Repository logo
 

Regional fat depot masses are influenced by protein-coding gene variants.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Wittemans, Laura BL 
Pinnick, Katherine E  ORCID logo  https://orcid.org/0000-0002-2422-248X
Todorčević, Marijana  ORCID logo  https://orcid.org/0000-0002-3100-8799
Kaksonen, Risto 

Abstract

Waist-to-hip ratio (WHR) is a prominent cardiometabolic risk factor that increases cardio-metabolic disease risk independently of BMI and for which multiple genetic loci have been identified. However, WHR is a relatively crude proxy for fat distribution and it does not capture all variation in fat distribution. We here present a study of the role of coding genetic variants on fat mass in 6 distinct regions of the body, based on dual-energy X-ray absorptiometry imaging on more than 17k participants. We find that the missense variant CCDC92S70C, previously associated with WHR, is associated specifically increased leg fat mass and reduced visceral but not subcutaneous central fat. The minor allele-carrying transcript of CCDC92 is constitutively more highly expressed in adipose tissue samples. In addition, we identify two coding variants in SPATA20 and UQCC1 that are associated with arm fat mass. SPATA20K422R is a low-frequency variant with a large effect on arm fat only, and UQCC1R51Q is a common variant reaching significance for arm but showing similar trends in other subcutaneous fat depots. Our findings support the notion that different fat compartments are regulated by distinct genetic factors.

Description

Keywords

Absorptiometry, Photon, Adipose Tissue, Adult, Body Composition, Body Fat Distribution, Body Mass Index, Cardiovascular Diseases, Humans, Male, Metabolic Diseases, Middle Aged, Obesity, Risk Factors, Subcutaneous Fat, Waist-Hip Ratio

Journal Title

PLoS One

Conference Name

Journal ISSN

1932-6203
1932-6203

Volume Title

14

Publisher

Public Library of Science (PLoS)
Sponsorship
Medical Research Council (MC_UU_12015/1)
Medical Research Council (MR/N003284/1)
Department of Health (via National Institute for Health Research (NIHR)) (NF-SI-0617-10149)
Medical Research Council (G1000143)
Medical Research Council (G0401527)
Medical Research Council (G0401527/1)
Cancer Research Uk (None)
Medical Research Council (MC_PC_13048)
Medical Research Council (MC_PC_13046)
Relationships
Is derived from: