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

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.

%B Nat Genet %V 49 %P 403-415 %8 2017 Mar %G eng %N 3 %1 http://www.ncbi.nlm.nih.gov/pubmed/28135244?dopt=Abstract %R 10.1038/ng.3768 %0 Journal Article %J Nature %D 2017 %T Rare and low-frequency coding variants alter human adult height. %A Marouli, Eirini %A Graff, Mariaelisa %A Medina-Gomez, Carolina %A Lo, Ken Sin %A Wood, Andrew R %A Kjaer, Troels R %A Fine, Rebecca S %A Lu, Yingchang %A Schurmann, Claudia %A Highland, Heather M %A Rüeger, Sina %A Thorleifsson, Gudmar %A Justice, Anne E %A Lamparter, David %A Stirrups, Kathleen E %A Turcot, Valérie %A Young, Kristin L %A Winkler, Thomas W %A Esko, Tõnu %A Karaderi, Tugce %A Locke, Adam E %A Masca, Nicholas G D %A Ng, Maggie C Y %A Mudgal, Poorva %A Rivas, Manuel A %A Vedantam, Sailaja %A Mahajan, Anubha %A Guo, Xiuqing %A Abecasis, Goncalo %A Aben, Katja K %A Adair, Linda S %A Alam, Dewan S %A Albrecht, Eva %A Allin, Kristine H %A Allison, Matthew %A Amouyel, Philippe %A Appel, Emil V %A Arveiler, Dominique %A Asselbergs, Folkert W %A Auer, Paul L %A Balkau, Beverley %A Banas, Bernhard %A Bang, Lia E %A Benn, Marianne %A Bergmann, Sven %A Bielak, Lawrence F %A Blüher, Matthias %A Boeing, Heiner %A Boerwinkle, Eric %A Böger, Carsten A %A Bonnycastle, Lori L %A Bork-Jensen, Jette %A Bots, Michiel L %A Bottinger, Erwin P %A Bowden, Donald W %A Brandslund, Ivan %A Breen, Gerome %A Brilliant, Murray H %A Broer, Linda %A Burt, Amber A %A Butterworth, Adam S %A Carey, David J %A Caulfield, Mark J %A Chambers, John C %A Chasman, Daniel I %A Chen, Yii-Der Ida %A Chowdhury, Rajiv %A Christensen, Cramer %A Chu, Audrey Y %A Cocca, Massimiliano %A Collins, Francis S %A Cook, James P %A Corley, Janie %A Galbany, Jordi Corominas %A Cox, Amanda J %A Cuellar-Partida, Gabriel %A Danesh, John %A Davies, Gail %A de Bakker, Paul I W %A de Borst, Gert J %A de Denus, Simon %A de Groot, Mark C H %A de Mutsert, Renée %A Deary, Ian J %A Dedoussis, George %A Demerath, Ellen W %A den Hollander, Anneke I %A Dennis, Joe G %A Di Angelantonio, Emanuele %A Drenos, Fotios %A Du, Mengmeng %A Dunning, Alison M %A Easton, Douglas F %A Ebeling, Tapani %A Edwards, Todd L %A Ellinor, Patrick T %A Elliott, Paul %A Evangelou, Evangelos %A Farmaki, Aliki-Eleni %A Faul, Jessica D %A Feitosa, Mary F %A Feng, Shuang %A Ferrannini, Ele %A Ferrario, Marco M %A Ferrières, Jean %A Florez, Jose C %A Ford, Ian %A Fornage, Myriam %A Franks, Paul W %A Frikke-Schmidt, Ruth %A Galesloot, Tessel E %A Gan, Wei %A Gandin, Ilaria %A Gasparini, Paolo %A Giedraitis, Vilmantas %A Giri, Ayush %A Girotto, Giorgia %A Gordon, Scott D %A Gordon-Larsen, Penny %A Gorski, Mathias %A Grarup, Niels %A Grove, Megan L %A Gudnason, Vilmundur %A Gustafsson, Stefan %A Hansen, Torben %A Harris, Kathleen Mullan %A Harris, Tamara B %A Hattersley, Andrew T %A Hayward, Caroline %A He, Liang %A Heid, Iris M %A Heikkilä, Kauko %A Helgeland, Øyvind %A Hernesniemi, Jussi %A Hewitt, Alex W %A Hocking, Lynne J %A Hollensted, Mette %A Holmen, Oddgeir L %A Hovingh, G Kees %A Howson, Joanna M M %A Hoyng, Carel B %A Huang, Paul L %A Hveem, Kristian %A Ikram, M Arfan %A Ingelsson, Erik %A Jackson, Anne U %A Jansson, Jan-Håkan %A Jarvik, Gail P %A Jensen, Gorm B %A Jhun, Min A %A Jia, Yucheng %A Jiang, Xuejuan %A Johansson, Stefan %A Jørgensen, Marit E %A Jørgensen, Torben %A Jousilahti, Pekka %A Jukema, J Wouter %A Kahali, Bratati %A Kahn, René S %A Kähönen, Mika %A Kamstrup, Pia R %A Kanoni, Stavroula %A Kaprio, Jaakko %A Karaleftheri, Maria %A Kardia, Sharon L R %A Karpe, Fredrik %A Kee, Frank %A Keeman, Renske %A Kiemeney, Lambertus A %A Kitajima, Hidetoshi %A Kluivers, Kirsten B %A Kocher, Thomas %A Komulainen, Pirjo %A Kontto, Jukka %A Kooner, Jaspal S %A Kooperberg, Charles %A Kovacs, Peter %A Kriebel, Jennifer %A Kuivaniemi, Helena %A Küry, Sébastien %A Kuusisto, Johanna %A La Bianca, Martina %A Laakso, Markku %A Lakka, Timo A %A Lange, Ethan M %A Lange, Leslie A %A Langefeld, Carl D %A Langenberg, Claudia %A Larson, Eric B %A Lee, I-Te %A Lehtimäki, Terho %A Lewis, Cora E %A Li, Huaixing %A Li, Jin %A