TY - JOUR T1 - Genome-wide association analysis identifies novel blood pressure loci and offers biological insights into cardiovascular risk. JF - Nat Genet Y1 - 2017 A1 - Warren, Helen R A1 - Evangelou, Evangelos A1 - Cabrera, Claudia P A1 - Gao, He A1 - Ren, Meixia A1 - Mifsud, Borbala A1 - Ntalla, Ioanna A1 - Surendran, Praveen A1 - Liu, Chunyu A1 - Cook, James P A1 - Kraja, Aldi T A1 - Drenos, Fotios A1 - Loh, Marie A1 - Verweij, Niek A1 - Marten, Jonathan A1 - Karaman, Ibrahim A1 - Lepe, Marcelo P Segura A1 - O'Reilly, Paul F A1 - Knight, Joanne A1 - Snieder, Harold A1 - Kato, Norihiro A1 - He, Jiang A1 - Tai, E Shyong A1 - Said, M Abdullah A1 - Porteous, David A1 - Alver, Maris A1 - Poulter, Neil A1 - Farrall, Martin A1 - Gansevoort, Ron T A1 - Padmanabhan, Sandosh A1 - Mägi, Reedik A1 - Stanton, Alice A1 - Connell, John A1 - Bakker, Stephan J L A1 - Metspalu, Andres A1 - Shields, Denis C A1 - Thom, Simon A1 - Brown, Morris A1 - Sever, Peter A1 - Esko, Tõnu A1 - Hayward, Caroline A1 - van der Harst, Pim A1 - Saleheen, Danish A1 - Chowdhury, Rajiv A1 - Chambers, John C A1 - Chasman, Daniel I A1 - Chakravarti, Aravinda A1 - Newton-Cheh, Christopher A1 - Lindgren, Cecilia M A1 - Levy, Daniel A1 - Kooner, Jaspal S A1 - Keavney, Bernard A1 - Tomaszewski, Maciej A1 - Samani, Nilesh J A1 - Howson, Joanna M M A1 - Tobin, Martin D A1 - Munroe, Patricia B A1 - Ehret, Georg B A1 - Wain, Louise V KW - Adult KW - Blood Pressure KW - Cardiovascular Diseases KW - European Continental Ancestry Group KW - Female KW - Genetic Loci KW - Genetic Predisposition to Disease KW - Genome-Wide Association Study KW - Humans KW - Hypertension KW - Male KW - Middle Aged KW - Polymorphism, Single Nucleotide KW - Risk Factors AB -

Elevated blood pressure is the leading heritable risk factor for cardiovascular disease worldwide. We report genetic association of blood pressure (systolic, diastolic, pulse pressure) among UK Biobank participants of European ancestry with independent replication in other cohorts, and robust validation of 107 independent loci. We also identify new independent variants at 11 previously reported blood pressure loci. In combination with results from a range of in silico functional analyses and wet bench experiments, our findings highlight new biological pathways for blood pressure regulation enriched for genes expressed in vascular tissues and identify potential therapeutic targets for hypertension. Results from genetic risk score models raise the possibility of a precision medicine approach through early lifestyle intervention to offset the impact of blood pressure-raising genetic variants on future cardiovascular disease risk.

