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, et al. |
Secondary Authors | 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 | 1476-4687 |
Keywords | Adipogenesis, Adiposity, Age Factors, Body Mass Index, Continental Population Groups, Energy Metabolism, Europe, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Glutamic Acid, Humans, Insulin, Insulin Secretion, 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 (PĀ 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 |
Alternate Journal | Nature |
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 |