Genetic studies of body mass index yield new insights for obesity biology.

TitleGenetic studies of body mass index yield new insights for obesity biology.
Publication TypeJournal Article
Year of Publication2015
AuthorsLocke, AE, Kahali, B, Berndt, SI, Justice, AE, Pers, TH, Day, FR, Powell, C, Vedantam, S, Buchkovich, ML, Yang, J, Croteau-Chonka, DC, Esko, T, Fall, T, Ferreira, T, Gustafsson, S, Kutalik, Z, Luan, J'an, Mägi, R, Randall, JC, Winkler, TW, Wood, AR, Workalemahu, T, Faul, JD, Smith, JA, Zhao, JHua, Zhao, W, Chen, J, Fehrmann, R, Hedman, ÅK, Karjalainen, J, Schmidt, EM, Absher, D, Amin, N, Anderson, D, Beekman, M, Bolton, JL, Bragg-Gresham, JL, Buyske, S, Demirkan, A, Deng, G, Ehret, G, Feenstra, B, Feitosa, MF, Fischer, K, Goel, A, Gong, J, Jackson, AU, Kanoni, S, Kleber, ME, Kristiansson, K, Lim, U, Lotay, V, Mangino, M, Leach, IMateo, Medina-Gomez, C, Medland, SE, Nalls, MA, Palmer, CD, Pasko, D, Pechlivanis, S, Peters, MJ, Prokopenko, I, Shungin, D, Stančáková, A, Strawbridge, RJ, Sung, YJu, Tanaka, T, Teumer, A, Trompet, S, van der Laan, SW, van Setten, J, Van Vliet-Ostaptchouk, JV, Wang, Z, Yengo, L, Zhang, W, Isaacs, A, Albrecht, E, Ärnlöv, J, Arscott, GM, Attwood, AP, Bandinelli, S, Barrett, A, Bas, IN, Bellis, C, Bennett, AJ, Berne, C, Blagieva, R, Blüher, M, Böhringer, S, Bonnycastle, LL, Böttcher, Y, Boyd, HA, Bruinenberg, M, Caspersen, IH, Chen, Y-DI, Clark, R, E Daw, W, de Craen, AJM, Delgado, G, Dimitriou, M, Doney, ASF, Eklund, N, Estrada, K, Eury, E, Folkersen, L, Fraser, RM, Garcia, ME, Geller, F, Giedraitis, V, Gigante, B, Go, AS, Golay, A, Goodall, AH, Gordon, SD, Gorski, M, Grabe, H-J, Grallert, H, Grammer, TB, Gräßler, J, Grönberg, H, Groves, CJ, Gusto, G, Haessler, J, Hall, P, Haller, T, Hallmans, G, Hartman, CA, Hassinen, M, Hayward, C, Heard-Costa, NL, Helmer, Q, Hengstenberg, C, Holmen, O, Hottenga, J-J, James, AL, Jeff, JM, Johansson, Å, Jolley, J, Juliusdottir, T, Kinnunen, L, Koenig, W, Koskenvuo, M, Kratzer, W, Laitinen, J, Lamina, C, Leander, K, Lee, NR, Lichtner, P, Lars Lind, Lindström, J, Lo, KS, Lobbens, S, Lorbeer, R, Lu, Y, Mach, F, Magnusson, PKE, Mahajan, A, McArdle, WL, McLachlan, S, Menni, C, Merger, S, Mihailov, E, Milani, L, Moayyeri, A, Monda, KL, Morken, MA, Mulas, A, Müller, G, Müller-Nurasyid, M, Musk, AW, Nagaraja, R, Nöthen, MM, Nolte, IM, Pilz, S, Rayner, NW, Renstrom, F, Rettig, R, Ried, JS, Ripke, S, Robertson, N, Rose, LM, Sanna, S, Scharnagl, H, Scholtens, S, Schumacher, FR, Scott, WR, Seufferlein, T, Shi, J, Smith, AVernon, Smolonska, J, Stanton, AV, Steinthorsdottir, V, Stirrups, K, Stringham, HM, Sundström, J, Swertz, MA, Swift, AJ, Syvänen, A-C, Tan, S-T, Tayo, B, Thorand, B, Thorleifsson, G, Tyrer, JP, Uh, H-W, Vandenput, L, Verhulst, FC, Vermeulen, SH, Verweij, N, Vonk, JM, Waite, LL, Warren, HR, Waterworth, D, Weedon, MN, Wilkens, LR, Willenborg, C, Wilsgaard, T, Wojczynski, MK, Wong, A, Wright, AF, Zhang, Q, Brennan, EP, Choi, M, Dastani, Z, Drong, A, Eriksson, P, Franco-Cereceda, A, Gådin, JR, Gharavi, AG, Goddard, ME, Handsaker, RE, Huang, J, Karpe, F, Kathiresan, S, Keildson, S, Kiryluk, K, Kubo, M, Lee, J-Y, Liang, L, Lifton, RP, Ma, B, McCarroll, SA, McKnight, AJ, Min, JL, Moffatt, MF, Montgomery, GW, Murabito, JM, Nicholson, G, Nyholt, DR, Okada, Y, Perry, JRB, Dorajoo, R, Reinmaa, E, Salem, RM, Sandholm, N, Scott, RA, Stolk, L, Takahashi, A, Tanaka, T, Hooft, FMVan't, Vinkhuyzen, AE, Westra, H-J, Zhang, W, Zondervan, KT, Heath, AC, Arveiler, D, Bakker, SJL, Beilby, J, Bergman, RN, Blangero, J, Bovet, P, Campbell, H, Caulfield, MJ, Cesana, G, Chakravarti, A, Chasman, DI, Chines, PS, Collins, FS, Crawford, DC, L