Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Royal Devon and Exeter Hospital, Exeter, U.K.
Section of Investigative Medicine, Imperial College London, London, U.K.
Diabetes. 2019 Jan;68(1):207-219. doi: 10.2337/db18-0708. Epub 2018 Oct 23.
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 , , and , whereas the allele in 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.
最近的遗传学研究已经确定了与肥胖和 2 型糖尿病风险呈相反作用的等位基因。我们旨在鉴定更多的这些变体，并验证这样的有利肥胖等位基因与更高的皮下脂肪和更低的异位脂肪有关的假设。我们将 MRI 数据与全身脂肪百分比（%）和代谢特征的全基因组关联研究相结合。我们报告了 14 个等位基因，包括 7 个新鉴定的等位基因，它们与更高的肥胖程度但有利的代谢特征相关。与先前的研究一致，携带更多有利肥胖等位基因的个体具有更高的体脂肪%和更高的 BMI，但患 2 型糖尿病、心脏病和高血压的风险较低。这些个体还具有更高的皮下脂肪，但更低的肝脂肪和更低的内脏-皮下脂肪组织比。与更高的体脂肪%但更低的肝脂肪和更低的 2 型糖尿病风险相关的个体等位基因包括那些位于 、 、 和 ，而位于 中的等位基因则与更高的内脏脂肪但更低的 2 型糖尿病风险相关。大多数鉴定出的有利肥胖等位基因与更高的皮下脂肪和更低的肝脂肪有关，这一机制与将多余的甘油三酯储存在代谢风险较低的部位的有益作用一致。
