Inherited basis of visceral, abdominal subcutaneous and gluteofemoral fat depots

Saaket Agrawal, Minxian Wang, Marcus D. R. Klarqvist, Kirk Smith, Joseph Shin, Hesam Dashti, Nathaniel Diamant, Seung Hoan Choi, Sean J. Jurgens, Patrick T. Ellinor, Anthony Philippakis, Melina Claussnitzer, Kenney Ng, Miriam S. Udler, Puneet Batra and Amit V. Khera ()
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Saaket Agrawal: Broad Institute of MIT and Harvard
Minxian Wang: Broad Institute of MIT and Harvard
Marcus D. R. Klarqvist: Broad Institute of MIT and Harvard
Kirk Smith: Broad Institute of MIT and Harvard
Joseph Shin: Broad Institute of MIT and Harvard
Hesam Dashti: Broad Institute of MIT and Harvard
Nathaniel Diamant: Broad Institute of MIT and Harvard
Seung Hoan Choi: Broad Institute of MIT and Harvard
Sean J. Jurgens: Broad Institute of MIT and Harvard
Patrick T. Ellinor: Broad Institute of MIT and Harvard
Anthony Philippakis: Broad Institute of MIT and Harvard
Melina Claussnitzer: Broad Institute of MIT and Harvard
Kenney Ng: Center for Computational Health, IBM Research
Miriam S. Udler: Broad Institute of MIT and Harvard
Puneet Batra: Broad Institute of MIT and Harvard
Amit V. Khera: Broad Institute of MIT and Harvard

Nature Communications, 2022, vol. 13, issue 1, 1-17

Abstract: Abstract 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.

Date: 2022
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DOI: 10.1038/s41467-022-30931-2

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