa A1 - del Pozo-Cruz, Borja A1 - Dellavalle, Robert P A1 - Deribe, Kebede A1 - Derrett, Sarah A1 - Des Jarlais, Don C A1 - Dessalegn, Muluken A1 - Dharmaratne, Samath D A1 - Dherani, Mukesh K A1 - Diaz-Torné, Cesar A1 - Dicker, Daniel A1 - Ding, Eric L A1 - Dokova, Klara A1 - Dorsey, E Ray A1 - Driscoll, Tim R A1 - Duan, Leilei A1 - Duber, Herbert C A1 - Ebel, Beth E A1 - Edmond, Karen M A1 - Elshrek, Yousef M A1 - Endres, Matthias A1 - Ermakov, Sergey P A1 - Erskine, Holly E A1 - Eshrati, Babak A1 - Esteghamati, Alireza A1 - Estep, Kara A1 - Faraon, Emerito Jose A A1 - Farzadfar, Farshad A1 - Fay, Derek F A1 - Feigin, Valery L A1 - Felson, David T A1 - Fereshtehnejad, Seyed-Mohammad A1 - Fernandes, Jefferson G A1 - Ferrari, Alize J A1 - Fitzmaurice, Christina A1 - Flaxman, Abraham D A1 - Fleming, Thomas D A1 - Foigt, Nataliya A1 - Forouzanfar, Mohammad H A1 - Fowkes, F Gerry R A1 - Paleo, Urbano Fra A1 - Franklin, Richard C A1 - Fürst, Thomas A1 - Gabbe, Belinda A1 - Gaffikin, Lynne A1 - Gankpé, Fortuné G A1 - Geleijnse, Johanna M A1 - Gessner, Bradford D A1 - Gething, Peter A1 - Gibney, Katherine B A1 - Giroud, Maurice A1 - Giussani, Giorgia A1 - Gomez Dantes, Hector A1 - Gona, Philimon A1 - Gonzalez-Medina, Diego A1 - Gosselin, Richard A A1 - Gotay, Carolyn C A1 - Goto, Atsushi A1 - Gouda, Hebe N A1 - Graetz, Nicholas A1 - Gugnani, Harish C A1 - Gupta, Rahul A1 - Gupta, Rajeev A1 - Gutiérrez, Reyna A A1 - Haagsma, Juanita A1 - Hafezi-Nejad, Nima A1 - Hagan, Holly A1 - Halasa, Yara A A1 - Hamadeh, Randah R A1 - Hamavid, Hannah A1 - Hammami, Mouhanad A1 - Hancock, Jamie A1 - Hankey, Graeme J A1 - Hansen, Gillian M A1 - Hao, Yuantao A1 - Harb, Hilda L A1 - Haro, Josep Maria A1 - Havmoeller, Rasmus A1 - Hay, Simon I A1 - Hay, Roderick J A1 - Heredia-Pi, Ileana B A1 - Heuton, Kyle R A1 - Heydarpour, Pouria A1 - Higashi, Hideki A1 - Hijar, Martha A1 - Hoek, Hans W A1 - Hoffman, Howard J A1 - Hosgood, H Dean A1 - Hossain, Mazeda A1 - Hotez, Peter J A1 - Hoy, Damian G A1 - Hsairi, Mohamed A1 - Hu, Guoqing A1 - Huang, Cheng A1 - Huang, John J A1 - Husseini, Abdullatif A1 - Huynh, Chantal A1 - Iannarone, Marissa L A1 - Iburg, Kim M A1 - Innos, Kaire A1 - Inoue, Manami A1 - Islami, Farhad A1 - Jacobsen, Kathryn H A1 - Jarvis, Deborah L A1 - Jassal, Simerjot K A1 - Jee, Sun Ha A1 - Jeemon, Panniyammakal A1 - Jensen, Paul N A1 - Jha, Vivekanand A1 - Jiang, Guohong A1 - Jiang, Ying A1 - Jonas, Jost B A1 - Juel, Knud A1 - Kan, Haidong A1 - Karch, André A1 - Karema, Corine K A1 - Karimkhani, Chante A1 - Karthikeyan, Ganesan A1 - Kassebaum, Nicholas J A1 - Kaul, Anil A1 - Kawakami, Norito A1 - Kazanjan, Konstantin A1 - Kemp, Andrew H A1 - Kengne, Andre P A1 - Keren, Andre A1 - Khader, Yousef S A1 - Khalifa, Shams Eldin A A1 - Khan, Ejaz A A1 - Khan, Gulfaraz A1 - Khang, Young-Ho A1 - Kieling, Christian A1 - Kim, Daniel A1 - Kim, Sungroul A1 - Kim, Yunjin A1 - Kinfu, Yohannes A1 - Kinge, Jonas M A1 - Kivipelto, Miia A1 - Knibbs, Luke D A1 - Knudsen, Ann Kristin A1 - Kokubo, Yoshihiro A1 - Kosen, Soewarta A1 - Krishnaswami, Sanjay A1 - Kuate Defo, Barthelemy A1 - Kucuk Bicer, Burcu A1 - Kuipers, Ernst J A1 - Kulkarni, Chanda A1 - Kulkarni, Veena S A1 - Kumar, G Anil A1 - Kyu, Hmwe H A1 - Lai, Taavi A1 - Lalloo, Ratilal A1 - Lallukka, Tea A1 - Lam, Hilton A1 - Lan, Qing A1 - Lansingh, Van C A1 - Larsson, Anders A1 - Lawrynowicz, Alicia E B A1 - Leasher, Janet L A1 - Leigh, James A1 - Leung, Ricky A1 - Levitz, Carly E A1 - Li, Bin A1 - Li, Yichong A1 - Li, Yongmei A1 - Lim, Stephen S A1 - Lind, Maggie A1 - Lipshultz, Steven