Li-Gao, Ruifang %A Lin, Honghuang %A Lin, Li-An %A Lin, Xu %A Lind, Lars %A Lindström, Jaana %A Linneberg, Allan %A Liu, Yeheng %A Liu, Yongmei %A Lophatananon, Artitaya %A Luan, Jian'an %A Lubitz, Steven A %A Lyytikäinen, Leo-Pekka %A Mackey, David A %A Madden, Pamela A F %A Manning, Alisa K %A Männistö, Satu %A Marenne, Gaëlle %A Marten, Jonathan %A Martin, Nicholas G %A Mazul, Angela L %A Meidtner, Karina %A Metspalu, Andres %A Mitchell, Paul %A Mohlke, Karen L %A Mook-Kanamori, Dennis O %A Morgan, Anna %A Morris, Andrew D %A Morris, Andrew P %A Müller-Nurasyid, Martina %A Munroe, Patricia B %A Nalls, Mike A %A Nauck, Matthias %A Nelson, Christopher P %A Neville, Matt %A Nielsen, Sune F %A Nikus, Kjell %A Njølstad, Pål R %A Nordestgaard, Børge G %A Ntalla, Ioanna %A O'Connel, Jeffrey R %A Oksa, Heikki %A Loohuis, Loes M Olde %A Ophoff, Roel A %A Owen, Katharine R %A Packard, Chris J %A Padmanabhan, Sandosh %A Palmer, Colin N A %A Pasterkamp, Gerard %A Patel, Aniruddh P %A Pattie, Alison %A Pedersen, Oluf %A Peissig, Peggy L %A Peloso, Gina M %A Pennell, Craig E %A Perola, Markus %A Perry, James A %A Perry, John R B %A Person, Thomas N %A Pirie, Ailith %A Polasek, Ozren %A Posthuma, Danielle %A Raitakari, Olli T %A Rasheed, Asif %A Rauramaa, Rainer %A Reilly, Dermot F %A Reiner, Alex P %A Renstrom, Frida %A Ridker, Paul M %A Rioux, John D %A Robertson, Neil %A Robino, Antonietta %A Rolandsson, Olov %A Rudan, Igor %A Ruth, Katherine S %A Saleheen, Danish %A Salomaa, Veikko %A Samani, Nilesh J %A Sandow, Kevin %A Sapkota, Yadav %A Sattar, Naveed %A Schmidt, Marjanka K %A Schreiner, Pamela J %A Schulze, Matthias B %A Scott, Robert A %A Segura-Lepe, Marcelo P %A Shah, Svati %A Sim, Xueling %A Sivapalaratnam, Suthesh %A Small, Kerrin S %A Smith, Albert Vernon %A Smith, Jennifer A %A Southam, Lorraine %A Spector, Timothy D %A Speliotes, Elizabeth K %A Starr, John M %A Steinthorsdottir, Valgerdur %A Stringham, Heather M %A Stumvoll, Michael %A Surendran, Praveen %A 't Hart, Leen M %A Tansey, Katherine E %A Tardif, Jean-Claude %A Taylor, Kent D %A Teumer, Alexander %A Thompson, Deborah J %A Thorsteinsdottir, Unnur %A Thuesen, Betina H %A Tönjes, Anke %A Tromp, Gerard %A Trompet, Stella %A Tsafantakis, Emmanouil %A Tuomilehto, Jaakko %A Tybjaerg-Hansen, Anne %A Tyrer, Jonathan P %A Uher, Rudolf %A Uitterlinden, André G %A Ulivi, Sheila %A van der Laan, Sander W %A Van Der Leij, Andries R %A van Duijn, Cornelia M %A van Schoor, Natasja M %A van Setten, Jessica %A Varbo, Anette %A Varga, Tibor V %A Varma, Rohit %A Edwards, Digna R Velez %A Vermeulen, Sita H %A Vestergaard, Henrik %A Vitart, Veronique %A Vogt, Thomas F %A Vozzi, Diego %A Walker, Mark %A Wang, Feijie %A Wang, Carol A %A Wang, Shuai %A Wang, Yiqin %A Wareham, Nicholas J %A Warren, Helen R %A Wessel, Jennifer %A Willems, Sara M %A Wilson, James G %A Witte, Daniel R %A Woods, Michael O %A Wu, Ying %A Yaghootkar, Hanieh %A Yao, Jie %A Yao, Pang %A Yerges-Armstrong, Laura M %A Young, Robin %A Zeggini, Eleftheria %A Zhan, Xiaowei %A Zhang, Weihua %A Zhao, Jing Hua %A Zhao, Wei %A Zhao, Wei %A Zheng, He %A Zhou, Wei %A Rotter, Jerome I %A Boehnke, Michael %A Kathiresan, Sekar %A McCarthy, Mark I %A Willer, Cristen J %A Stefansson, Kari %A Borecki, Ingrid B %A Liu, Dajiang J %A North, Kari E %A Heard-Costa, Nancy L %A Pers, Tune H %A Lindgren, Cecilia M %A Oxvig, Claus %A Kutalik, Zoltán %A Rivadeneira, Fernando %A Loos, Ruth J F %A Frayling, Timothy M %A Hirschhorn, Joel N %A Deloukas, Panos %A Lettre, Guillaume %K ADAMTS Proteins %K Adult %K Alleles %K Body Height %K Cell Adhesion Molecules %K Female %K Gene Frequency %K Genetic Variation %K Genome, Human %K Glycoproteins %K Glycosaminoglycans %K Hedgehog Proteins %K Humans %K Intercellular Signaling Peptides and Proteins %K Interferon Regulatory Factors %K Interleukin-11 Receptor alpha Subunit %K Male %K Multifactorial Inheritance %K NADPH Oxidase 4 %K NADPH Oxidases %K Phenotype %K Pregnancy-Associated Plasma Protein-A %K Procollagen N-Endopeptidase %K Proteoglycans %K Proteolysis %K Receptors, Androgen %K Somatomedins %X

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.

