Genome-wide and abdominal MRI data provide evidence that a genetically determined favorable adiposity phenotype is characterized by lower ectopic liver fat and lower risk of type 2 diabetes, heart disease, and hypertension

Research output: Contribution to journalArticle

Abstract

Recent genetic studies have identified alleles associated with opposite effects on adiposity and risk of type 2 diabetes. We aimed to identify more of these variants and test the hypothesis that such favorable adiposity alleles are associated with higher subcutaneous fat and lower ectopic fat. We combined MRI data with genome-wide association studies of body fat percentage (%) and metabolic traits. We report 14 alleles, including 7 newly characterized alleles, associated with higher adiposity but a favorable metabolic profile. Consistent with previous studies, individuals carrying more favorable adiposity alleles had higher body fat % and higher BMI but lower risk of type 2 diabetes, heart disease, and hypertension. These individuals also had higher subcutaneous fat but lower liver fat and a lower visceral-to-subcutaneous adipose tissue ratio. Individual alleles associated with higher body fat % but lower liver fat and lower risk of type 2 diabetes included those in PPARG, GRB14, and IRS1, whereas the allele in ANKRD55 was paradoxically associated with higher visceral fat but lower risk of type 2 diabetes. Most identified favorable adiposity alleles are associated with higher subcutaneous and lower liver fat, a mechanism consistent with the beneficial effects of storing excess triglycerides in metabolically low-risk depots.

Details

Authors
  • Yingjie Ji
  • Andrianos M. Yiorkas
  • Francesca Frau
  • Dennis Mook-Kanamori
  • Harald Staiger
  • E. Louise Thomas
  • Archie Campbell
  • Jessica Tyrrell
  • Samuel E. Jones
  • Robin N. Beaumont
  • Andrew R. Wood
  • Marcus A. Tuke
  • Katherine S. Ruth
  • Anubha Mahajan
  • Anna Murray
  • Rachel M. Freathy
  • Michael N. Weedon
  • Andrew T. Hattersley
  • Caroline Hayward
  • Jürgen Machann
  • Hans Ulrich Häring
  • Renée de Mutsert
  • Ewan Pearson
  • Norbert Stefan
  • Timothy M. Frayling
  • Karla V. Allebrandt
  • Jimmy D. Bell
  • Alexandra I. Blakemore
  • Hanieh Yaghootkar
Organisations
External organisations
  • University of Exeter
  • Imperial College London
  • Brunel University London
  • Leiden University Medical Centre
  • University of Tübingen
  • University of Westminster
  • Skåne University Hospital
  • University of Edinburgh
  • Wellcome Trust Centre for Human Genetics
  • Umeå University
  • Harvard University
  • Ninewells Hospital and Medical School
  • Royal Devon & Exeter Hospital
  • Sanofi-Aventis Deutschland GmbH
  • German Center for Diabetes Research
  • University of Dundee
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Medical Genetics
  • Endocrinology and Diabetes
Original languageEnglish
Pages (from-to)207-219
Number of pages13
JournalDiabetes
Volume68
Issue number1
Publication statusPublished - 2019
Publication categoryResearch
Peer-reviewedYes