E A1 - Liu, Shiwei A1 - Liu, Yang A1 - Lloyd, Belinda K A1 - Lofgren, Katherine T A1 - Logroscino, Giancarlo A1 - Looker, Katharine J A1 - Lortet-Tieulent, Joannie A1 - Lotufo, Paulo A A1 - Lozano, Rafael A1 - Lucas, Robyn M A1 - Lunevicius, Raimundas A1 - Lyons, Ronan A A1 - Ma, Stefan A1 - MacIntyre, Michael F A1 - Mackay, Mark T A1 - Majdan, Marek A1 - Malekzadeh, Reza A1 - Marcenes, Wagner A1 - Margolis, David J A1 - Margono, Christopher A1 - Marzan, Melvin B A1 - Masci, Joseph R A1 - Mashal, Mohammad T A1 - Matzopoulos, Richard A1 - Mayosi, Bongani M A1 - Mazorodze, Tasara T A1 - Mcgill, Neil W A1 - McGrath, John J A1 - McKee, Martin A1 - McLain, Abigail A1 - Meaney, Peter A A1 - Medina, Catalina A1 - Mehndiratta, Man Mohan A1 - Mekonnen, Wubegzier A1 - Melaku, Yohannes A A1 - Meltzer, Michele A1 - Memish, Ziad A A1 - Mensah, George A A1 - Meretoja, Atte A1 - Mhimbira, Francis A A1 - Micha, Renata A1 - Miller, Ted R A1 - Mills, Edward J A1 - Mitchell, Philip B A1 - Mock, Charles N A1 - Mohamed Ibrahim, Norlinah A1 - Mohammad, Karzan A A1 - Mokdad, Ali H A1 - Mola, Glen L D A1 - Monasta, Lorenzo A1 - Montañez Hernandez, Julio C A1 - Montico, Marcella A1 - Montine, Thomas J A1 - Mooney, Meghan D A1 - Moore, Ami R A1 - Moradi-Lakeh, Maziar A1 - Moran, Andrew E A1 - Mori, Rintaro A1 - Moschandreas, Joanna A1 - Moturi, Wilkister N A1 - Moyer, Madeline L A1 - Mozaffarian, Dariush A1 - Msemburi, William T A1 - Mueller, Ulrich O A1 - Mukaigawara, Mitsuru A1 - Mullany, Erin C A1 - Murdoch, Michele E A1 - Murray, Joseph A1 - Murthy, Kinnari S A1 - Naghavi, Mohsen A1 - Naheed, Aliya A1 - Naidoo, Kovin S A1 - Naldi, Luigi A1 - Nand, Devina A1 - Nangia, Vinay A1 - Narayan, K M Venkat A1 - Nejjari, Chakib A1 - Neupane, Sudan P A1 - Newton, Charles R A1 - Ng, Marie A1 - Ngalesoni, Frida N A1 - Nguyen, Grant A1 - Nisar, Muhammad I A1 - Nolte, Sandra A1 - Norheim, Ole F A1 - Norman, Rosana E A1 - Norrving, Bo A1 - Nyakarahuka, Luke A1 - Oh, In-Hwan A1 - Ohkubo, Takayoshi A1 - Ohno, Summer L A1 - Olusanya, Bolajoko O A1 - Opio, John Nelson A1 - Ortblad, Katrina A1 - Ortiz, Alberto A1 - Pain, Amanda W A1 - Pandian, Jeyaraj D A1 - Panelo, Carlo Irwin A A1 - Papachristou, Christina A1 - Park, Eun-Kee A1 - Park, Jae-Hyun A1 - Patten, Scott B A1 - Patton, George C A1 - Paul, Vinod K A1 - Pavlin, Boris I A1 - Pearce, Neil A1 - Pereira, David M A1 - Perez-Padilla, Rogelio A1 - Perez-Ruiz, Fernando A1 - Perico, Norberto A1 - Pervaiz, Aslam A1 - Pesudovs, Konrad A1 - Peterson, Carrie B A1 - Petzold, Max A1 - Phillips, Michael R A1 - Phillips, Bryan K A1 - Phillips, David E A1 - Piel, Frédéric B A1 - Plass, Dietrich A1 - Poenaru, Dan A1 - Polinder, Suzanne A1 - Pope, Daniel A1 - Popova, Svetlana A1 - Poulton, Richie G A1 - Pourmalek, Farshad A1 - Prabhakaran, Dorairaj A1 - Prasad, Noela M A1 - Pullan, Rachel L A1 - Qato, Dima M A1 - Quistberg, D Alex A1 - Rafay, Anwar A1 - Rahimi, Kazem A1 - Rahman, Sajjad U A1 - Raju, Murugesan A1 - Rana, Saleem M A1 - Razavi, Homie A1 - Reddy, K Srinath A1 - Refaat, Amany A1 - Remuzzi, Giuseppe A1 - Resnikoff, Serge A1 - Ribeiro, Antonio L A1 - Richardson, Lee A1 - Richardus, Jan Hendrik A1 - Roberts, D Allen A1 - Rojas-Rueda, David A1 - Ronfani, Luca A1 - Roth, Gregory A A1 - Rothenbacher, Dietrich A1 - Rothstein, David H A1 - Rowley, Jane T A1 - Roy, Nobhojit A1 - Ruhago, George M A1 - Saeedi, Mohammad Y A1 - Saha, Sukanta A1 - Sahraian, Mohammad Ali A1 - Sampson, Uchechukwu K A A1 - Sanabria, Juan R A1 - Sandar, Logan A1 - Santos, Itamar S A1 - Satpathy, Maheswar A1 - Sawhney, Monika