%B Nature %V 542 %P 186-190 %8 2017 02 09 %G eng %N 7640 %1 http://www.ncbi.nlm.nih.gov/pubmed/28146470?dopt=Abstract %R 10.1038/nature21039 %0 Journal Article %J Lancet %D 2015 %T 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. %A Forouzanfar, Mohammad H %A Alexander, Lily %A Anderson, H Ross %A Bachman, Victoria F %A Biryukov, Stan %A Brauer, Michael %A Burnett, Richard %A Casey, Daniel %A Coates, Matthew M %A Cohen, Aaron %A Delwiche, Kristen %A Estep, Kara %A Frostad, Joseph J %A Astha, K C %A Kyu, Hmwe H %A Moradi-Lakeh, Maziar %A Ng, Marie %A Slepak, Erica Leigh %A Thomas, Bernadette A %A Wagner, Joseph %A Aasvang, Gunn Marit %A Abbafati, Cristiana %A Abbasoglu Ozgoren, Ayse %A Abd-Allah, Foad %A Abera, Semaw F %A Aboyans, Victor %A Abraham, Biju %A Abraham, Jerry Puthenpurakal %A Abubakar, Ibrahim %A Abu-Rmeileh, Niveen M E %A Aburto, Tania C %A Achoki, Tom %A Adelekan, Ademola %A Adofo, Koranteng %A Adou, Arsène K %A Adsuar, José C %A Afshin, Ashkan %A Agardh, Emilie E %A Al Khabouri, Mazin J %A Al Lami, Faris H %A Alam, Sayed Saidul %A Alasfoor, Deena %A Albittar, Mohammed I %A Alegretti, Miguel A %A Aleman, Alicia V %A Alemu, Zewdie A %A Alfonso-Cristancho, Rafael %A Alhabib, Samia %A Ali, Raghib %A Ali, Mohammed K %A Alla, François %A Allebeck, Peter %A Allen, Peter J %A Alsharif, Ubai %A Alvarez, Elena %A Alvis-Guzmán, Nelson %A Amankwaa, Adansi A %A Amare, Azmeraw T %A Ameh, Emmanuel A %A Ameli, Omid %A Amini, Heresh %A Ammar, Walid %A Anderson, Benjamin O %A Antonio, Carl Abelardo T %A Anwari, Palwasha %A Argeseanu Cunningham, Solveig %A Arnlöv, Johan %A Arsenijevic, Valentina S Arsic %A Artaman, Al %A Asghar, Rana J %A Assadi, Reza %A Atkins, Lydia S %A Atkinson, Charles %A Avila, Marco A %A Awuah, Baffour %A Badawi, Alaa %A Bahit, Maria C %A Bakfalouni, Talal %A Balakrishnan, Kalpana %A Balalla, Shivanthi %A Balu, Ravi Kumar %A Banerjee, Amitava %A Barber, Ryan M %A Barker-Collo, Suzanne L %A Barquera, Simon %A Barregard, Lars %A Barrero, Lope H %A Barrientos-Gutierrez, Tonatiuh %A Basto-Abreu, Ana C %A Basu, Arindam %A Basu, Sanjay %A Basulaiman, Mohammed O %A Batis Ruvalcaba, Carolina %A Beardsley, Justin %A Bedi, Neeraj %A Bekele, Tolesa %A Bell, Michelle L %A Benjet, Corina %A Bennett, Derrick A %A Benzian, Habib %A Bernabe, Eduardo %A Beyene, Tariku J %A Bhala, Neeraj %A Bhalla, Ashish %A Bhutta, Zulfiqar A %A Bikbov, Boris %A Bin Abdulhak, Aref A %A Blore, Jed D %A Blyth, Fiona M %A Bohensky, Megan A %A Bora Başara, Berrak %A Borges, Guilherme %A Bornstein, Natan M %A Bose, Dipan %A Boufous, Soufiane %A Bourne, Rupert R %A Brainin, Michael %A Brazinova, Alexandra %A Breitborde, Nicholas J %A Brenner, Hermann %A Briggs, Adam D M %A Broday, David M %A Brooks, Peter M %A Bruce, Nigel G %A Brugha, Traolach S %A 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%A Heredia-Pi, Ileana B %A Hernandez, Lucia %A Heuton, Kyle R %A Heydarpour, Pouria %A Hijar, Martha %A Hoek, Hans W %A Hoffman, Howard J %A Hornberger, John C %A Hosgood, H Dean %A Hoy, Damian G %A Hsairi, Mohamed %A Hu, Guoqing %A Hu, Howard %A Huang, Cheng %A Huang, John J %A Hubbell, Bryan J %A Huiart, Laetitia %A Husseini, Abdullatif %A Iannarone, Marissa L %A Iburg, Kim M %A Idrisov, Bulat T %A Ikeda, Nayu %A Innos, Kaire %A Inoue, Manami %A Islami, Farhad %A Ismayilova, Samaya %A Jacobsen, Kathryn H %A Jansen, Henrica A %A Jarvis, Deborah L %A Jassal, Simerjot K %A Jauregui, Alejandra %A Jayaraman, Sudha %A Jeemon, Panniyammakal %A Jensen, Paul N %A Jha, Vivekanand %A Jiang, Fan %A Jiang, Guohong %A Jiang, Ying %A Jonas, Jost B %A Juel, Knud %A Kan, Haidong %A Kany Roseline, Sidibe S %A Karam, Nadim E %A Karch, André %A Karema, Corine