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 | Zendy

Yingjie Ji | Zendy; Andrianos M. Yiorkas | Zendy; Francesca Frau | Zendy; Dennis O. MookKanamori | Zendy; Harald Staiger | Zendy; E. Louise Thomas | Zendy; Naeimeh AtabakiPasdar | Zendy; Archie Campbell | Zendy; Jessica Tyrrell | Zendy; Samuel E. Jones | Zendy; Robin N. Beaumont | Zendy; Andrew R. Wood | Zendy; Marcus A. Tuke | Zendy; Katherine S. Ruth | Zendy; Anubha Mahajan | Zendy; Anna Murray | Zendy; Rachel M. Freathy | Zendy; Michael N. Weedon | Zendy; Andrew T. Hattersley | Zendy; Caroline Hayward | Zendy; Jürgen Machann | Zendy; Hans-Ulrich Häring | Zendy; Paul W. Franks | Zendy; Renée de Mutsert | Zendy; Ewan R. Pearson | Zendy; Norbert Stefan | Zendy; Timothy M. Frayling | Zendy; Karla V. Allebrandt | Zendy; Jimmy D. Bell | Zendy; Alexandra I. F. Blakemore | Zendy; Hanieh Yaghootkar | Zendy

Open Access

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

Author(s) -

Yingjie Ji,

Andrianos M. Yiorkas,

Francesca Frau,

Dennis O. MookKanamori,

Harald Staiger,

E. Louise Thomas,

Naeimeh AtabakiPasdar,

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,

Paul W. Franks,

Renée de Mutsert,

Ewan R. Pearson,

Norbert Stefan,

Timothy M. Frayling,

Karla V. Allebrandt,

Jimmy D. Bell,

Alexandra I. F. Blakemore,

Hanieh Yaghootkar

Publication year - 2018

Publication title -

diabetes

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 3.219

H-Index - 330

eISSN - 1939-327X

pISSN - 0012-1797

DOI - 10.2337/db18-0708

Subject(s) - medicine , endocrinology , allele , type 2 diabetes , adipose tissue , diabetes mellitus , intra abdominal fat , steatosis , biology , insulin resistance , genetics , gene , visceral fat

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.

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