A1 - Scarborough, Peter A1 - Schneider, Ione J A1 - Schöttker, Ben A1 - Schumacher, Austin E A1 - Schwebel, David C A1 - Scott, James G A1 - Seedat, Soraya A1 - Sepanlou, Sadaf G A1 - Serina, Peter T A1 - Servan-Mori, Edson E A1 - Shackelford, Katya A A1 - Shaheen, Amira A1 - Shahraz, Saeid A1 - Shamah Levy, Teresa A1 - Shangguan, Siyi A1 - She, Jun A1 - Sheikhbahaei, Sara A1 - Shi, Peilin A1 - Shibuya, Kenji A1 - Shinohara, Yukito A1 - Shiri, Rahman A1 - Shishani, Kawkab A1 - Shiue, Ivy A1 - Shrime, Mark G A1 - Sigfusdottir, Inga D A1 - Silberberg, Donald H A1 - Simard, Edgar P A1 - Sindi, Shireen A1 - Singh, Abhishek A1 - Singh, Jasvinder A A1 - Singh, Lavanya A1 - Skirbekk, Vegard A1 - Slepak, Erica Leigh A1 - Sliwa, Karen A1 - Soneji, Samir A1 - Søreide, Kjetil A1 - Soshnikov, Sergey A1 - Sposato, Luciano A A1 - Sreeramareddy, Chandrashekhar T A1 - Stanaway, Jeffrey D A1 - Stathopoulou, Vasiliki A1 - Stein, Dan J A1 - Stein, Murray B A1 - Steiner, Caitlyn A1 - Steiner, Timothy J A1 - Stevens, Antony A1 - Stewart, Andrea A1 - Stovner, Lars J A1 - Stroumpoulis, Konstantinos A1 - Sunguya, Bruno F A1 - Swaminathan, Soumya A1 - Swaroop, Mamta A1 - Sykes, Bryan L A1 - Tabb, Karen M A1 - Takahashi, Ken A1 - Tandon, Nikhil A1 - Tanne, David A1 - Tanner, Marcel A1 - Tavakkoli, Mohammad A1 - Taylor, Hugh R A1 - Te Ao, Braden J A1 - Tediosi, Fabrizio A1 - Temesgen, Awoke M A1 - Templin, Tara A1 - Ten Have, Margreet A1 - Tenkorang, Eric Y A1 - Terkawi, Abdullah S A1 - Thomson, Blake A1 - Thorne-Lyman, Andrew L A1 - Thrift, Amanda G A1 - Thurston, George D A1 - Tillmann, Taavi A1 - Tonelli, Marcello A1 - Topouzis, Fotis A1 - Toyoshima, Hideaki A1 - Traebert, Jefferson A1 - Tran, Bach X A1 - Trillini, Matias A1 - Truelsen, Thomas A1 - Tsilimbaris, Miltiadis A1 - Tuzcu, Emin M A1 - Uchendu, Uche S A1 - Ukwaja, Kingsley N A1 - Undurraga, Eduardo A A1 - Uzun, Selen B A1 - Van Brakel, Wim H A1 - van de Vijver, Steven A1 - van Gool, Coen H A1 - van Os, Jim A1 - Vasankari, Tommi J A1 - Venketasubramanian, N A1 - Violante, Francesco S A1 - Vlassov, Vasiliy V A1 - Vollset, Stein Emil A1 - Wagner, Gregory R A1 - Wagner, Joseph A1 - Waller, Stephen G A1 - Wan, Xia A1 - Wang, Haidong A1 - Wang, JianLi A1 - Wang, Linhong A1 - Warouw, Tati S A1 - Weichenthal, Scott A1 - Weiderpass, Elisabete A1 - Weintraub, Robert G A1 - Wenzhi, Wang A1 - Werdecker, Andrea A1 - Westerman, Ronny A1 - Whiteford, Harvey A A1 - Wilkinson, James D A1 - Williams, Thomas N A1 - Wolfe, Charles D A1 - Wolock, Timothy M A1 - Woolf, Anthony D A1 - Wulf, Sarah A1 - Wurtz, Brittany A1 - Xu, Gelin A1 - Yan, Lijing L A1 - Yano, Yuichiro A1 - Ye, Pengpeng A1 - Yentür, Gökalp K A1 - Yip, Paul A1 - Yonemoto, Naohiro A1 - Yoon, Seok-Jun A1 - Younis, Mustafa Z A1 - Yu, Chuanhua A1 - Zaki, Maysaa E A1 - Zhao, Yong A1 - Zheng, Yingfeng A1 - Zonies, David A1 - Zou, Xiaonong A1 - Salomon, Joshua A A1 - Lopez, Alan D A1 - Vos, Theo KW - Aged KW - Chronic Disease KW - Communicable Diseases KW - Female KW - Global Health KW - Health Transition KW - Humans KW - Life Expectancy KW - Male KW - Middle Aged KW - Mortality, Premature KW - Quality-Adjusted Life Years KW - Socioeconomic Factors KW - Wounds and Injuries AB -

BACKGROUND: The Global Burden of Disease Study 2013 (GBD 2013) aims to bring together all available epidemiological data using a coherent measurement framework, standardised estimation methods, and transparent data sources to enable comparisons of health loss over time and across causes, age-sex groups, and countries. The GBD can be used to generate summary measures such as disability-adjusted life-years (DALYs) and healthy life expectancy (HALE) that make possible comparative assessments of broad epidemiological patterns across countries and time. These summary measures can also be used to quantify the component of variation in epidemiology that is related to sociodemographic development.