K %A Karthikeyan, Ganesan %A Kaul, Anil %A Kawakami, Norito %A Kazi, Dhruv S %A Kemp, Andrew H %A Kengne, Andre P %A Keren, Andre %A Khader, Yousef S %A Khalifa, Shams Eldin Ali Hassan %A Khan, Ejaz A %A Khang, Young-Ho %A Khatibzadeh, Shahab %A Khonelidze, Irma %A Kieling, Christian %A Kim, Daniel %A Kim, Sungroul %A Kim, Yunjin %A Kimokoti, Ruth W %A Kinfu, Yohannes %A Kinge, Jonas M %A Kissela, Brett M %A Kivipelto, Miia %A Knibbs, Luke D %A Knudsen, Ann Kristin %A Kokubo, Yoshihiro %A Kose, M Rifat %A Kosen, Soewarta %A Kraemer, Alexander %A Kravchenko, Michael %A Krishnaswami, Sanjay %A Kromhout, Hans %A Ku, Tiffany %A Kuate Defo, Barthelemy %A Kucuk Bicer, Burcu %A Kuipers, Ernst J %A Kulkarni, Chanda %A Kulkarni, Veena S %A Kumar, G Anil %A Kwan, Gene F %A Lai, Taavi %A Lakshmana Balaji, Arjun %A Lalloo, Ratilal %A Lallukka, Tea %A Lam, Hilton %A Lan, Qing %A Lansingh, Van C %A Larson, Heidi J %A Larsson, Anders %A Laryea, Dennis O %A Lavados, Pablo M %A Lawrynowicz, Alicia E %A Leasher, Janet L %A Lee, Jong-Tae %A Leigh, James %A Leung, Ricky %A Levi, Miriam %A Li, Yichong %A Li, Yongmei %A Liang, Juan %A Liang, Xiaofeng %A Lim, Stephen S %A Lindsay, M Patrice %A Lipshultz, Steven E %A Liu, Shiwei %A Liu, Yang %A Lloyd, Belinda K %A Logroscino, Giancarlo %A London, Stephanie J %A Lopez, Nancy %A Lortet-Tieulent, Joannie %A Lotufo, Paulo A %A Lozano, Rafael %A Lunevicius, Raimundas %A Ma, Jixiang %A Ma, Stefan %A Machado, Vasco M P %A MacIntyre, Michael F %A Magis-Rodriguez, Carlos %A Mahdi, Abbas A %A Majdan, Marek %A Malekzadeh, Reza %A Mangalam, Srikanth %A Mapoma, Christopher C %A Marape, Marape %A Marcenes, Wagner %A Margolis, David J %A Margono, Christopher %A Marks, Guy B %A Martin, Randall V %A Marzan, Melvin B %A Mashal, Mohammad T %A Masiye, Felix %A Mason-Jones, Amanda J %A Matsushita, Kunihiro %A Matzopoulos, Richard %A Mayosi, Bongani M %A Mazorodze, Tasara T %A McKay, Abigail C %A McKee, Martin %A McLain, Abigail %A Meaney, Peter A %A Medina, Catalina %A Mehndiratta, Man Mohan %A Mejia-Rodriguez, Fabiola %A Mekonnen, Wubegzier %A Melaku, Yohannes A %A Meltzer, Michele %A Memish, Ziad A %A Mendoza, Walter %A Mensah, George A %A Meretoja, Atte %A Mhimbira, Francis Apolinary %A Micha, Renata %A Miller, Ted R %A Mills, Edward J %A Misganaw, Awoke %A Mishra, Santosh %A Mohamed Ibrahim, Norlinah %A Mohammad, Karzan A %A Mokdad, Ali H %A Mola, Glen L %A Monasta, Lorenzo %A Montañez Hernandez, Julio C %A Montico, Marcella %A Moore, Ami R %A Morawska, Lidia %A Mori, Rintaro %A Moschandreas, Joanna %A Moturi, Wilkister N %A Mozaffarian, Dariush %A Mueller, Ulrich O %A Mukaigawara, Mitsuru %A Mullany, Erin C %A Murthy, Kinnari S %A Naghavi, Mohsen %A Nahas, Ziad %A Naheed, Aliya %A Naidoo, Kovin S %A Naldi, Luigi %A Nand, Devina %A Nangia, Vinay %A Narayan, K M Venkat %A Nash, Denis %A Neal, Bruce %A Nejjari, Chakib %A Neupane, Sudan P %A Newton, Charles R %A Ngalesoni, Frida N %A Ngirabega, Jean de Dieu %A Nguyen, Grant %A Nguyen, Nhung T %A Nieuwenhuijsen, Mark J %A Nisar, Muhammad I %A Nogueira, José R %A Nolla, Joan M %A Nolte, Sandra %A Norheim, Ole F %A Norman, Rosana E %A Norrving, Bo %A Nyakarahuka, Luke %A Oh, In-Hwan %A Ohkubo, Takayoshi %A Olusanya, Bolajoko O %A Omer, Saad B %A Opio, John Nelson %A Orozco, Ricardo %A Pagcatipunan, Rodolfo S %A Pain, Amanda W %A Pandian, Jeyaraj D %A Panelo, Carlo Irwin A %A Papachristou, Christina %A Park, Eun-Kee %A Parry, Charles D %A Paternina Caicedo, Angel J %A Patten, Scott B %A Paul, Vinod K %A Pavlin, Boris I %A Pearce, Neil %A Pedraza, Lilia S %A Pedroza, Andrea %A Pejin Stokic, Ljiljana %A Pekericli, Ayfer %A Pereira, David M %A Perez-Padilla, Rogelio %A