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

Published

Journal Article

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.

Full Text

Duke Authors

Cited 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; Mägi, R; Randall, JC; Winkler, TW; Wood, AR; Workalemahu, T; Faul, JD; Smith, JA; Zhao, JH; 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, 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, IM; Medina-Gomez, C; Medland, SE; Nalls, MA; Palmer, CD; Pasko, D; Pechlivanis, S; Peters, MJ; Prokopenko, I; Shungin, D; StanĨáková, A; Strawbridge, RJ; Sung, YJ; 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; Clarke, R; Daw, EW; 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; Lind, L; 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, NR; Rose, LM; Sanna, S; Scharnagl, H; Scholtens, S; Schumacher, FR; Scott, WR; Seufferlein, T; Shi, J; Smith, AV; Smolonska, J; Stanton, AV; Steinthorsdottir, V; Stirrups, K; 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, D; Weedon, MN; Wilkens, LR; Willenborg, C; Wilsgaard, T; Wojczynski, MK; Wong, A; Wright, AF; Zhang, Q; LifeLines Cohort Study, ; 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; van 't Hooft, FM; Vinkhuyzen, AAE; Westra, H-J; Zheng, W; Zondervan, KT; 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, ; 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; Cupples, LA; Cusi, D; Danesh, J; de Faire, U; den 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; Hovingh, GK; Humphries, SE; Hunt, SC; Hyppönen, E; Illig, T; Jacobs, KB; Jarvelin, M-R; Jöckel, K-H; Johansen, B; Jousilahti, P; Jukema, JW; 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; Marchand, LL; 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; Zillikens, MC; 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, PE; 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, GR; Franke, L; 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, JN; Loos, RJF; Speliotes, EK

Published Date

  • February 12, 2015

Published In

Volume / Issue

  • 518 / 7538

Start / End Page

  • 197 - 206

PubMed ID

  • 25673413

Pubmed Central ID

  • 25673413

Electronic International Standard Serial Number (EISSN)

  • 1476-4687

Digital Object Identifier (DOI)

  • 10.1038/nature14177

Language

  • eng

Conference Location

  • England