VL - 49 IS - 3 U1 - http://www.ncbi.nlm.nih.gov/pubmed/28135244?dopt=Abstract ER - TY - JOUR T1 - Rare and low-frequency coding variants alter human adult height. JF - Nature Y1 - 2017 A1 - Marouli, Eirini A1 - Graff, Mariaelisa A1 - Medina-Gomez, Carolina A1 - Lo, Ken Sin A1 - Wood, Andrew R A1 - Kjaer, Troels R A1 - Fine, Rebecca S A1 - Lu, Yingchang A1 - Schurmann, Claudia A1 - Highland, Heather M A1 - Rüeger, Sina A1 - Thorleifsson, Gudmar A1 - Justice, Anne E A1 - Lamparter, David A1 - Stirrups, Kathleen E A1 - Turcot, Valérie A1 - Young, Kristin L A1 - Winkler, Thomas W A1 - Esko, Tõnu A1 - Karaderi, Tugce A1 - Locke, Adam E A1 - Masca, Nicholas G D A1 - Ng, Maggie C Y A1 - Mudgal, Poorva A1 - Rivas, Manuel A A1 - Vedantam, Sailaja A1 - Mahajan, Anubha A1 - Guo, Xiuqing A1 - Abecasis, Goncalo A1 - Aben, Katja K A1 - Adair, Linda S A1 - Alam, Dewan S A1 - Albrecht, Eva A1 - Allin, Kristine H A1 - Allison, Matthew A1 - Amouyel, Philippe A1 - Appel, Emil V A1 - Arveiler, Dominique A1 - Asselbergs, Folkert W A1 - Auer, Paul L A1 - Balkau, Beverley A1 - Banas, Bernhard A1 - Bang, Lia E A1 - Benn, Marianne A1 - Bergmann, Sven A1 - Bielak, Lawrence F A1 - Blüher, Matthias A1 - Boeing, Heiner A1 - Boerwinkle, Eric A1 - Böger, Carsten A A1 - Bonnycastle, Lori L A1 - Bork-Jensen, Jette A1 - Bots, Michiel L A1 - Bottinger, Erwin P A1 - Bowden, Donald W A1 - Brandslund, Ivan A1 - Breen, Gerome A1 - Brilliant, Murray H A1 - Broer, Linda A1 - Burt, Amber A A1 - Butterworth, Adam S A1 - Carey, David J A1 - Caulfield, Mark J A1 - Chambers, John C A1 - Chasman, Daniel I A1 - Chen, Yii-Der Ida A1 - Chowdhury, Rajiv A1 - Christensen, Cramer A1 - Chu, Audrey Y A1 - Cocca, Massimiliano A1 - Collins, Francis S A1 - Cook, James P A1 - Corley, Janie A1 - Galbany, Jordi Corominas A1 - Cox, Amanda J A1 - Cuellar-Partida, Gabriel A1 - Danesh, John A1 - Davies, Gail A1 - de Bakker, Paul I W A1 - de Borst, Gert J A1 - de Denus, Simon A1 - de Groot, Mark C H A1 - de Mutsert, Renée A1 - Deary, Ian J A1 - Dedoussis, George A1 - Demerath, Ellen W A1 - den Hollander, Anneke I A1 - Dennis, Joe G A1 - Di Angelantonio, Emanuele A1 - Drenos, Fotios A1 - Du, Mengmeng A1 - Dunning, Alison M A1 - Easton, Douglas F A1 - Ebeling, Tapani A1 - Edwards, Todd L A1 - Ellinor, Patrick T A1 - Elliott, Paul A1 - Evangelou, Evangelos A1 - Farmaki, Aliki-Eleni A1 - Faul, Jessica D A1 - Feitosa, Mary F A1 - Feng, Shuang A1 - Ferrannini, Ele A1 - Ferrario, Marco M A1 - Ferrières, Jean A1 - Florez, Jose C A1 - Ford, Ian A1 - Fornage, Myriam A1 - Franks, Paul W A1 - Frikke-Schmidt, Ruth A1 - Galesloot, Tessel E A1 - Gan, Wei A1 - Gandin, Ilaria A1 - Gasparini, Paolo A1 - Giedraitis, Vilmantas A1 - Giri, Ayush A1 - Girotto, Giorgia A1 - Gordon, Scott D A1 - Gordon-Larsen, Penny A1 - Gorski, Mathias A1 - Grarup, Niels A1 - Grove, Megan L A1 - Gudnason, Vilmundur A1 - Gustafsson, Stefan A1 - Hansen, Torben A1 - Harris, Kathleen Mullan A1 - Harris, Tamara B A1 - Hattersley, Andrew T A1 - Hayward, Caroline