Perez-Ruiz, Fernando %A Perico, Norberto %A Perry, Samuel A L %A Pervaiz, Aslam %A Pesudovs, Konrad %A Peterson, Carrie B %A Petzold, Max %A Phillips, Michael R %A Phua, Hwee Pin %A Plass, Dietrich %A Poenaru, Dan %A Polanczyk, Guilherme V %A Polinder, Suzanne %A Pond, Constance D %A Pope, C Arden %A Pope, Daniel %A Popova, Svetlana %A Pourmalek, Farshad %A Powles, John %A Prabhakaran, Dorairaj %A Prasad, Noela M %A Qato, Dima M %A Quezada, Amado D %A Quistberg, D Alex A %A Racapé, Lionel %A Rafay, Anwar %A Rahimi, Kazem %A Rahimi-Movaghar, Vafa %A Rahman, Sajjad Ur %A Raju, Murugesan %A Rakovac, Ivo %A Rana, Saleem M %A Rao, Mayuree %A Razavi, Homie %A Reddy, K Srinath %A Refaat, Amany H %A Rehm, Jürgen %A Remuzzi, Giuseppe %A Ribeiro, Antonio L %A Riccio, Patricia M %A Richardson, Lee %A Riederer, Anne %A Robinson, Margaret %A Roca, Anna %A Rodriguez, Alina %A Rojas-Rueda, David %A Romieu, Isabelle %A Ronfani, Luca %A Room, Robin %A Roy, Nobhojit %A Ruhago, George M %A Rushton, Lesley %A Sabin, Nsanzimana %A Sacco, Ralph L %A Saha, Sukanta %A Sahathevan, Ramesh %A Sahraian, Mohammad Ali %A Salomon, Joshua A %A Salvo, Deborah %A Sampson, Uchechukwu K %A Sanabria, Juan R %A Sanchez, Luz Maria %A Sánchez-Pimienta, Tania G %A Sanchez-Riera, Lidia %A Sandar, Logan %A Santos, Itamar S %A Sapkota, Amir %A Satpathy, Maheswar %A Saunders, James E %A Sawhney, Monika %A Saylan, Mete I %A Scarborough, Peter %A Schmidt, Jürgen C %A Schneider, Ione J C %A Schöttker, Ben %A Schwebel, David C %A Scott, James G %A Seedat, Soraya %A Sepanlou, Sadaf G %A Serdar, Berrin %A Servan-Mori, Edson E %A Shaddick, Gavin %A Shahraz, Saeid %A Levy, Teresa Shamah %A Shangguan, Siyi %A She, Jun %A Sheikhbahaei, Sara %A Shibuya, Kenji %A Shin, Hwashin H %A Shinohara, Yukito %A Shiri, Rahman %A Shishani, Kawkab %A Shiue, Ivy %A Sigfusdottir, Inga D %A Silberberg, Donald H %A Simard, Edgar P %A Sindi, Shireen %A Singh, Abhishek %A Singh, Gitanjali M %A Singh, Jasvinder A %A Skirbekk, Vegard %A Sliwa, Karen %A Soljak, Michael %A Soneji, Samir %A Søreide, Kjetil %A Soshnikov, Sergey %A Sposato, Luciano A %A Sreeramareddy, Chandrashekhar T %A Stapelberg, Nicolas J C %A Stathopoulou, Vasiliki %A Steckling, Nadine %A Stein, Dan J %A Stein, Murray B %A Stephens, Natalie %A Stöckl, Heidi %A Straif, Kurt %A Stroumpoulis, Konstantinos %A Sturua, Lela %A Sunguya, Bruno F %A Swaminathan, Soumya %A Swaroop, Mamta %A Sykes, Bryan L %A Tabb, Karen M %A Takahashi, Ken %A Talongwa, Roberto T %A Tandon, Nikhil %A Tanne, David %A Tanner, Marcel %A Tavakkoli, Mohammad %A Te Ao, Braden J %A Teixeira, Carolina M %A Téllez Rojo, Martha M %A Terkawi, Abdullah S %A Texcalac-Sangrador, José Luis %A Thackway, Sarah V %A Thomson, Blake %A Thorne-Lyman, Andrew L %A Thrift, Amanda G %A Thurston, George D %A Tillmann, Taavi %A Tobollik, Myriam %A Tonelli, Marcello %A Topouzis, Fotis %A Towbin, Jeffrey A %A Toyoshima, Hideaki %A Traebert, Jefferson %A Tran, Bach X %A Trasande, Leonardo %A Trillini, Matias %A Trujillo, Ulises %A Dimbuene, Zacharie Tsala %A Tsilimbaris, Miltiadis %A Tuzcu, Emin Murat %A Uchendu, Uche S %A Ukwaja, Kingsley N %A Uzun, Selen B %A van de Vijver, Steven %A Van Dingenen, Rita %A van Gool, Coen H %A van Os, Jim %A Varakin, Yuri Y %A Vasankari, Tommi J %A Vasconcelos, Ana Maria N %A Vavilala, Monica S %A Veerman, Lennert J %A Velasquez-Melendez, Gustavo %A Venketasubramanian, N %A Vijayakumar, Lakshmi %A Villalpando, Salvador %A Violante, Francesco S %A Vlassov, Vasiliy Victorovich %A Vollset, Stein Emil %A Wagner, Gregory R %A Waller, Stephen G %A Wallin, Mitchell T %A Wan, Xia %A Wang, Haidong %A Wang, JianLi %A Wang, Linhong %A Wang, Wenzhi %A Wang, Yanping %A