Cupples, A, Cusi, D, Danesh, J, de Faire, U, Ruijter, HM, Dominiczak, AF, Erbel, R, Erdmann, J, Eriksson, JG, Farrall, M, Felix, SB, Ferrannini, E, Ferrières, J, Ford, I, Forouhi, NG, Forrester, T, Franco, OH, Gansevoort, RT, Gejman, PV, Gieger, C, Gottesman, O, Gudnason, V, Gyllensten, U, Hall, AS, Harris, TB, Hattersley, AT, Hicks, AA, Hindorff, LA, Hingorani, AD, Hofman, A, Homuth, G, G Hovingh, K, Humphries, SE, Hunt, SC, Hyppönen, E, Illig, T, Jacobs, KB, Järvelin, M-R, Jöckel, K-H, Johansen, B, Jousilahti, P, J Jukema, W, Jula, AM, Kaprio, J, Kastelein, JJP, Keinanen-Kiukaanniemi, SM, Kiemeney, LA, Knekt, P, Kooner, JS, Kooperberg, C, Kovacs, P, Kraja, AT, Kumari, M, Kuusisto, J, Lakka, TA, Langenberg, C, Le Marchand, L, Lehtimäki, T, Lyssenko, V, Männistö, S, Marette, A, Matise, TC, McKenzie, CA, McKnight, B, Moll, FL, Morris, AD, Morris, AP, Murray, JC, Nelis, M, Ohlsson, C, Oldehinkel, AJ, Ong, KK, Madden, PA, Pasterkamp, G, Peden, JF, Peters, A, Postma, DS, Pramstaller, PP, Price, JF, Qi, L, Raitakari, OT, Rankinen, T, Rao, DC, Rice, TK, Ridker, PM, Rioux, JD, Ritchie, MD, Rudan, I, Salomaa, V, Samani, N, Saramies, J, Sarzynski, MA, Schunkert, H, Schwarz, PEH, Sever, P, Shuldiner, AR, Sinisalo, J, Stolk, RP, Strauch, K, Tönjes, A, Trégouët, D-A, Tremblay, A, Tremoli, E, Virtamo, J, Vohl, M-C, Völker, U, Waeber, G, Willemsen, G, Witteman, JC, M Zillikens, C, Adair, LS, Amouyel, P, Asselbergs, FW, Assimes, TL, Bochud, M, Boehm, BO, Boerwinkle, E, Bornstein, SR, Bottinger, EP, Bouchard, C, Cauchi, S, Chambers, JC, Chanock, SJ, Cooper, RS, de Bakker, PIW, Dedoussis, G, Ferrucci, L, Franks, PW, Froguel, P, Groop, LC, Haiman, CA, Hamsten, A, Hui, J, Hunter, DJ, Hveem, K, Kaplan, RC, Kivimaki, M, Kuh, D, Laakso, M, Liu, Y, Martin, NG, März, W, Melbye, M, Metspalu, A, Moebus, S, Munroe, PB, Njølstad, I, Oostra, BA, Palmer, CNA, Pedersen, NL, Perola, M, Pérusse, L, Peters, U, Power, C, Quertermous, T, Rauramaa, R, Rivadeneira, F, Saaristo, TE, Saleheen, D, Sattar, N, Schadt, EE, Schlessinger, D, Slagboom, EP, Snieder, H, Spector, TD, Thorsteinsdottir, U, Stumvoll, M, Tuomilehto, J, Uitterlinden, AG, Uusitupa, M, van der Harst, P, Walker, M, Wallaschofski, H, Wareham, NJ, Watkins, H, Weir, DR, Wichmann, H-E, Wilson, JF, Zanen, P, Borecki, IB, Deloukas, P, Fox, CS, Heid, IM, O'Connell, JR, Strachan, DP, Stefansson, K, van Duijn, CM, Abecasis, G, Franke, LL, Frayling, TM, McCarthy, MI, Visscher, PM, Scherag, A, Willer, CJ, Boehnke, M, Mohlke, KL, Lindgren, CM, Beckmann, JS, Barroso, I, North, KE, Ingelsson, E, Hirschhorn, J, Loos, RJF, Speliotes, EK
Corporate AuthorsLifeLines Cohort Study, ADIPOGen Consortium, AGEN-BMI Working Group, CARDIOGRAMplusC4D Consortium, CKDGen Consortium, GLGC, ICBP, MAGIC Investigators, MuTHER Consortium, MIGen Consortium, PAGE Consortium, ReproGen Consortium, GENIE Consortium, International Endogene Consortium
JournalNature
Volume518
Issue7538
Pagination197-206
Date Published2015 Feb 12
ISSN Number1476-4687
KeywordsAdipogenesis, Age Factors, BMI, Continental Population Groups, Energy Metabolism, Europe, Female, Genome-Wide Association Study, Glutamic Acid, Humans, Insulin, Male, Obesity, Obesity, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Synapses
Abstract

Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.