A1 - He, Liang A1 - Heid, Iris M A1 - Heikkilä, Kauko A1 - Helgeland, Øyvind A1 - Hernesniemi, Jussi A1 - Hewitt, Alex W A1 - Hocking, Lynne J A1 - Hollensted, Mette A1 - Holmen, Oddgeir L A1 - Hovingh, G Kees A1 - Howson, Joanna M M A1 - Hoyng, Carel B A1 - Huang, Paul L A1 - Hveem, Kristian A1 - Ikram, M Arfan A1 - Ingelsson, Erik A1 - Jackson, Anne U A1 - Jansson, Jan-Håkan A1 - Jarvik, Gail P A1 - Jensen, Gorm B A1 - Jhun, Min A A1 - Jia, Yucheng A1 - Jiang, Xuejuan A1 - Johansson, Stefan A1 - Jørgensen, Marit E A1 - Jørgensen, Torben A1 - Jousilahti, Pekka A1 - Jukema, J Wouter A1 - Kahali, Bratati A1 - Kahn, René S A1 - Kähönen, Mika A1 - Kamstrup, Pia R A1 - Kanoni, Stavroula A1 - Kaprio, Jaakko A1 - Karaleftheri, Maria A1 - Kardia, Sharon L R A1 - Karpe, Fredrik A1 - Kee, Frank A1 - Keeman, Renske A1 - Kiemeney, Lambertus A A1 - Kitajima, Hidetoshi A1 - Kluivers, Kirsten B A1 - Kocher, Thomas A1 - Komulainen, Pirjo A1 - Kontto, Jukka A1 - Kooner, Jaspal S A1 - Kooperberg, Charles A1 - Kovacs, Peter A1 - Kriebel, Jennifer A1 - Kuivaniemi, Helena A1 - Küry, Sébastien A1 - Kuusisto, Johanna A1 - La Bianca, Martina A1 - Laakso, Markku A1 - Lakka, Timo A A1 - Lange, Ethan M A1 - Lange, Leslie A A1 - Langefeld, Carl D A1 - Langenberg, Claudia A1 - Larson, Eric B A1 - Lee, I-Te A1 - Lehtimäki, Terho A1 - Lewis, Cora E A1 - Li, Huaixing A1 - Li, Jin A1 - Li-Gao, Ruifang A1 - Lin, Honghuang A1 - Lin, Li-An A1 - Lin, Xu A1 - Lind, Lars A1 - Lindström, Jaana A1 - Linneberg, Allan A1 - Liu, Yeheng A1 - Liu, Yongmei A1 - Lophatananon, Artitaya A1 - Luan, Jian'an A1 - Lubitz, Steven A A1 - Lyytikäinen, Leo-Pekka A1 - Mackey, David A A1 - Madden, Pamela A F A1 - Manning, Alisa K A1 - Männistö, Satu A1 - Marenne, Gaëlle A1 - Marten, Jonathan A1 - Martin, Nicholas G A1 - Mazul, Angela L A1 - Meidtner, Karina A1 - Metspalu, Andres A1 - Mitchell, Paul A1 - Mohlke, Karen L A1 - Mook-Kanamori, Dennis O A1 - Morgan, Anna A1 - Morris, Andrew D A1 - Morris, Andrew P A1 - Müller-Nurasyid, Martina A1 - Munroe, Patricia B A1 - Nalls, Mike A A1 - Nauck, Matthias A1 - Nelson, Christopher P A1 - Neville, Matt A1 - Nielsen, Sune F A1 - Nikus, Kjell A1 - Njølstad, Pål R A1 - Nordestgaard, Børge G A1 - Ntalla, Ioanna A1 - O'Connel, Jeffrey R A1 - Oksa, Heikki A1 - Loohuis, Loes M Olde A1 - Ophoff, Roel A A1 - Owen, Katharine R A1 - Packard, Chris J A1 - Padmanabhan, Sandosh A1 - Palmer, Colin N A A1 - Pasterkamp, Gerard A1 - Patel, Aniruddh P A1 - Pattie, Alison A1 - Pedersen, Oluf A1 - Peissig, Peggy L A1 - Peloso, Gina M A1 - Pennell, Craig E A1 - Perola, Markus A1 - Perry, James A A1 - Perry, John R B A1 - Person, Thomas N A1 - Pirie, Ailith A1 - Polasek, Ozren A1 - Posthuma, Danielle A1 - Raitakari, Olli T A1 - Rasheed, Asif A1 - Rauramaa, Rainer A1 - Reilly, Dermot F A1 - Reiner, Alex P A1 - Renstrom, Frida A1 - Ridker, Paul M A1 - Rioux, John D A1 - Robertson, Neil A1 - Robino, Antonietta A1 - Rolandsson, Olov A1 - Rudan, Igor A1 - Ruth, Katherine S A1 - Saleheen, Danish