TY - JOUR
T1 - Genome-Wide and Abdominal MRI-Imaging Data Provides Evidence that a Genetically Determined Favourable Adiposity Phenotype is Characterized by Lower Ectopic Liver Fat and Lower Risk of Type 2 Diabetes, Heart Disease and Hypertension
AU - Ji, Yingjie
AU - Yiorkas, Andrianos M.
AU - Frau, Francesca
AU - Mook-kanamori, Dennis
AU - Staiger, Harald
AU - Thomas, E. Louise
AU - Atabaki-pasdar, Naeimeh
AU - Campbell, Archie
AU - Tyrrell, Jessica
AU - Jones, Samuel E.
AU - Beaumont, Robin N.
AU - Wood, Andrew R.
AU - Tuke, Marcus A.
AU - Ruth, Katherine S.
AU - Mahajan, Anubha
AU - Murray, Anna
AU - Freathy, Rachel M.
AU - Weedon, Michael N.
AU - Hattersley, Andrew T.
AU - Hayward, Caroline
AU - Machann, Jürgen
AU - Häring, Hans-ulrich
AU - Franks, Paul
AU - De Mutsert, Renée
AU - Pearson, Ewan
AU - Stefan, Norbert
AU - Frayling, Timothy M.
AU - Allebrandt, Karla V.
AU - Bell, Jimmy D.
AU - Blakemore, Alexandra I.
AU - Yaghootkar, Hanieh
PY - 2018/10/23
Y1 - 2018/10/23
N2 - 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 “favourable adiposity” alleles are associated with higher subcutaneous fat and lower ectopic fat. We combined magnetic resonance imaging (MRI) data with genome-wide association studies (GWAS) of body fat % and metabolic traits. We report 14 alleles, including 7 newly characterized alleles, associated with higher adiposity, but a favourable metabolic profile. Consistent with previous studies, individuals carrying more “favourable 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 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, whilst the allele in ANKRD55 was paradoxically associated with higher visceral fat but lower risk of type 2 diabetes. Most identified “favourable adiposity” alleles are associated with higher subcutaneous and lower liver fat, a mechanism consistent with the beneficial effects of storing excess triglyceride in metabolically low risk depots.
AB - 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 “favourable adiposity” alleles are associated with higher subcutaneous fat and lower ectopic fat. We combined magnetic resonance imaging (MRI) data with genome-wide association studies (GWAS) of body fat % and metabolic traits. We report 14 alleles, including 7 newly characterized alleles, associated with higher adiposity, but a favourable metabolic profile. Consistent with previous studies, individuals carrying more “favourable 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 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, whilst the allele in ANKRD55 was paradoxically associated with higher visceral fat but lower risk of type 2 diabetes. Most identified “favourable adiposity” alleles are associated with higher subcutaneous and lower liver fat, a mechanism consistent with the beneficial effects of storing excess triglyceride in metabolically low risk depots.
U2 - 10.2337/db18-0708
DO - 10.2337/db18-0708
M3 - Article
SN - 0012-1797
SP - db180708
JO - Diabetes
JF - Diabetes
ER -