Six new loci associated with body mass index highlight a neuronal influence on body weight regulation.

TitleSix new loci associated with body mass index highlight a neuronal influence on body weight regulation.
Publication TypeJournal Article
Year of Publication2009
AuthorsWiller, CJ, Speliotes, EK, Loos, RJF, Li, S, Lindgren, CM, Heid, IM, Berndt, SI, Elliott, AL, Jackson, AU, Lamina, C, Lettre, G, Lim, N, Lyon, HN, McCarroll, SA, Papadakis, K, Qi, L, Randall, JC, Roccasecca, RMaria, Sanna, S, Scheet, P, Weedon, MN, Wheeler, E, Zhao, JHua, Jacobs, LC, Prokopenko, I, Soranzo, N, Tanaka, T, Timpson, NJ, Almgren, P, Bennett, A, Bergman, RN, Bingham, SA, Bonnycastle, LL, Brown, M, Burtt, NP, Chines, P, Coin, L, Collins, FS, Connell, JM, Cooper, C, Smith, GDavey, Dennison, EM, Deodhar, P, Elliott, P, Erdos, MR, Estrada, K, Evans, DM, Gianniny, L, Gieger, C, Gillson, CJ, Guiducci, C, Hackett, R, Hadley, D, Hall, AS, Havulinna, AS, Hebebrand, J, Hofman, A, Isomaa, B, Jacobs, KB, Johnson, T, Jousilahti, P, Jovanovic, Z, Khaw, K-T, Kraft, P, Kuokkanen, M, Kuusisto, J, Laitinen, J, Lakatta, EG, Luan, J'an, Luben, RN, Mangino, M, McArdle, WL, Meitinger, T, Mulas, A, Munroe, PB, Narisu, N, Ness, AR, Northstone, K, O'Rahilly, S, Purmann, C, Rees, MG, Ridderstrale, M, Ring, SM, Rivadeneira, F, Ruokonen, A, Sandhu, MS, Saramies, J, Scott, LJ, Scuteri, A, Silander, K, Sims, MA, Song, K, Stephens, J, Stevens, S, Stringham, HM, Tung, YCLoraine, Valle, TT, Van Duijn, CM, Vimaleswaran, KS, Vollenweider, P, Waeber, G, Wallace, C, Watanabe, RM, Waterworth, DM, Watkins, N, Witteman, JCM, Zeggini, E, Zhai, G, M Zillikens, C, Altshuler, D, Caulfield, MJ, Chanock, SJ, I Farooqi, S, Ferrucci, L, Guralnik, JM, Hattersley, AT, Hu, FB, Jarvelin, M-R, Laakso, M, Mooser, V, Ong, KK, Ouwehand, WH, Salomaa, V, Samani, NJ, Spector, TD, Tuomi, T, Tuomilehto, J, Uda, M, Uitterlinden, AG, Wareham, NJ, Deloukas, P, Frayling, TM, Groop, LC, Hayes, RB, Hunter, DJ, Mohlke, KL, Peltonen, L, Schlessinger, D, Strachan, DP, Wichmann, H-E, McCarthy, MI, Boehnke, M, Barroso, I, Abecasis, GR, Hirschhorn, JN
Corporate Authors,
JournalNat Genet
Volume41
Issue1
Pagination25-34
Date Published2009 Jan
ISSN1546-1718
KeywordsAlleles, Anthropometry, Body Mass Index, Body Weight, Central Nervous System, Cohort Studies, Gene Dosage, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Meta-Analysis as Topic, Obesity, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Quantitative Trait, Heritable
Abstract

Common variants at only two loci, FTO and MC4R, have been reproducibly associated with body mass index (BMI) in humans. To identify additional loci, we conducted meta-analysis of 15 genome-wide association studies for BMI (n > 32,000) and followed up top signals in 14 additional cohorts (n > 59,000). We strongly confirm FTO and MC4R and identify six additional loci (P < 5 x 10(-8)): TMEM18, KCTD15, GNPDA2, SH2B1, MTCH2 and NEGR1 (where a 45-kb deletion polymorphism is a candidate causal variant). Several of the likely causal genes are highly expressed or known to act in the central nervous system (CNS), emphasizing, as in rare monogenic forms of obesity, the role of the CNS in predisposition to obesity.