Warouw, Tati S %A Watts, Charlotte H %A Weichenthal, Scott %A Weiderpass, Elisabete %A Weintraub, Robert G %A Werdecker, Andrea %A Wessells, K Ryan %A Westerman, Ronny %A Whiteford, Harvey A %A Wilkinson, James D %A Williams, Hywel C %A Williams, Thomas N %A Woldeyohannes, Solomon M %A Wolfe, Charles D A %A Wong, John Q %A Woolf, Anthony D %A Wright, Jonathan L %A Wurtz, Brittany %A Xu, Gelin %A Yan, Lijing L %A Yang, Gonghuan %A Yano, Yuichiro %A Ye, Pengpeng %A Yenesew, Muluken %A Yentür, Gökalp K %A Yip, Paul %A Yonemoto, Naohiro %A Yoon, Seok-Jun %A Younis, Mustafa Z %A Younoussi, Zourkaleini %A Yu, Chuanhua %A Zaki, Maysaa E %A Zhao, Yong %A Zheng, Yingfeng %A Zhou, Maigeng %A Zhu, Jun %A Zhu, Shankuan %A Zou, Xiaonong %A Zunt, Joseph R %A Lopez, Alan D %A Vos, Theo %A Murray, Christopher J %X

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.

%B Lancet %V 386 %P 2287-323 %8 2015 Dec 5 %G eng %N 10010 %1 http://www.ncbi.nlm.nih.gov/pubmed/26364544?dopt=Abstract %R 10.1016/S0140-6736(15)00128-2 %0 Journal Article %J Lancet %D 2015 %T 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. %A Murray, Christopher J L %A Barber, Ryan M %A Foreman, Kyle J %A Abbasoglu Ozgoren, Ayse %A Abd-Allah, Foad %A Abera, Semaw F %A Aboyans, Victor %A Abraham, Jerry P %A Abubakar, Ibrahim %A Abu-Raddad, Laith J %A Abu-Rmeileh, Niveen M %A Achoki, Tom %A Ackerman, Ilana N %A Ademi, Zanfina %A Adou, Arsène K %A Adsuar, José C %A Afshin, Ashkan %A Agardh, Emilie E %A Alam, Sayed Saidul %A Alasfoor, Deena %A Albittar, Mohammed I %A Alegretti, Miguel A %A Alemu, Zewdie A %A Alfonso-Cristancho, Rafael %A Alhabib, Samia %A Ali, Raghib %A Alla, François %A Allebeck, Peter %A AlMazroa, Mohammad A %A 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%A Phillips, Bryan K %A Phillips, David E %A Piel, Frédéric B %A Plass, Dietrich %A Poenaru, Dan %A Polinder, Suzanne %A Pope, Daniel %A Popova, Svetlana %A Poulton, Richie G %A Pourmalek, Farshad %A Prabhakaran, Dorairaj %A Prasad, Noela M %A Pullan, Rachel L %A Qato, Dima M %A Quistberg, D Alex %A Rafay, Anwar %A Rahimi, Kazem %A Rahman, Sajjad U %A Raju, Murugesan %A Rana, Saleem M %A Razavi, Homie %A Reddy, K Srinath %A Refaat, Amany %A Remuzzi, Giuseppe %A Resnikoff, Serge %A Ribeiro, Antonio L %A Richardson, Lee %A Richardus, Jan Hendrik %A Roberts, D Allen %A Rojas-Rueda, David %A Ronfani, Luca %A Roth, Gregory A %A Rothenbacher, Dietrich %A Rothstein, David H %A Rowley, Jane T %A Roy, Nobhojit %A Ruhago, George M %A Saeedi, Mohammad Y %A Saha, Sukanta %A Sahraian, Mohammad Ali %A Sampson, Uchechukwu K A %A Sanabria, Juan R %A Sandar, Logan %A Santos, Itamar S %A Satpathy, Maheswar %A Sawhney, Monika %A Scarborough, Peter %A Schneider, Ione J %A Schöttker, Ben %A Schumacher, Austin E %A Schwebel, David C %A Scott, James G %A Seedat, Soraya %A Sepanlou, Sadaf G %A Serina, Peter T %A Servan-Mori, Edson E %A Shackelford, Katya A %A Shaheen, Amira %A Shahraz, Saeid %A Shamah Levy, Teresa %A Shangguan, Siyi %A She, Jun %A Sheikhbahaei, Sara %A Shi, Peilin %A Shibuya, Kenji %A Shinohara, Yukito %A Shiri, Rahman %A Shishani, Kawkab %A Shiue, Ivy %A Shrime, Mark G %A Sigfusdottir, Inga D %A Silberberg, Donald H %A Simard, Edgar P %A Sindi, Shireen %A Singh, Abhishek %A Singh, Jasvinder A %A Singh, Lavanya %A Skirbekk, Vegard %A Slepak, Erica Leigh %A Sliwa, Karen %A Soneji, Samir %A Søreide, Kjetil %A Soshnikov, Sergey %A Sposato, Luciano A %A Sreeramareddy, Chandrashekhar T %A Stanaway, Jeffrey D %A Stathopoulou, Vasiliki %A Stein, Dan J %A Stein, Murray B %A Steiner, Caitlyn %A Steiner, Timothy J %A Stevens, Antony %A Stewart, Andrea %A Stovner, Lars J %A Stroumpoulis, Konstantinos %A Sunguya, Bruno