TY - JOUR
T1 - 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
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
N1 - Publisher Copyright:
© 2018 by the American Diabetes Association.
PY - 2019/1/1
Y1 - 2019/1/1
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 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.
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 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.
UR - http://www.scopus.com/inward/record.url?scp=85058904141&partnerID=8YFLogxK
U2 - 10.2337/db18-0708
DO - 10.2337/db18-0708
M3 - Article
C2 - 30352878
AN - SCOPUS:85058904141
SN - 0012-1797
VL - 68
SP - 207
EP - 219
JO - Diabetes
JF - Diabetes
IS - 1
ER -
