Title | Genetic studies of body mass index yield new insights for obesity biology. |
Publication Type | Journal Article |
Year of Publication | 2015 |
Authors | Locke, 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, J, Smith, JA, Zhao, JHua, Zhao, W, Chen, J, Ferhmann, 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, GB, 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, OL, Hottenga, J-J, James, AL, Jeff, J, Johansson, Å, Jolley, J, Juliusdottir, T, Kinnunen, L, Koenig, W, Koskenvuo, M, Kratzer, W, Laitinen, J, Lamina, C, Leander, K, Lee, NR, Lichtner, P, Lind, L, Lindström, J, Lo, KSin, 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, NR, 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, KE, Stringham, HM, Sundström, J, Swertz, MA, Swift, AJ, Syvänen, A-C, Tan, S-T, Tayo, BO, Thorand, B, Thorleifsson, G, Tyrer, JP, Uh, H-W, Vandenput, L, Verhulst, FC, Vermeulen, SH, Verweij, N, Vonk, JM, Waite, LL, Warren, HR, Waterworth, DM, Weedon, MN, Wilkens, LR, Willenborg, C, Wilsgaard, T, Wojczynski, MK, Wong, A, Wright, AF, Zhang, Q, Brennan, EP, Choi, M, Dastani, Z, Drong, AW, 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, FM van 't, Vinkhuyzen, AAE, 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 den, 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, A, 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, PAF, 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, NJ, 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, Kivimäki, 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, T, 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, J, Strachan, DP, Stefansson, K, van Duijn, CM, Abecasis, GR, 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, Hirschhron, JN, Loos, RJF, Speliotes, EK |
Corporate Authors | LifeLines 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 |
Journal | Nature |
Volume | 518 |
Issue | 7538 |
Pagination | 197-206 |
Date Published | 2015 Feb 12 |
ISSN Number | 1476-4687 |
Keywords | Age Factors, BMI, Continental Population Groups, Energy Metabolism, Europe, Female, Genome-Wide Association Study, Glutamic Acid, Humans, Insulin, Male, 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. |
DOI | 10.1038/nature14177 |
User Guide Notes | |
Alternate Journal | Nature |
Citation Key | 8882 |
PubMed ID | 25673413 |
PubMed Central ID | PMC4382211 |
Grant List | 085235 / WT_ / Wellcome Trust / United Kingdom P30 CA071789 / CA / NCI NIH HHS / United States R01 DK093757 / DK / NIDDK NIH HHS / United States U01 HG007417 / HG / NHGRI NIH HHS / United States MC_UU_12012/1 / MRC_ / Medical Research Council / United Kingdom CZB/4/710 / CSO_ / Chief Scientist Office / United Kingdom G9521010 / MRC_ / Medical Research Council / United Kingdom G1001799 / MRC_ / Medical Research Council / United Kingdom CZB/4/672 / CSO_ / Chief Scientist Office / United Kingdom R21 DA027040 / DA / NIDA NIH HHS / United States K23 DK080145 / DK / NIDDK NIH HHS / United States 098017 / WT_ / Wellcome Trust / United Kingdom RG/08/008/25291 / BHF_ / British Heart Foundation / United Kingdom WT097117 / WT_ / Wellcome Trust / United Kingdom U01 HG007419 / HG / NHGRI NIH HHS / United States R01 NS017950 / NS / NINDS NIH HHS / United States T32 GM007814 / GM / NIGMS NIH HHS / United States MR/K002414/1 / MRC_ / Medical Research Council / United Kingdom BHF_RG/08/014/24067 / BHF_ / British Heart Foundation / United Kingdom R01 HL109946 / HL / NHLBI NIH HHS / United States MC_UP_A100_1003 / MRC_ / Medical Research Council / United Kingdom MRC_MC_UU_12012/1 / MRC_ / Medical Research Council / United Kingdom G19/35 / MRC_ / Medical Research Council / United Kingdom T32 GM080178 / GM / NIGMS NIH HHS / United States U01 AG009740 / AG / NIA NIH HHS / United States G0100222 / MRC_ / Medical Research Council / United Kingdom MRC_MC_UU_12015/1 / MRC_ / Medical Research Council / United Kingdom U01 HG007416 / HG / NHGRI NIH HHS / United States MRC_G1001799 / MRC_ / Medical Research Council / United Kingdom WT084766 / WT_ / Wellcome Trust / United Kingdom RG/08/014/24067 / BHF_ / British Heart Foundation / United Kingdom MRC_G9521010 / MRC_ / Medical Research Council / United Kingdom R01 DK072193 / DK / NIDDK NIH HHS / United States MRC_G0401527 / MRC_ / Medical Research Council / United Kingdom MRC_MC_UU_12015/5 / MRC_ / Medical Research Council / United Kingdom MC_UU_12019/1 / MRC_ / Medical Research Council / United Kingdom G8802774 / MRC_ / Medical Research Council / United Kingdom P30 DK056341 / DK / NIDDK NIH HHS / United States G1000143 / MRC_ / Medical Research Council / United Kingdom U01 HG007376 / HG / NHGRI NIH HHS / United States WT098381 / WT_ / Wellcome Trust / United Kingdom G0902037 / MRC_ / Medical Research Council / United Kingdom U01 CA164930 / CA / NCI NIH HHS / United States R01 DK075787 / DK / NIDDK NIH HHS / United States UL1 TR000124 / TR / NCATS NIH HHS / United States MR/L003120/1 / MRC_ / Medical Research Council / United Kingdom R01 AG025941 / AG / NIA NIH HHS / United States CSO_CZB/4/672 / CSO_ / Chief Scientist Office / United Kingdom R01 AG041517 / AG / NIA NIH HHS / United States MRC_MC_PC_U127561128 / MRC_ / Medical Research Council / United Kingdom MC_UU_12015/1 / MRC_ / Medical Research Council / United Kingdom MRC_MC_UU_12015/2 / MRC_ / Medical Research Council / United Kingdom R01 DK062370 / DK / NIDDK NIH HHS / United States R01 HL105756 / HL / NHLBI NIH HHS / United States MC_U106179471 / MRC_ / Medical Research Council / United Kingdom MR/N01104X/1 / MRC_ / Medical Research Council / United Kingdom R25 GM062459 / GM / NIGMS NIH HHS / United States CSO_CZB/4/710 / CSO_ / Chief Scientist Office / United Kingdom P30 DK063491 / DK / NIDDK NIH HHS / United States 097117 / WT_ / Wellcome Trust / United Kingdom MC_UU_12015/2 / MRC_ / Medical Research Council / United Kingdom WT098017 / WT_ / Wellcome Trust / 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 / CRUK_ / Cancer Research UK / United Kingdom R01 AG033193 / AG / NIA NIH HHS / United States G1000616 / MRC_ / Medical Research Council / United Kingdom MRC_MC_UP_A100_1003 / MRC_ / Medical Research Council / United Kingdom MC_U106179472 / MRC_ / Medical Research Council / United Kingdom G0401527 / MRC_ / Medical Research Council / United Kingdom MRC_G0601261 / MRC_ / Medical Research Council / United Kingdom MC_UU_12013/1 / MRC_ / Medical Research Council / United Kingdom BHF_RG/08/008/25291 / BHF_ / British Heart Foundation / United Kingdom P30 DK020541 / DK / NIDDK NIH HHS / United States MC_PC_U127561128 / MRC_ / Medical Research Council / United Kingdom UM1 CA182913 / CA / NCI NIH HHS / United States U01 DK062370 / DK / NIDDK NIH HHS / United States G0600717 / MRC_ / Medical Research Council / United Kingdom WT100574 / WT_ / Wellcome Trust / United Kingdom P30 HL107251 / HL / NHLBI NIH HHS / United States MRC_MC_UU_12013/1 / MRC_ / Medical Research Council / United Kingdom 084766 / WT_ / Wellcome Trust / United Kingdom MRC_MR/N01104X/1 / MRC_ / Medical Research Council / United Kingdom 100574 / WT_ / Wellcome Trust / United Kingdom MRC_MC_U106179472 / MRC_ / Medical Research Council / United Kingdom FS/14/55/30806 / BHF_ / British Heart Foundation / United Kingdom P30 GM103341 / GM / NIGMS NIH HHS / United States R01 DK089256 / DK / NIDDK NIH HHS / United States MR/K006584/1 / MRC_ / Medical Research Council / United Kingdom MR/K013351/1 / MRC_ / Medical Research Council / United Kingdom BHF_FS/14/55/30806 / BHF_ / British Heart Foundation / United Kingdom MRC_MC_U106179471 / MRC_ / Medical Research Council / United Kingdom CRUK_14136 / CRUK_ / Cancer Research UK / United Kingdom P30 DK020572 / DK / NIDDK NIH HHS / United States MC_UU_12015/5 / MRC_ / Medical Research Council / United Kingdom MRC_MR/K013351/1 / MRC_ / Medical Research Council / United Kingdom P60 DK020541 / DK / NIDDK NIH HHS / United States P30 AG010129 / AG / NIA NIH HHS / United States R01 HL117626 / HL / NHLBI NIH HHS / United States 098381 / WT_ / Wellcome Trust / United Kingdom R01 HL117078 / HL / NHLBI NIH HHS / United States WT085235 / WT_ / Wellcome Trust / United Kingdom MRC_G1000143 / MRC_ / Medical Research Council / United Kingdom T32 HL007055 / HL / NHLBI NIH HHS / United States MRC_MR/L003120/1 / MRC_ / Medical Research Council / United Kingdom G0601261 / MRC_ / Medical Research Council / United Kingdom UM1 CA182910 / CA / NCI NIH HHS / United States P2C HD050924 / HD / NICHD NIH HHS / United States R01 DK078150 / DK / NIDDK NIH HHS / United States MRC_MC_UU_12019/1 / MRC_ / Medical Research Council / United Kingdom BHF_RG/10/12/28456 / BHF_ / British Heart Foundation / United Kingdom UL1 TR001067 / TR / NCATS NIH HHS / United States MRC_MR/K006584/1 / MRC_ / Medical Research Council / United Kingdom U01 AG049505 / AG / NIA NIH HHS / United States RG/07/008/23674 / BHF_ / British Heart Foundation / United Kingdom RG/10/12/28456 / BHF_ / British Heart Foundation / United Kingdom |