Large meta-analysis of genome-wide association studies identifies five loci for lean body mass.

Nat Commun
Authors
Keywords
Abstract

Lean body mass, consisting mostly of skeletal muscle, is important for healthy aging. We performed a genome-wide association study for whole body (20 cohorts of European ancestry with n = 38,292) and appendicular (arms and legs) lean body mass (n = 28,330) measured using dual energy X-ray absorptiometry or bioelectrical impedance analysis, adjusted for sex, age, height, and fat mass. Twenty-one single-nucleotide polymorphisms were significantly associated with lean body mass either genome wide (p  5 × 10) or suggestively genome wide (p  2.3 × 10). Replication in 63,475 (47,227 of European ancestry) individuals from 33 cohorts for whole body lean body mass and in 45,090 (42,360 of European ancestry) subjects from 25 cohorts for appendicular lean body mass was successful for five single-nucleotide polymorphisms in/near HSD17B11, VCAN, ADAMTSL3, IRS1, and FTO for total lean body mass and for three single-nucleotide polymorphisms in/near VCAN, ADAMTSL3, and IRS1 for appendicular lean body mass. Our findings provide new insight into the genetics of lean body mass.Lean body mass is a highly heritable trait and is associated with various health conditions. Here, Kiel and colleagues perform a meta-analysis of genome-wide association studies for whole body lean body mass and find five novel genetic loci to be significantly associated.

Year of Publication
2017
Journal
Nat Commun
Volume
8
Issue
1
Pages
80
Date Published
2017 07 19
ISSN
2041-1723
DOI
10.1038/s41467-017-00031-7
PubMed ID
28724990
PubMed Central ID
PMC5517526
Links
Grant list
UL1 RR033176 / RR / NCRR NIH HHS / United States
F31 AA025278 / AA / NIAAA NIH HHS / United States
R01 HL103612 / HL / NHLBI NIH HHS / United States
R00 DK099240 / DK / NIDDK NIH HHS / United States
P60 AR049465 / AR / NIAMS NIH HHS / United States
R01 AR046838 / AR / NIAMS NIH HHS / United States
N01AG12100 / AG / NIA NIH HHS / United States
R01 AG024480 / AG / NIA NIH HHS / United States
R01 HL120393 / HL / NHLBI NIH HHS / United States
P30 DK048520 / DK / NIDDK NIH HHS / United States
R01 AG015928 / AG / NIA NIH HHS / United States
N01 AG062101 / AG / NIA NIH HHS / United States
U01 HL080295 / HL / NHLBI NIH HHS / United States
P60 AR030701 / AR / NIAMS NIH HHS / United States
UL1 TR000128 / TR / NCATS NIH HHS / United States
R01 AR035583 / AR / NIAMS NIH HHS / United States
U01 HL130114 / HL / NHLBI NIH HHS / United States
UL1 TR002369 / TR / NCATS NIH HHS / United States
N01 HC015103 / HC / NHLBI NIH HHS / United States
U01 HL120393 / HL / NHLBI NIH HHS / United States
ZIA HG000024 / HG / NHGRI NIH HHS / United States
R01 AR035584 / AR / NIAMS NIH HHS / United States
R56 AG020098 / AG / NIA NIH HHS / United States
N01 HC085085 / HC / NHLBI NIH HHS / United States
G1000143 / Medical Research Council / United Kingdom
U01 AG042124 / AG / NIA NIH HHS / United States
R01 AG017917 / AG / NIA NIH HHS / United States
R01 HL087652 / HL / NHLBI NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
N01 AG062106 / AG / NIA NIH HHS / United States
N01HC55222 / HL / NHLBI NIH HHS / United States
U01 AG042145 / AG / NIA NIH HHS / United States
R01 AG027576 / AG / NIA NIH HHS / United States
R01 DK075681 / DK / NIDDK NIH HHS / United States
R01 AR041398 / AR / NIAMS NIH HHS / United States
R01 AG041517 / AG / NIA NIH HHS / United States
N01HC85086 / HL / NHLBI NIH HHS / United States
MC_UU_12015/1 / Medical Research Council / United Kingdom
R01 HL105756 / HL / NHLBI NIH HHS / United States
M01 RR000750 / RR / NCRR NIH HHS / United States
R01 AG032098 / AG / NIA NIH HHS / United States
U01 HL084756 / HL / NHLBI NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
HHSN268200782096C / HG / NHGRI NIH HHS / United States
S10 OD016290 / OD / NIH HHS / United States
R01 AG005407 / AG / NIA NIH HHS / United States
HHSN268201200036C / HL / NHLBI NIH HHS / United States
P30 DK072488 / DK / NIDDK NIH HHS / United States
14136 / Cancer Research UK / United Kingdom
N01 AG062103 / AG / NIA NIH HHS / United States
U01 AG042168 / AG / NIA NIH HHS / United States
G0401527 / Medical Research Council / United Kingdom
P30 DK020541 / DK / NIDDK NIH HHS / United States
U01 AG042140 / AG / NIA NIH HHS / United States
U01 HL072515 / HL / NHLBI NIH HHS / United States
R01 HL080295 / HL / NHLBI NIH HHS / United States
U24 AG051129 / AG / NIA NIH HHS / United States
U01 DK062370 / DK / NIDDK NIH HHS / United States
R01 AR057118 / AR / NIAMS NIH HHS / United States
R01 HL088215 / HL / NHLBI NIH HHS / United States
N01 HC085084 / HC / NHLBI NIH HHS / United States
R01 AG020098 / AG / NIA NIH HHS / United States
N01HC85082 / HL / NHLBI NIH HHS / United States
N01HC75150 / HL / NHLBI NIH HHS / United States
R01 DK089256 / DK / NIDDK NIH HHS / United States
N01HC85083 / HL / NHLBI NIH HHS / United States
N01HC25195 / HL / NHLBI NIH HHS / United States
P30 DK020572 / DK / NIDDK NIH HHS / United States
RC2 AR058973 / AR / NIAMS NIH HHS / United States
R01 AR035582 / AR / NIAMS NIH HHS / United States
Wellcome Trust / United Kingdom
U01 AG027810 / AG / NIA NIH HHS / United States
R01 AG005394 / AG / NIA NIH HHS / United States
F32 AR059469 / AR / NIAMS NIH HHS / United States
R01 HL117078 / HL / NHLBI NIH HHS / United States
R01 AG023629 / AG / NIA NIH HHS / United States
R01 AG027058 / AG / NIA NIH HHS / United States
N01 HC045133 / HC / NHLBI NIH HHS / United States
R01 HL087700 / HL / NHLBI NIH HHS / United States
N01HC85080 / HL / NHLBI NIH HHS / United States
U01 GM074518 / GM / NIGMS NIH HHS / United States
N01 HC035129 / HC / NHLBI NIH HHS / United States
R56 AG023629 / AG / NIA NIH HHS / United States
U01 AG042143 / AG / NIA NIH HHS / United States
N01WH22110 / WH / WHI NIH HHS / United States
U01 AG042139 / AG / NIA NIH HHS / United States
R01 AG027574 / AG / NIA NIH HHS / United States
R01 AG015819 / AG / NIA NIH HHS / United States
U01 AR066160 / AR / NIAMS NIH HHS / United States
N01HC85081 / HL / NHLBI NIH HHS / United States
R01 HL088119 / HL / NHLBI NIH HHS / United States
N01HC85079 / HL / NHLBI NIH HHS / United States
WT098051 / Wellcome Trust / United Kingdom
CIHR / Canada
SP/04/002 / British Heart Foundation / United Kingdom
CZB/4/276 / Chief Scientist Office / United Kingdom
CZB/4/710 / Chief Scientist Office / United Kingdom
WT098017 / Wellcome Trust / United Kingdom