TY - JOUR
T1 - Inherited basis of visceral, abdominal subcutaneous and gluteofemoral fat depots
AU - Agrawal, Saaket
AU - Wang, Minxian
AU - Klarqvist, Marcus D. R.
AU - Smith, Kirk
AU - Shin, Joseph
AU - Dashti, Hesam
AU - Diamant, Nathaniel
AU - Choi, Seung Hoan
AU - Jurgens, Sean J.
AU - Ellinor, Patrick T.
AU - Philippakis, Anthony
AU - Claussnitzer, Melina
AU - Ng, Kenney
AU - Udler, Miriam S.
AU - Batra, Puneet
AU - Khera, Amit V.
N1 - Funding Information: This work was supported by the Sarnoff Cardiovascular Research Foundation Fellowship (to S.A.), student scholarships from the Dutch Heart Foundation and the Amsterdams Studentenfonds (S.J.J.), grants 1K08HG010155 and 1U01HG011719 (to A.V.K.) from the National Human Genome Research Institute, a grant from the National Institute of Diabetes and Digestive and Kidney Diseases K23DK114551 (to M.S.U.), a Hassenfeld Scholar Award from Massachusetts General Hospital (to A.V.K.), a Merkin Institute Fellowship from the Broad Institute of MIT and Harvard (to A.V.K.), and a sponsored research agreement from IBM Research to the Broad Institute of MIT and Harvard (to P.T.E., A.P., P.B., and A.V.K.). Publisher Copyright: © 2022, The Author(s).
PY - 2022/12/1
Y1 - 2022/12/1
N2 - For any given level of overall adiposity, individuals vary considerably in fat distribution. The inherited basis of fat distribution in the general population is not fully understood. Here, we study up to 38,965 UK Biobank participants with MRI-derived visceral (VAT), abdominal subcutaneous (ASAT), and gluteofemoral (GFAT) adipose tissue volumes. Because these fat depot volumes are highly correlated with BMI, we additionally study six local adiposity traits: VAT adjusted for BMI and height (VATadj), ASATadj, GFATadj, VAT/ASAT, VAT/GFAT, and ASAT/GFAT. We identify 250 independent common variants (39 newly-identified) associated with at least one trait, with many associations more pronounced in female participants. Rare variant association studies extend prior evidence for PDE3B as an important modulator of fat distribution. Local adiposity traits (1) highlight depot-specific genetic architecture and (2) enable construction of depot-specific polygenic scores that have divergent associations with type 2 diabetes and coronary artery disease. These results – using MRI-derived, BMI-independent measures of local adiposity – confirm fat distribution as a highly heritable trait with important implications for cardiometabolic health outcomes.
AB - For any given level of overall adiposity, individuals vary considerably in fat distribution. The inherited basis of fat distribution in the general population is not fully understood. Here, we study up to 38,965 UK Biobank participants with MRI-derived visceral (VAT), abdominal subcutaneous (ASAT), and gluteofemoral (GFAT) adipose tissue volumes. Because these fat depot volumes are highly correlated with BMI, we additionally study six local adiposity traits: VAT adjusted for BMI and height (VATadj), ASATadj, GFATadj, VAT/ASAT, VAT/GFAT, and ASAT/GFAT. We identify 250 independent common variants (39 newly-identified) associated with at least one trait, with many associations more pronounced in female participants. Rare variant association studies extend prior evidence for PDE3B as an important modulator of fat distribution. Local adiposity traits (1) highlight depot-specific genetic architecture and (2) enable construction of depot-specific polygenic scores that have divergent associations with type 2 diabetes and coronary artery disease. These results – using MRI-derived, BMI-independent measures of local adiposity – confirm fat distribution as a highly heritable trait with important implications for cardiometabolic health outcomes.
UR - http://www.scopus.com/inward/record.url?scp=85133126223&partnerID=8YFLogxK
U2 - https://doi.org/10.1038/s41467-022-30931-2
DO - https://doi.org/10.1038/s41467-022-30931-2
M3 - Article
C2 - 35773277
SN - 2041-1723
VL - 13
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 3771
ER -