METHODS: We used the published GBD 2013 data for age-specific mortality, years of life lost due to premature mortality (YLLs), and years lived with disability (YLDs) to calculate DALYs and HALE for 1990, 1995, 2000, 2005, 2010, and 2013 for 188 countries. We calculated HALE using the Sullivan method; 95% uncertainty intervals (UIs) represent uncertainty in age-specific death rates and YLDs per person for each country, age, sex, and year. We estimated DALYs for 306 causes for each country as the sum of YLLs and YLDs; 95% UIs represent uncertainty in YLL and YLD rates. We quantified patterns of the epidemiological transition with a composite indicator of sociodemographic status, which we constructed from income per person, average years of schooling after age 15 years, and the total fertility rate and mean age of the population. We applied hierarchical regression to DALY rates by cause across countries to decompose variance related to the sociodemographic status variable, country, and time.

FINDINGS: Worldwide, from 1990 to 2013, life expectancy at birth rose by 6·2 years (95% UI 5·6-6·6), from 65·3 years (65·0-65·6) in 1990 to 71·5 years (71·0-71·9) in 2013, HALE at birth rose by 5·4 years (4·9-5·8), from 56·9 years (54·5-59·1) to 62·3 years (59·7-64·8), total DALYs fell by 3·6% (0·3-7·4), and age-standardised DALY rates per 100 000 people fell by 26·7% (24·6-29·1). For communicable, maternal, neonatal, and nutritional disorders, global DALY numbers, crude rates, and age-standardised rates have all declined between 1990 and 2013, whereas for non-communicable diseases, global DALYs have been increasing, DALY rates have remained nearly constant, and age-standardised DALY rates declined during the same period. From 2005 to 2013, the number of DALYs increased for most specific non-communicable diseases, including cardiovascular diseases and neoplasms, in addition to dengue, food-borne trematodes, and leishmaniasis; DALYs decreased for nearly all other causes. By 2013, the five leading causes of DALYs were ischaemic heart disease, lower respiratory infections, cerebrovascular disease, low back and neck pain, and road injuries. Sociodemographic status explained more than 50% of the variance between countries and over time for diarrhoea, lower respiratory infections, and other common infectious diseases; maternal disorders; neonatal disorders; nutritional deficiencies; other communicable, maternal, neonatal, and nutritional diseases; musculoskeletal disorders; and other non-communicable diseases. However, sociodemographic status explained less than 10% of the variance in DALY rates for cardiovascular diseases; chronic respiratory diseases; cirrhosis; diabetes, urogenital, blood, and endocrine diseases; unintentional injuries; and self-harm and interpersonal violence. Predictably, increased sociodemographic status was associated with a shift in burden from YLLs to YLDs, driven by declines in YLLs and increases in YLDs from musculoskeletal disorders, neurological disorders, and mental and substance use disorders. In most country-specific estimates, the increase in life expectancy was greater than that in HALE. Leading causes of DALYs are highly variable across countries.