DOI10.1038/nature14177
User Guide Notes

http://www.ncbi.nlm.nih.gov/pubmed/25673413?dopt=Abstract

Alternate JournalNature
Citation Key8882
PubMed ID25673413
PubMed Central IDPMC4382211
Grant ListR01 DK093757 / DK / NIDDK NIH HHS / United States
MC_UU_12012/1 / / Medical Research Council / United Kingdom
CZB/4/710 / / Chief Scientist Office / United Kingdom
G9521010 / / Medical Research Council / United Kingdom
G1001799 / / Medical Research Council / United Kingdom
CZB/4/672 / / Chief Scientist Office / United Kingdom
K23 DK080145 / DK / NIDDK NIH HHS / United States
098017 / / Wellcome Trust / United Kingdom
R21 DA027040 / DA / NIDA NIH HHS / United States
U01 HG007419 / HG / NHGRI NIH HHS / United States
R01 NS017950 / NS / NINDS NIH HHS / United States
R01 HL109946 / HL / NHLBI NIH HHS / United States
MC_UP_A100_1003 / / Medical Research Council / United Kingdom
T32 GM080178 / GM / NIGMS NIH HHS / United States
U01 AG009740 / AG / NIA NIH HHS / United States
085235 / / Wellcome Trust / United Kingdom
U01 HG007416 / HG / NHGRI NIH HHS / United States
RG/08/014/24067 / / British Heart Foundation / United Kingdom
R01 DK072193 / DK / NIDDK NIH HHS / United States
MC_UU_12019/1 / / Medical Research Council / United Kingdom
G1000143 / / Medical Research Council / United Kingdom
U01 HG007376 / HG / NHGRI NIH HHS / United States
R01 DK075787 / DK / NIDDK NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
MR/L003120/1 / / Medical Research Council / United Kingdom
R01 AG025941 / AG / NIA NIH HHS / United States
R01 AG041517 / AG / NIA NIH HHS / United States
MC_UU_12015/1 / / Medical Research Council / United Kingdom
R01 DK062370 / DK / NIDDK NIH HHS / United States
MC_U106179471 / / Medical Research Council / United Kingdom
P30 DK063491 / DK / NIDDK NIH HHS / United States
097117 / / Wellcome Trust / United Kingdom
MC_UU_12015/2 / / Medical Research Council / United Kingdom
TL1 TR001066 / TR / NCATS NIH HHS / United States
T32 HL007824 / HL / NHLBI NIH HHS / United States
P20 MD006899 / MD / NIMHD NIH HHS / United States
P30 DK072488 / DK / NIDDK NIH HHS / United States
K01 HL116770 / HL / NHLBI NIH HHS / United States
14136 / / Cancer Research UK / United Kingdom
MC_U106179472 / / Medical Research Council / United Kingdom
R01 AG033193 / AG / NIA NIH HHS / United States
MC_UU_12013/1 / / Medical Research Council / United Kingdom
P30 DK020541 / DK / NIDDK NIH HHS / United States
MC_PC_U127561128 / / Medical Research Council / United Kingdom
UM1 CA182913 / CA / NCI NIH HHS / United States
U01 DK062370 / DK / NIDDK NIH HHS / United States
P30 HL107251 / HL / NHLBI NIH HHS / United States
084766 / / Wellcome Trust / United Kingdom
100574 / / Wellcome Trust / United Kingdom
P30 GM103341 / GM / NIGMS NIH HHS / United States
R01 DK089256 / DK / NIDDK NIH HHS / United States
MR/K006584/1 / / Medical Research Council / United Kingdom
MR/K013351/1 / / Medical Research Council / United Kingdom
P30 DK020572 / DK / NIDDK NIH HHS / United States
MC_UU_12015/5 / / Medical Research Council / United Kingdom
P60 DK020541 / DK / NIDDK NIH HHS / United States
R01 HL117626 / HL / NHLBI NIH HHS / United States
098381 / / Wellcome Trust / United Kingdom
R01 HL117078 / HL / NHLBI NIH HHS / United States
UM1 CA182910 / CA / NCI NIH HHS / United States
T32 HL007055 / HL / NHLBI NIH HHS / United States
G0601261 / / Medical Research Council / United Kingdom
R01 DK078150 / DK / NIDDK NIH HHS / United States
UL1 TR001067 / TR / NCATS NIH HHS / United States
RG/10/12/28456 / / British Heart Foundation / United Kingdom
U01 AG049505 / AG / NIA NIH HHS / United States