A1 - Salomaa, Veikko A1 - Samani, Nilesh J A1 - Sandow, Kevin A1 - Sapkota, Yadav A1 - Sattar, Naveed A1 - Schmidt, Marjanka K A1 - Schreiner, Pamela J A1 - Schulze, Matthias B A1 - Scott, Robert A A1 - Segura-Lepe, Marcelo P A1 - Shah, Svati A1 - Sim, Xueling A1 - Sivapalaratnam, Suthesh A1 - Small, Kerrin S A1 - Smith, Albert Vernon A1 - Smith, Jennifer A A1 - Southam, Lorraine A1 - Spector, Timothy D A1 - Speliotes, Elizabeth K A1 - Starr, John M A1 - Steinthorsdottir, Valgerdur A1 - Stringham, Heather M A1 - Stumvoll, Michael A1 - Surendran, Praveen A1 - 't Hart, Leen M A1 - Tansey, Katherine E A1 - Tardif, Jean-Claude A1 - Taylor, Kent D A1 - Teumer, Alexander A1 - Thompson, Deborah J A1 - Thorsteinsdottir, Unnur A1 - Thuesen, Betina H A1 - Tönjes, Anke A1 - Tromp, Gerard A1 - Trompet, Stella A1 - Tsafantakis, Emmanouil A1 - Tuomilehto, Jaakko A1 - Tybjaerg-Hansen, Anne A1 - Tyrer, Jonathan P A1 - Uher, Rudolf A1 - Uitterlinden, André G A1 - Ulivi, Sheila A1 - van der Laan, Sander W A1 - Van Der Leij, Andries R A1 - van Duijn, Cornelia M A1 - van Schoor, Natasja M A1 - van Setten, Jessica A1 - Varbo, Anette A1 - Varga, Tibor V A1 - Varma, Rohit A1 - Edwards, Digna R Velez A1 - Vermeulen, Sita H A1 - Vestergaard, Henrik A1 - Vitart, Veronique A1 - Vogt, Thomas F A1 - Vozzi, Diego A1 - Walker, Mark A1 - Wang, Feijie A1 - Wang, Carol A A1 - Wang, Shuai A1 - Wang, Yiqin A1 - Wareham, Nicholas J A1 - Warren, Helen R A1 - Wessel, Jennifer A1 - Willems, Sara M A1 - Wilson, James G A1 - Witte, Daniel R A1 - Woods, Michael O A1 - Wu, Ying A1 - Yaghootkar, Hanieh A1 - Yao, Jie A1 - Yao, Pang A1 - Yerges-Armstrong, Laura M A1 - Young, Robin A1 - Zeggini, Eleftheria A1 - Zhan, Xiaowei A1 - Zhang, Weihua A1 - Zhao, Jing Hua A1 - Zhao, Wei A1 - Zhao, Wei A1 - Zheng, He A1 - Zhou, Wei A1 - Rotter, Jerome I A1 - Boehnke, Michael A1 - Kathiresan, Sekar A1 - McCarthy, Mark I A1 - Willer, Cristen J A1 - Stefansson, Kari A1 - Borecki, Ingrid B A1 - Liu, Dajiang J A1 - North, Kari E A1 - Heard-Costa, Nancy L A1 - Pers, Tune H A1 - Lindgren, Cecilia M A1 - Oxvig, Claus A1 - Kutalik, Zoltán A1 - Rivadeneira, Fernando A1 - Loos, Ruth J F A1 - Frayling, Timothy M A1 - Hirschhorn, Joel N A1 - Deloukas, Panos A1 - Lettre, Guillaume KW - ADAMTS Proteins KW - Adult KW - Alleles KW - Body Height KW - Cell Adhesion Molecules KW - Female KW - Gene Frequency KW - Genetic Variation KW - Genome, Human KW - Glycoproteins KW - Glycosaminoglycans KW - Hedgehog Proteins KW - Humans KW - Intercellular Signaling Peptides and Proteins KW - Interferon Regulatory Factors KW - Interleukin-11 Receptor alpha Subunit KW - Male KW - Multifactorial Inheritance KW - NADPH Oxidase 4 KW - NADPH Oxidases KW - Phenotype KW - Pregnancy-Associated Plasma Protein-A KW - Procollagen N-Endopeptidase KW - Proteoglycans KW - Proteolysis KW - Receptors, Androgen KW - Somatomedins AB -

Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height-increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.