INTERPRETATION: Global health is improving. Population growth and ageing have driven up numbers of DALYs, but crude rates have remained relatively constant, showing that progress in health does not mean fewer demands on health systems. The notion of an epidemiological transition--in which increasing sociodemographic status brings structured change in disease burden--is useful, but there is tremendous variation in burden of disease that is not associated with sociodemographic status. This further underscores the need for country-specific assessments of DALYs and HALE to appropriately inform health policy decisions and attendant actions.

FUNDING: Bill & Melinda Gates Foundation.

VL - 386 IS - 10009 U1 - http://www.ncbi.nlm.nih.gov/pubmed/26321261?dopt=Abstract ER - TY - JOUR T1 - Large-scale genomic analyses link reproductive aging to hypothalamic signaling, breast cancer susceptibility and BRCA1-mediated DNA repair. JF - Nat Genet Y1 - 2015 A1 - Day, Felix R A1 - Ruth, Katherine S A1 - Thompson, Deborah J A1 - Lunetta, Kathryn L A1 - Pervjakova, Natalia A1 - Chasman, Daniel I A1 - Stolk, Lisette A1 - Finucane, Hilary K A1 - Sulem, Patrick A1 - Bulik-Sullivan, Brendan A1 - Esko, Tõnu A1 - Johnson, Andrew D A1 - Elks, Cathy E A1 - Franceschini, Nora A1 - He, Chunyan A1 - Altmaier, Elisabeth A1 - Brody, Jennifer A A1 - Franke, Lude L A1 - Huffman, Jennifer E A1 - Keller, Margaux F A1 - McArdle, Patrick F A1 - Nutile, Teresa A1 - Porcu, Eleonora A1 - Robino, Antonietta A1 - Rose, Lynda M A1 - Schick, Ursula M A1 - Smith, Jennifer A A1 - Teumer, Alexander A1 - Traglia, Michela A1 - Vuckovic, Dragana A1 - Yao, Jie A1 - Zhao, Wei A1 - Albrecht, Eva A1 - Amin, Najaf A1 - Corre, Tanguy A1 - Hottenga, Jouke-Jan A1 - Mangino, Massimo A1 - Smith, Albert V A1 - Tanaka, Toshiko A1 - Abecasis, Goncalo R A1 - Andrulis, Irene L A1 - Anton-Culver, Hoda A1 - Antoniou, Antonis C A1 - Arndt, Volker A1 - Arnold, Alice M A1 - Barbieri, Caterina A1 - Beckmann, Matthias W A1 - Beeghly-Fadiel, Alicia A1 - Benitez, Javier A1 - Bernstein, Leslie A1 - Bielinski, Suzette J A1 - Blomqvist, Carl A1 - Boerwinkle, Eric A1 - Bogdanova, Natalia V A1 - Bojesen, Stig E A1 - Bolla, Manjeet K A1 - Borresen-Dale, Anne-Lise A1 - Boutin, Thibaud S A1 - Brauch, Hiltrud A1 - Brenner, Hermann A1 - Brüning, Thomas A1 - Burwinkel, Barbara A1 - Campbell, Archie A1 - Campbell, Harry A1 - Chanock, Stephen J A1 - Chapman, J Ross A1 - Chen, Yii-Der Ida A1 - Chenevix-Trench, Georgia A1 - Couch, Fergus J A1 - Coviello, Andrea D A1 - Cox, Angela A1 - Czene, Kamila A1 - Darabi, Hatef A1 - De Vivo, Immaculata A1 - Demerath, Ellen W A1 - Dennis, Joe A1 - Devilee, Peter A1 - Dörk, Thilo A1 - Dos-Santos-Silva, Isabel A1 - Dunning, Alison M A1 - Eicher, John D A1 - Fasching, Peter A A1 - Faul, Jessica D A1 - Figueroa, Jonine A1 - Flesch-Janys, Dieter A1 - Gandin, Ilaria A1 - Garcia, Melissa E A1 - García-Closas, Montserrat A1 - Giles, Graham G A1 - Girotto, Giorgia G A1 - Goldberg, Mark S A1 - González-Neira, Anna A1 - Goodarzi, Mark O A1 - Grove, Megan L A1 - Gudbjartsson, Daniel F A1 - Guenel, Pascal A1 - Guo, Xiuqing A1 - Haiman, Christopher