F %A Swaminathan, Soumya %A Swaroop, Mamta %A Sykes, Bryan L %A Tabb, Karen M %A Takahashi, Ken %A Tandon, Nikhil %A Tanne, David %A Tanner, Marcel %A Tavakkoli, Mohammad %A Taylor, Hugh R %A Te Ao, Braden J %A Tediosi, Fabrizio %A Temesgen, Awoke M %A Templin, Tara %A Ten Have, Margreet %A Tenkorang, Eric Y %A Terkawi, Abdullah S %A Thomson, Blake %A Thorne-Lyman, Andrew L %A Thrift, Amanda G %A Thurston, George D %A Tillmann, Taavi %A Tonelli, Marcello %A Topouzis, Fotis %A Toyoshima, Hideaki %A Traebert, Jefferson %A Tran, Bach X %A Trillini, Matias %A Truelsen, Thomas %A Tsilimbaris, Miltiadis %A Tuzcu, Emin M %A Uchendu, Uche S %A Ukwaja, Kingsley N %A Undurraga, Eduardo A %A Uzun, Selen B %A Van Brakel, Wim H %A van de Vijver, Steven %A van Gool, Coen H %A van Os, Jim %A Vasankari, Tommi J %A Venketasubramanian, N %A Violante, Francesco S %A Vlassov, Vasiliy V %A Vollset, Stein Emil %A Wagner, Gregory R %A Wagner, Joseph %A Waller, Stephen G %A Wan, Xia %A Wang, Haidong %A Wang, JianLi %A Wang, Linhong %A Warouw, Tati S %A Weichenthal, Scott %A Weiderpass, Elisabete %A Weintraub, Robert G %A Wenzhi, Wang %A Werdecker, Andrea %A Westerman, Ronny %A Whiteford, Harvey A %A Wilkinson, James D %A Williams, Thomas N %A Wolfe, Charles D %A Wolock, Timothy M %A Woolf, Anthony D %A Wulf, Sarah %A Wurtz, Brittany %A Xu, Gelin %A Yan, Lijing L %A Yano, Yuichiro %A Ye, Pengpeng %A Yentür, Gökalp K %A Yip, Paul %A Yonemoto, Naohiro %A Yoon, Seok-Jun %A Younis, Mustafa Z %A Yu, Chuanhua %A Zaki, Maysaa E %A Zhao, Yong %A Zheng, Yingfeng %A Zonies, David %A Zou, Xiaonong %A Salomon, Joshua A %A Lopez, Alan D %A Vos, Theo %K Aged %K Chronic Disease %K Communicable Diseases %K Female %K Global Health %K Health Transition %K Humans %K Life Expectancy %K Male %K Middle Aged %K Mortality, Premature %K Quality-Adjusted Life Years %K Socioeconomic Factors %K Wounds and Injuries %X

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.

%B Lancet %V 386 %P 2145-91 %8 2015 Nov 28 %G eng %N 10009 %1 http://www.ncbi.nlm.nih.gov/pubmed/26321261?dopt=Abstract %R 10.1016/S0140-6736(15)61340-X %0 Journal Article %J Lancet %D 2014 %T 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. %A Wang, Haidong %A Liddell, Chelsea A %A Coates, Matthew M %A Mooney, Meghan D %A Levitz, Carly E %A Schumacher, Austin E %A Apfel, Henry %A Iannarone, Marissa %A Phillips, Bryan %A Lofgren, Katherine T %A Sandar, Logan %A Dorrington, Rob E %A Rakovac, Ivo %A Jacobs, Troy A %A Liang, Xiaofeng %A Zhou, Maigeng %A Zhu, Jun %A Yang, Gonghuan %A Wang, Yanping %A Liu, Shiwei %A Li, Yichong %A Ozgoren, Ayse Abbasoglu %A Abera, Semaw Ferede %A Abubakar, Ibrahim %A Achoki, Tom %A Adelekan, Ademola %A Ademi, Zanfina %A Alemu, Zewdie Aderaw %A Allen, Peter J %A AlMazroa, Mohammad AbdulAziz %A Alvarez, Elena %A Amankwaa, Adansi A %A Amare, Azmeraw T %A Ammar, Walid %A Anwari, Palwasha %A Cunningham, Solveig Argeseanu %A Asad, Majed Masoud %A Assadi, Reza %A Banerjee, Amitava %A Basu, Sanjay %A Bedi, Neeraj %A Bekele, Tolesa %A Bell, Michelle L %A Bhutta, Zulfiqar %A Blore, Jed D %A Basara, Berrak Bora %A Boufous, Soufiane %A Breitborde, Nicholas %A Bruce, Nigel G %A Bui, Linh Ngoc %A Carapetis, Jonathan R %A Cárdenas, Rosario %A Carpenter, David O %A Caso, Valeria %A Castro, Ruben Estanislao %A Catalá-López, Ferrán %A Cavlin, Alanur %A Che, Xuan %A Chiang, Peggy Pei-Chia %A Chowdhury, Rajiv %A Christophi, Costas A %A Chuang, Ting-Wu %A Cirillo, Massimo %A da Costa Leite, Iuri %A Courville, Karen J %A Dandona, Lalit %A Dandona, Rakhi %A Davis, Adrian %A Dayama, Anand %A Deribe, Kebede %A Dharmaratne, Samath D %A Dherani, Mukesh K %A Dilmen, Uğur %A Ding, Eric L %A Edmond, Karen