Genetic studies of body mass index yield new insights for obesity biology.
Nature
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| 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. |
| Year of Publication | 2015
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| Journal | Nature
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| Volume | 518
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| Issue | 7538
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| Pages | 197-206
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| Date Published | 2015 Feb 12
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| ISSN | 1476-4687
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| URL | |
| DOI | 10.1038/nature14177
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| PubMed ID | 25673413
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| PubMed Central ID | PMC4382211
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| 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
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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
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