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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

Ji, Yingjie; Yiorkas, Andrianos M.; Frau, Francesca; Mook-Kanamori, Dennis; Staiger, Harald; Thomas, E. Louise; Atabaki-Pasdar, Naeimeh LU ; Campbell, Archie; Tyrrell, Jessica and Jones, Samuel E., et al. (2019) In Diabetes 68(1). p.207-219
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... (More)

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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@article{2408569c-f6a8-4008-be4d-2bb61336b6d5,
  abstract     = {<p>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.</p>},
  author       = {Ji, Yingjie and Yiorkas, Andrianos M. and Frau, Francesca and Mook-Kanamori, Dennis and Staiger, Harald and Thomas, E. Louise and Atabaki-Pasdar, Naeimeh and Campbell, Archie and Tyrrell, Jessica and Jones, Samuel E. and Beaumont, Robin N. and Wood, Andrew R. and Tuke, Marcus A. and Ruth, Katherine S. and Mahajan, Anubha and Murray, Anna and Freathy, Rachel M. and Weedon, Michael N. and Hattersley, Andrew T. and Hayward, Caroline and Machann, Jürgen and Häring, Hans Ulrich and Franks, Paul and de Mutsert, Renée and Pearson, Ewan and Stefan, Norbert and Frayling, Timothy M. and Allebrandt, Karla V. and Bell, Jimmy D. and Blakemore, Alexandra I. and Yaghootkar, Hanieh},
  issn         = {0012-1797},
  language     = {eng},
  number       = {1},
  pages        = {207--219},
  publisher    = {American Diabetes Association Inc.},
  series       = {Diabetes},
  title        = {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},
  url          = {http://dx.doi.org/10.2337/db18-0708},
  volume       = {68},
  year         = {2019},
}