Identification of Novel Candidate Markers of Type 2 Diabetes and Obesity in Russia by Exome Sequencing with a Limited Sample Size.

Type 2 diabetes (T2D) and obesity are common chronic disorders with multifactorial etiology. In our study, we performed an exome sequencing analysis of 110 patients of Russian ethnicity together with a multi-perspective approach based on biologically meaningful filtering criteria to detect novel candidate variants and loci for T2D and obesity. We have identified several known single nucleotide polymorphisms (SNPs) as markers for obesity (rs11960429), T2D (rs9379084, rs1126930), and body mass index (BMI) (rs11553746, rs1956549 and rs7195386) ( < 0.05). We show that a method based on scoring of case-specific variants together with selection of protein-altering variants can allow for the interrogation of novel and known candidate markers of T2D and obesity in small samples. Using this method, we identified rs328 in ( = 0.023), rs11863726 in ( = 8 × 10), rs112984085 in ( = 4.8 × 10) for T2D and obesity, rs6271 in ( = 0.043), rs62618693 in ( = 0.021), rs61758785 in ( = 1.7 × 10), rs34042554 in ( = 1 × 10), and rs144183813 in ( = 1.7 × 10) for obesity; and rs9379084 in ( = 0.042), rs2233984 in ( = 0.030), rs61737764 in ( = 0.035), rs17801742 in ( = 8.5 × 10), and rs685523 in ( = 1 × 10) for T2D as important susceptibility loci in Russian population. Our results demonstrate the effectiveness of whole exome sequencing (WES) technologies for searching for novel markers of multifactorial diseases in cohorts of limited size in poorly studied populations.