A A1 - Hall, Per A1 - Hamann, Ute A1 - Henderson, Brian E A1 - Hocking, Lynne J A1 - Hofman, Albert A1 - Homuth, Georg A1 - Hooning, Maartje J A1 - Hopper, John L A1 - Hu, Frank B A1 - Huang, Jinyan A1 - Humphreys, Keith A1 - Hunter, David J A1 - Jakubowska, Anna A1 - Jones, Samuel E A1 - Kabisch, Maria A1 - Karasik, David A1 - Knight, Julia A A1 - Kolcic, Ivana A1 - Kooperberg, Charles A1 - Kosma, Veli-Matti A1 - Kriebel, Jennifer A1 - Kristensen, Vessela A1 - Lambrechts, Diether A1 - Langenberg, Claudia A1 - Li, Jingmei A1 - Li, Xin A1 - Lindström, Sara A1 - Liu, Yongmei A1 - Luan, Jian'an A1 - Lubinski, Jan A1 - Mägi, Reedik A1 - Mannermaa, Arto A1 - Manz, Judith A1 - Margolin, Sara A1 - Marten, Jonathan A1 - Martin, Nicholas G A1 - Masciullo, Corrado A1 - Meindl, Alfons A1 - Michailidou, Kyriaki A1 - Mihailov, Evelin A1 - Milani, Lili A1 - Milne, Roger L A1 - Müller-Nurasyid, Martina A1 - Nalls, Michael A1 - Neale, Benjamin M A1 - Nevanlinna, Heli A1 - Neven, Patrick A1 - Newman, Anne B A1 - Nordestgaard, Børge G A1 - Olson, Janet E A1 - Padmanabhan, Sandosh A1 - Peterlongo, Paolo A1 - Peters, Ulrike A1 - Petersmann, Astrid A1 - Peto, Julian A1 - Pharoah, Paul D P A1 - Pirastu, Nicola N A1 - Pirie, Ailith A1 - Pistis, Giorgio A1 - Polasek, Ozren A1 - Porteous, David A1 - Psaty, Bruce M A1 - Pylkäs, Katri A1 - Radice, Paolo A1 - Raffel, Leslie J A1 - Rivadeneira, Fernando A1 - Rudan, Igor A1 - Rudolph, Anja A1 - Ruggiero, Daniela A1 - Sala, Cinzia F A1 - Sanna, Serena A1 - Sawyer, Elinor J A1 - Schlessinger, David A1 - Schmidt, Marjanka K A1 - Schmidt, Frank A1 - Schmutzler, Rita K A1 - Schoemaker, Minouk J A1 - Scott, Robert A A1 - Seynaeve, Caroline M A1 - Simard, Jacques A1 - Sorice, Rossella A1 - Southey, Melissa C A1 - Stöckl, Doris A1 - Strauch, Konstantin A1 - Swerdlow, Anthony A1 - Taylor, Kent D A1 - Thorsteinsdottir, Unnur A1 - Toland, Amanda E A1 - Tomlinson, Ian A1 - Truong, Therese A1 - Tryggvadottir, Laufey A1 - Turner, Stephen T A1 - Vozzi, Diego A1 - Wang, Qin A1 - Wellons, Melissa A1 - Willemsen, Gonneke A1 - Wilson, James F A1 - Winqvist, Robert A1 - Wolffenbuttel, Bruce B H R A1 - Wright, Alan F A1 - Yannoukakos, Drakoulis A1 - Zemunik, Tatijana A1 - Zheng, Wei A1 - Zygmunt, Marek A1 - Bergmann, Sven A1 - Boomsma, Dorret I A1 - Buring, Julie E A1 - Ferrucci, Luigi A1 - Montgomery, Grant W A1 - Gudnason, Vilmundur A1 - Spector, Tim D A1 - van Duijn, Cornelia M A1 - Alizadeh, Behrooz Z A1 - Ciullo, Marina A1 - Crisponi, Laura A1 - Easton, Douglas F A1 - Gasparini, Paolo P A1 - Gieger, Christian A1 - Harris, Tamara B A1 - Hayward, Caroline A1 - Kardia, Sharon L R A1 - Kraft, Peter A1 - McKnight, Barbara A1 - Metspalu, Andres A1 - Morrison, Alanna C A1 - Reiner, Alex P A1 - Ridker, Paul M A1 - Rotter, Jerome I A1 - Toniolo, Daniela A1 - Uitterlinden, André G A1 - Ulivi, Sheila A1 - Völzke, Henry A1 - Wareham, Nicholas J A1 - Weir, David R A1 - Yerges-Armstrong, Laura M A1 - Price, Alkes L A1 - Stefansson, Kari A1 - Visser, Jenny A A1 - Ong, Ken K A1 - Chang-Claude, Jenny A1 - Murabito, Joanne M A1 - Perry, John R B A1 - Murray, Anna AB -