M %A Ermakov, Sergei Petrovich %A Farzadfar, Farshad %A Fereshtehnejad, Seyed-Mohammad %A Fijabi, Daniel Obadare %A Foigt, Nataliya %A Forouzanfar, Mohammad H %A Garcia, Ana C %A Geleijnse, Johanna M %A Gessner, Bradford D %A Goginashvili, Ketevan %A Gona, Philimon %A Goto, Atsushi %A Gouda, Hebe N %A Green, Mark A %A Greenwell, Karen Fern %A Gugnani, Harish Chander %A Gupta, Rahul %A Hamadeh, Randah Ribhi %A Hammami, Mouhanad %A Harb, Hilda L %A Hay, Simon %A Hedayati, Mohammad T %A Hosgood, H Dean %A Hoy, Damian G %A Idrisov, Bulat T %A Islami, Farhad %A Ismayilova, Samaya %A Jha, Vivekanand %A Jiang, Guohong %A Jonas, Jost B %A Juel, Knud %A Kabagambe, Edmond Kato %A Kazi, Dhruv S %A Kengne, Andre Pascal %A Kereselidze, Maia %A Khader, Yousef Saleh %A Khalifa, Shams Eldin Ali Hassan %A Khang, Young-Ho %A Kim, Daniel %A Kinfu, Yohannes %A Kinge, Jonas M %A Kokubo, Yoshihiro %A Kosen, Soewarta %A Defo, Barthelemy Kuate %A Kumar, G Anil %A Kumar, Kaushalendra %A Kumar, Ravi B %A Lai, Taavi %A Lan, Qing %A Larsson, Anders %A Lee, Jong-Tae %A Leinsalu, Mall %A Lim, Stephen S %A Lipshultz, Steven E %A Logroscino, Giancarlo %A Lotufo, Paulo A %A Lunevicius, Raimundas %A Lyons, Ronan Anthony %A Ma, Stefan %A Mahdi, Abbas Ali %A Marzan, Melvin Barrientos %A Mashal, Mohammad Taufiq %A Mazorodze, Tasara T %A McGrath, John J %A Memish, Ziad A %A Mendoza, Walter %A Mensah, George A %A Meretoja, Atte %A Miller, Ted R %A Mills, Edward J %A Mohammad, Karzan Abdulmuhsin %A Mokdad, Ali H %A Monasta, Lorenzo %A Montico, Marcella %A Moore, Ami R %A Moschandreas, Joanna %A Msemburi, William T %A Mueller, Ulrich O %A Muszynska, Magdalena M %A Naghavi, Mohsen %A Naidoo, Kovin S %A Narayan, K M Venkat %A Nejjari, Chakib %A Ng, Marie %A de Dieu Ngirabega, Jean %A Nieuwenhuijsen, Mark J %A Nyakarahuka, Luke %A Ohkubo, Takayoshi %A Omer, Saad B %A Caicedo, Angel J Paternina %A Pillay-van Wyk, Victoria %A Pope, Dan %A Pourmalek, Farshad %A Prabhakaran, Dorairaj %A Rahman, Sajjad U R %A Rana, Saleem M %A Reilly, Robert Quentin %A Rojas-Rueda, David %A Ronfani, Luca %A Rushton, Lesley %A Saeedi, Mohammad Yahya %A Salomon, Joshua A %A Sampson, Uchechukwu %A Santos, Itamar S %A Sawhney, Monika %A Schmidt, Jürgen C %A Shakh-Nazarova, Marina %A She, Jun %A Sheikhbahaei, Sara %A Shibuya, Kenji %A Shin, Hwashin Hyun %A Shishani, Kawkab %A Shiue, Ivy %A Sigfusdottir, Inga Dora %A Singh, Jasvinder A %A Skirbekk, Vegard %A Sliwa, Karen %A Soshnikov, Sergey S %A Sposato, Luciano A %A Stathopoulou, Vasiliki Kalliopi %A Stroumpoulis, Konstantinos %A Tabb, Karen M %A Talongwa, Roberto Tchio %A Teixeira, Carolina Maria %A Terkawi, Abdullah Sulieman %A Thomson, Alan J %A Thorne-Lyman, Andrew L %A Toyoshima, Hideaki %A Dimbuene, Zacharie Tsala %A Uwaliraye, Parfait %A Uzun, Selen Begüm %A Vasankari, Tommi J %A Vasconcelos, Ana Maria Nogales %A Vlassov, Vasiliy Victorovich %A Vollset, Stein Emil %A Waller, Stephen %A Wan, Xia %A Weichenthal, Scott %A Weiderpass, Elisabete %A Weintraub, Robert G %A Westerman, Ronny %A Wilkinson, James D %A Williams, Hywel C %A Yang, Yang C %A Yentur, Gokalp Kadri %A Yip, Paul %A Yonemoto, Naohiro %A Younis, Mustafa %A Yu, Chuanhua %A Jin, Kim Yun %A El Sayed Zaki, Maysaa %A Zhu, Shankuan %A Vos, Theo %A Lopez, Alan D %A Murray, Christopher J L %K Child Mortality %K Child, Preschool %K Global Health %K Humans %K Infant %K Infant Mortality %K Infant, Newborn %K Organizational Objectives %K Risk Factors %K Socioeconomic Factors %X

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.

%B Lancet %V 384 %P 957-79 %8 2014 Sep 13 %G eng %N 9947 %1 http://www.ncbi.nlm.nih.gov/pubmed/24797572?dopt=Abstract %R 10.1016/S0140-6736(14)60497-9