VL - 542 IS - 7640 U1 - http://www.ncbi.nlm.nih.gov/pubmed/28146470?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 - 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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 - 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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 - Global, regional, and national levels of neonatal, infant, and under-5 mortality during 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. JF - Lancet Y1 - 2014 A1 - Wang, Haidong A1 - Liddell, Chelsea A A1 - Coates, Matthew M A1 - Mooney, Meghan D A1 - Levitz, Carly E A1 - Schumacher, Austin E A1 - Apfel, Henry A1 - Iannarone, Marissa A1 - Phillips, Bryan A1 - Lofgren, Katherine T A1 - Sandar, Logan A1 - Dorrington, Rob E A1 - Rakovac, Ivo A1 - Jacobs, Troy A A1 - Liang, Xiaofeng A1 - Zhou, Maigeng A1 - Zhu, Jun A1 - Yang, Gonghuan A1 - Wang, Yanping A1 - Liu, Shiwei A1 - Li, Yichong A1 - Ozgoren, Ayse Abbasoglu A1 - Abera, Semaw Ferede A1 - Abubakar, Ibrahim A1 - Achoki, Tom A1 - Adelekan, Ademola A1 - Ademi, Zanfina A1 - Alemu, Zewdie Aderaw A1 - Allen, Peter J A1 - AlMazroa, Mohammad AbdulAziz A1 - Alvarez, Elena A1 - Amankwaa, Adansi A A1 - Amare, Azmeraw T A1 - Ammar, Walid A1 - Anwari, Palwasha A1 - Cunningham, Solveig Argeseanu A1 - Asad, Majed Masoud A1 - Assadi, Reza A1 - Banerjee, Amitava A1 - Basu, Sanjay A1 - Bedi, Neeraj A1 - Bekele, Tolesa A1 - Bell, Michelle L A1 - Bhutta, Zulfiqar A1 - Blore, Jed D A1 - Basara, Berrak Bora A1 - Boufous, Soufiane A1 - Breitborde, Nicholas A1 - Bruce, Nigel G A1 - Bui, Linh Ngoc A1 - Carapetis, Jonathan R A1 - Cárdenas, Rosario A1 - Carpenter, David O A1 - Caso, Valeria A1 - Castro, Ruben Estanislao A1 - Catalá-López, Ferrán A1 - Cavlin, Alanur A1 - Che, Xuan A1 - Chiang, Peggy Pei-Chia A1 - Chowdhury, Rajiv A1 - Christophi, Costas A A1 - Chuang, Ting-Wu A1 - Cirillo, Massimo A1 - da Costa Leite, Iuri A1 - Courville, Karen J A1 - Dandona, Lalit A1 - Dandona, Rakhi A1 - Davis, Adrian A1 - Dayama, Anand A1 - Deribe, Kebede A1 - Dharmaratne, Samath D A1 - Dherani, Mukesh K A1 - Dilmen, Uğur A1 - Ding, Eric L A1 - Edmond, Karen M A1 - Ermakov, Sergei Petrovich A1 - Farzadfar, Farshad A1 - Fereshtehnejad, Seyed-Mohammad A1 - Fijabi, Daniel Obadare A1 - Foigt, Nataliya A1 - Forouzanfar, Mohammad H A1 - Garcia, Ana C A1 - Geleijnse, Johanna M A1 - Gessner, Bradford D A1 - Goginashvili, Ketevan A1 - Gona, Philimon A1 - Goto, Atsushi A1 - Gouda, Hebe N A1 - Green, Mark A A1 - Greenwell, Karen Fern A1 - Gugnani, Harish Chander A1 - Gupta, Rahul A1 - Hamadeh, Randah Ribhi A1 - Hammami, Mouhanad A1 - Harb, Hilda L A1 - Hay, Simon A1 - Hedayati, Mohammad T A1 - Hosgood, H Dean A1 - Hoy, Damian G A1 - Idrisov, Bulat T A1 - Islami, Farhad A1 - Ismayilova, Samaya A1 - Jha, Vivekanand A1 - Jiang, Guohong A1 - Jonas, Jost B A1 - Juel, Knud A1 - Kabagambe, Edmond Kato A1 - Kazi, Dhruv S A1 - Kengne, Andre Pascal A1 - Kereselidze, Maia A1 - Khader, Yousef Saleh A1 - Khalifa, Shams Eldin Ali Hassan A1 - Khang, Young-Ho A1 - Kim, Daniel A1 - Kinfu, Yohannes A1 - Kinge, Jonas M A1 - Kokubo, Yoshihiro A1 - Kosen, Soewarta A1 - Defo, Barthelemy Kuate A1 - Kumar, G Anil A1 - Kumar, Kaushalendra A1 - Kumar, Ravi B A1 - Lai, Taavi A1 - Lan, Qing A1 - Larsson, Anders A1 - Lee, Jong-Tae A1 - Leinsalu, Mall A1 - Lim, Stephen S A1 - Lipshultz, Steven E A1 - Logroscino, Giancarlo A1 - Lotufo, Paulo A A1 - Lunevicius, Raimundas A1 - Lyons, Ronan Anthony A1 - Ma, Stefan A1 - Mahdi, Abbas Ali A1 - Marzan, Melvin Barrientos A1 - Mashal, Mohammad Taufiq A1 - Mazorodze, Tasara T A1 - McGrath, John J A1 - Memish, Ziad A A1 - Mendoza, Walter A1 - Mensah, George A A1 - Meretoja, Atte A1 - Miller, Ted R A1 - Mills, Edward J A1 - Mohammad, Karzan Abdulmuhsin A1 - Mokdad, Ali H A1 - Monasta, Lorenzo A1 - Montico, Marcella A1 - Moore, Ami R A1 - Moschandreas, Joanna A1 - Msemburi, William T A1 - Mueller, Ulrich O A1 - Muszynska, Magdalena M A1 - Naghavi, Mohsen A1 - Naidoo, Kovin S A1 - Narayan, K M Venkat A1 - Nejjari, Chakib A1 - Ng, Marie A1 - de Dieu Ngirabega, Jean A1 - Nieuwenhuijsen, Mark J A1 - Nyakarahuka, Luke A1 - Ohkubo, Takayoshi A1 - Omer, Saad B A1 - Caicedo, Angel J Paternina A1 - Pillay-van Wyk, Victoria A1 - Pope, Dan A1 - Pourmalek, Farshad A1 - Prabhakaran, Dorairaj A1 - Rahman, Sajjad U R A1 - Rana, Saleem M A1 - Reilly, Robert Quentin A1 - Rojas-Rueda, David A1 - Ronfani, Luca A1 - Rushton, Lesley A1 - Saeedi, Mohammad Yahya A1 - Salomon, Joshua A A1 - Sampson, Uchechukwu A1 - Santos, Itamar S A1 - Sawhney, Monika A1 - Schmidt, Jürgen C A1 - Shakh-Nazarova, Marina A1 - She, Jun A1 - Sheikhbahaei, Sara A1 - Shibuya, Kenji A1 - Shin, Hwashin Hyun A1 - Shishani, Kawkab A1 - Shiue, Ivy A1 - Sigfusdottir, Inga Dora A1 - Singh, Jasvinder A A1 - Skirbekk, Vegard A1 - Sliwa, Karen A1 - Soshnikov, Sergey S A1 - Sposato, Luciano A A1 - Stathopoulou, Vasiliki Kalliopi A1 - Stroumpoulis, Konstantinos A1 - Tabb, Karen M A1 - Talongwa, Roberto Tchio A1 - Teixeira, Carolina Maria A1 - Terkawi, Abdullah Sulieman A1 - Thomson, Alan J A1 - Thorne-Lyman, Andrew L A1 - Toyoshima, Hideaki A1 - Dimbuene, Zacharie Tsala A1 - Uwaliraye, Parfait A1 - Uzun, Selen Begüm A1 - Vasankari, Tommi J A1 - Vasconcelos, Ana Maria Nogales A1 - Vlassov, Vasiliy Victorovich A1 - Vollset, Stein Emil A1 - Waller, Stephen A1 - Wan, Xia A1 - Weichenthal, Scott A1 - Weiderpass, Elisabete A1 - Weintraub, Robert G A1 - Westerman, Ronny A1 - Wilkinson, James D A1 - Williams, Hywel C A1 - Yang, Yang C A1 - Yentur, Gokalp Kadri A1 - Yip, Paul A1 - Yonemoto, Naohiro A1 - Younis, Mustafa A1 - Yu, Chuanhua A1 - Jin, Kim Yun A1 - El Sayed Zaki, Maysaa A1 - Zhu, Shankuan A1 - Vos, Theo A1 - Lopez, Alan D A1 - Murray, Christopher J L KW - Child Mortality KW - Child, Preschool KW - Global Health KW - Humans KW - Infant KW - Infant Mortality KW - Infant, Newborn KW - Organizational Objectives KW - Risk Factors KW - Socioeconomic Factors AB -