DOI10.1038/ng.287
Alternate JournalNat. Genet.
Citation Key10.1038/ng.287
PubMed ID19079261
PubMed Central IDPMC2695662
Grant ListR01 CA050385 / CA / NCI NIH HHS / United States
01-HG-65403 / HG / NHGRI NIH HHS / United States
FS/05/061/19501 / / British Heart Foundation / United Kingdom
G9521010 / / Medical Research Council / United Kingdom
5UO1CA098233 / CA / NCI NIH HHS / United States
G0000649 / / Medical Research Council / United Kingdom
K23 DK080145 / DK / NIDDK NIH HHS / United States
DK075787 / DK / NIDDK NIH HHS / United States
082390 / / Wellcome Trust / United Kingdom
G0400874 / / Medical Research Council / United Kingdom
T32DK07191 / DK / NIDDK NIH HHS / United States
R56 DK062370 / DK / NIDDK NIH HHS / United States
N01HG65403 / HG / NHGRI NIH HHS / United States
MC_U147585827 / / Medical Research Council / United Kingdom
079557 / / Wellcome Trust / United Kingdom
U01 HL084729 / HL / NHLBI NIH HHS / United States
G0600705 / / Medical Research Council / United Kingdom
P01 CA087969 / CA / NCI NIH HHS / United States
T32 DK007191 / DK / NIDDK NIH HHS / United States
R01 HL087679 / HL / NHLBI NIH HHS / United States
G0800582 / / Medical Research Council / United Kingdom
R01 CA067262 / CA / NCI NIH HHS / United States
N01-AG-1-2109 / AG / NIA NIH HHS / United States
R01 HG002651 / HG / NHGRI NIH HHS / United States
HL087679 / HL / NHLBI NIH HHS / United States
K23 DK080145-01 / DK / NIDDK NIH HHS / United States
U.1475.00.003.00010.02 (85819) / / Medical Research Council / United Kingdom
1Z01 HG000024 / HG / NHGRI NIH HHS / United States
R01 DK072193 / DK / NIDDK NIH HHS / United States
CA87969 / CA / NCI NIH HHS / United States
MC_U147585819 / / Medical Research Council / United Kingdom
MC_U105630924 / / Medical Research Council / United Kingdom
F32 DK079466 / DK / NIDDK NIH HHS / United States
077011 / / Wellcome Trust / United Kingdom
R01 DK075787 / DK / NIDDK NIH HHS / United States
CA49449 / CA / NCI NIH HHS / United States
U01 CA067262 / CA / NCI NIH HHS / United States
R01 CA065725 / CA / NCI NIH HHS / United States
077016 / / Wellcome Trust / United Kingdom
CA67262 / CA / NCI NIH HHS / United States
R01 DK062370 / DK / NIDDK NIH HHS / United States
1RL1MH083268 / MH / NIMH NIH HHS / United States
K23 DK067288 / DK / NIDDK NIH HHS / United States
MC_UP_A620_1014 / / Medical Research Council / United Kingdom
DK072193 / DK / NIDDK NIH HHS / United States
MC_U106179471 / / Medical Research Council / United Kingdom
F32 DK079466-01 / DK / NIDDK NIH HHS / United States
HL084729 / HL / NHLBI NIH HHS / United States
076113 / / Wellcome Trust / United Kingdom
/ / Intramural NIH HHS / United States
R01 DK029867 / DK / NIDDK NIH HHS / United States
MC_U106179472 / / Medical Research Council / United Kingdom
G0401527 / / Medical Research Council / United Kingdom
G0701863 / / Medical Research Council / United Kingdom
090532 / / Wellcome Trust / United Kingdom
U01 CA098233 / CA / NCI NIH HHS / United States
U01 DK062370 / DK / NIDDK NIH HHS / United States
HG02651 / HG / NHGRI NIH HHS / United States
G9824984 / / Medical Research Council / United Kingdom
DK062370 / DK / NIDDK NIH HHS / United States
076467/Z/05/Z / / Wellcome Trust / United Kingdom
089061 / / Wellcome Trust / United Kingdom
068545/Z/02 / / Wellcome Trust / United Kingdom
R01 CA049449 / CA / NCI NIH HHS / United States
CA50385 / CA / NCI NIH HHS / United States
RL1 MH083268 / MH / NIMH NIH HHS / United States
Z01 HG000024 / HG / NHGRI NIH HHS / United States
U01 CA049449 / CA / NCI NIH HHS / United States
G0400491 / / Medical Research Council / United Kingdom
MC_U106188470 / / Medical Research Council / United Kingdom
G0000934 / / Medical Research Council / United Kingdom
MC_U147585824 / / Medical Research Council / United Kingdom
G0601261 / / Medical Research Council / United Kingdom
CA65725 / CA / NCI NIH HHS / United States
G9815508 / / Medical Research Council / United Kingdom