Menopause timing has a substantial impact on infertility and risk of disease, including breast cancer, but the underlying mechanisms are poorly understood. We report a dual strategy in ∼70,000 women to identify common and low-frequency protein-coding variation associated with age at natural menopause (ANM). We identified 44 regions with common variants, including two regions harboring additional rare missense alleles of large effect. We found enrichment of signals in or near genes involved in delayed puberty, highlighting the first molecular links between the onset and end of reproductive lifespan. Pathway analyses identified major association with DNA damage response (DDR) genes, including the first common coding variant in BRCA1 associated with any complex trait. Mendelian randomization analyses supported a causal effect of later ANM on breast cancer risk (∼6% increase in risk per year; P = 3 × 10(-14)), likely mediated by prolonged sex hormone exposure rather than DDR mechanisms.

VL - 47 IS - 11 U1 - http://www.ncbi.nlm.nih.gov/pubmed/26414677?dopt=Abstract ER - TY - JOUR T1 - Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche. JF - Nature Y1 - 2014 A1 - Perry, John R B A1 - Day, Felix A1 - Elks, Cathy E A1 - Sulem, Patrick A1 - Thompson, Deborah J A1 - Ferreira, Teresa A1 - He, Chunyan A1 - Chasman, Daniel I A1 - Esko, Tõnu A1 - Thorleifsson, Gudmar A1 - Albrecht, Eva A1 - Ang, Wei Q A1 - Corre, Tanguy A1 - Cousminer, Diana L A1 - Feenstra, Bjarke A1 - Franceschini, Nora A1 - Ganna, Andrea A1 - Johnson, Andrew D A1 - Kjellqvist, Sanela A1 - Lunetta, Kathryn L A1 - McMahon, George A1 - Nolte, Ilja M A1 - Paternoster, Lavinia A1 - Porcu, Eleonora A1 - Smith, Albert V A1 - Stolk, Lisette A1 - Teumer, Alexander A1 - Tšernikova, Natalia A1 - Tikkanen, Emmi A1 - Ulivi, Sheila A1 - Wagner, Erin K A1 - Amin, Najaf A1 - Bierut, Laura J A1 - Byrne, Enda M A1 - Hottenga, Jouke-Jan A1 - Koller, Daniel L A1 - Mangino, Massimo A1 - Pers, Tune H A1 - Yerges-Armstrong, Laura M A1 - Hua Zhao, Jing A1 - Andrulis, Irene L A1 - Anton-Culver, Hoda A1 - Atsma, Femke A1 - Bandinelli, Stefania A1 - Beckmann, Matthias W A1 - Benitez, Javier A1 - Blomqvist, Carl A1 - Bojesen, Stig E A1 - Bolla, Manjeet K A1 - Bonanni, Bernardo A1 - Brauch, Hiltrud A1 - Brenner, Hermann A1 - Buring, Julie E A1 - Chang-Claude, Jenny A1 - Chanock, Stephen A1 - Chen, Jinhui A1 - Chenevix-Trench, Georgia A1 - Collée, J Margriet A1 - Couch, Fergus J A1 - Couper, David A1 - Coviello, Andrea D A1 - Cox, Angela A1 - Czene, Kamila A1 - d'Adamo, Adamo Pio A1 - Davey Smith, George A1 - De Vivo, Immaculata A1 - Demerath, Ellen W A1 - Dennis, Joe A1 - Devilee, Peter A1 - Dieffenbach, Aida K A1 - Dunning, Alison M A1 - Eiriksdottir, Gudny A1 - Eriksson, Johan G A1 - Fasching, Peter A A1 - Ferrucci, Luigi A1 - Flesch-Janys, Dieter A1 - Flyger, Henrik A1 - Foroud, Tatiana A1 - Franke, Lude A1 - Garcia, Melissa E A1 - García-Closas, Montserrat A1 - Geller, Frank A1 - de Geus, Eco E J A1 - Giles, Graham G A1 - Gudbjartsson, Daniel F A1 - Gudnason, Vilmundur A1 - Guenel, Pascal A1 - Guo, Suiqun A1 - Hall, Per A1 - Hamann, Ute A1 - Haring, Robin A1 - Hartman, Catharina A A1 - Heath, Andrew C A1 - Hofman, Albert A1 - Hooning, Maartje J A1 - Hopper, John L A1 - Hu, Frank B A1 - Hunter, David J A1 - Karasik, David A1 - Kiel, Douglas P A1 - Knight, Julia A A1 - Kosma, Veli-Matti A1 - Kutalik, Zoltán A1 - Lai, Sandra A1 - Lambrechts, Diether A1 - Lindblom, Annika A1 - Mägi, Reedik A1 - Magnusson, Patrik K A1 - Mannermaa, Arto A1 - Martin, Nicholas G A1 - Masson, Gisli A1 - McArdle, Patrick F A1 - McArdle, Wendy L A1 - Melbye, Mads A1 - Michailidou, Kyriaki A1 - Mihailov, Evelin A1 - Milani, Lili A1 - Milne, Roger L A1 - Nevanlinna, Heli A1 - Neven, Patrick A1 - Nohr, Ellen A A1 - Oldehinkel, Albertine J A1 - Oostra, Ben A A1 - Palotie, Aarno A1 - Peacock, Munro A1 - Pedersen, Nancy L A1 - Peterlongo, Paolo A1 - Peto, Julian A1 - Pharoah, Paul D P A1 - Postma, Dirkje S A1 - Pouta, Anneli A1 - Pylkäs, Katri A1 - Radice, Paolo A1 - Ring, Susan A1 - Rivadeneira, Fernando A1 - Robino, Antonietta A1 - Rose, Lynda M A1 - Rudolph, Anja A1 - Salomaa, Veikko A1 - Sanna, Serena A1 - Schlessinger, David A1 - Schmidt, Marjanka K A1 - Southey, Mellissa C A1 - Sovio, Ulla A1 - Stampfer, Meir J A1 - Stöckl, Doris A1 - Storniolo, Anna M A1 - Timpson, Nicholas J A1 - Tyrer, Jonathan A1 - Visser, Jenny A A1 - Vollenweider, Peter A1 - Völzke, Henry A1 - Waeber, Gerard A1 - Waldenberger, Melanie A1 - Wallaschofski, Henri A1 - Wang, Qin A1 - Willemsen, Gonneke A1 - Winqvist, Robert A1 - Wolffenbuttel, Bruce H R A1 - Wright, Margaret J A1 - Boomsma, Dorret I A1 - Econs, Michael J A1 - Khaw, Kay-Tee A1 - Loos, Ruth J F A1 - McCarthy, Mark I A1 - Montgomery, Grant W A1 - Rice, John P A1 - Streeten, Elizabeth A A1 - Thorsteinsdottir, Unnur A1 - van Duijn, Cornelia M A1 - Alizadeh, Behrooz Z A1 - Bergmann, Sven A1 - Boerwinkle, Eric A1 - Boyd, Heather A A1 - Crisponi, Laura A1 - Gasparini, Paolo A1 - Gieger, Christian A1 - Harris, Tamara B A1 - Ingelsson, Erik A1 - Järvelin, Marjo-Riitta A1 - Kraft, Peter A1 - Lawlor, Debbie A1 - Metspalu, Andres A1 - Pennell, Craig E A1 - Ridker, Paul M A1 - Snieder, Harold A1 - Sørensen, Thorkild I A A1 - Spector, Tim D A1 - Strachan, David P A1 - Uitterlinden, André G A1 - Wareham, Nicholas J A1 - Widen, Elisabeth A1 - Zygmunt, Marek A1 - Murray, Anna A1 - Easton, Douglas F A1 - Stefansson, Kari A1 - Murabito, Joanne M A1 - Ong, Ken K KW - Adolescent KW - Age Factors KW - Alleles KW - Body Mass Index KW - Breast Neoplasms KW - Cardiovascular Diseases KW - Child KW - Diabetes Mellitus, Type 2 KW - Europe KW - Female KW - Genetic Loci KW - Genome-Wide Association Study KW - Genomic Imprinting KW - Humans KW - Hypothalamo-Hypophyseal System KW - Intercellular Signaling Peptides and Proteins KW - Male KW - Membrane Proteins KW - Menarche KW - Obesity KW - Ovary KW - Parents KW - Polymorphism, Single Nucleotide KW - Potassium Channels, Tandem Pore Domain KW - Proteins KW - Quantitative Trait Loci KW - Receptors, GABA-B KW - Receptors, Retinoic Acid KW - Ribonucleoproteins AB -

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition.

VL - 514 IS - 7520 U1 - http://www.ncbi.nlm.nih.gov/pubmed/25231870?dopt=Abstract ER -