BACKGROUND: Remarkable financial and political efforts have been focused on the reduction of child mortality during the past few decades. Timely measurements of levels and trends in under-5 mortality are important to assess progress towards the Millennium Development Goal 4 (MDG 4) target of reduction of child mortality by two thirds from 1990 to 2015, and to identify models of success.

METHODS: We generated updated estimates of child mortality in early neonatal (age 0-6 days), late neonatal (7-28 days), postneonatal (29-364 days), childhood (1-4 years), and under-5 (0-4 years) age groups for 188 countries from 1970 to 2013, with more than 29,000 survey, census, vital registration, and sample registration datapoints. We used Gaussian process regression with adjustments for bias and non-sampling error to synthesise the data for under-5 mortality for each country, and a separate model to estimate mortality for more detailed age groups. We used explanatory mixed effects regression models to assess the association between under-5 mortality and income per person, maternal education, HIV child death rates, secular shifts, and other factors. To quantify the contribution of these different factors and birth numbers to the change in numbers of deaths in under-5 age groups from 1990 to 2013, we used Shapley decomposition. We used estimated rates of change between 2000 and 2013 to construct under-5 mortality rate scenarios out to 2030.

FINDINGS: We estimated that 6·3 million (95% UI 6·0-6·6) children under-5 died in 2013, a 64% reduction from 17·6 million (17·1-18·1) in 1970. In 2013, child mortality rates ranged from 152·5 per 1000 livebirths (130·6-177·4) in Guinea-Bissau to 2·3 (1·8-2·9) per 1000 in Singapore. The annualised rates of change from 1990 to 2013 ranged from -6·8% to 0·1%. 99 of 188 countries, including 43 of 48 countries in sub-Saharan Africa, had faster decreases in child mortality during 2000-13 than during 1990-2000. In 2013, neonatal deaths accounted for 41·6% of under-5 deaths compared with 37·4% in 1990. Compared with 1990, in 2013, rising numbers of births, especially in sub-Saharan Africa, led to 1·4 million more child deaths, and rising income per person and maternal education led to 0·9 million and 2·2 million fewer deaths, respectively. Changes in secular trends led to 4·2 million fewer deaths. Unexplained factors accounted for only -1% of the change in child deaths. In 30 developing countries, decreases since 2000 have been faster than predicted attributable to income, education, and secular shift alone.

INTERPRETATION: Only 27 developing countries are expected to achieve MDG 4. Decreases since 2000 in under-5 mortality rates are accelerating in many developing countries, especially in sub-Saharan Africa. The Millennium Declaration and increased development assistance for health might have been a factor in faster decreases in some developing countries. Without further accelerated progress, many countries in west and central Africa will still have high levels of under-5 mortality in 2030.

FUNDING: Bill & Melinda Gates Foundation, US Agency for International Development.

VL - 384 IS - 9947 U1 - http://www.ncbi.nlm.nih.gov/pubmed/24797572?dopt=Abstract ER -