Abstract
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) (p < 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 LPL (p = 0.023), rs11863726 in HBQ1 (p = 8 × 10−5), rs112984085 in VAV3 (p = 4.8 × 10−4) for T2D and obesity, rs6271 in DBH (p = 0.043), rs62618693 in QSER1 (p = 0.021), rs61758785 in RAD51B (p = 1.7 × 10−4), rs34042554 in PCDHA1 (p = 1 × 10−4), and rs144183813 in PLEKHA5 (p = 1.7 × 10−4) for obesity; and rs9379084 in RREB1 (p = 0.042), rs2233984 in C6orf15 (p = 0.030), rs61737764 in ITGB6 (p = 0.035), rs17801742 in COL2A1 (p = 8.5 × 10−5), and rs685523 in ADAMTS13 (p = 1 × 10−6) 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.
Highlights
Type 2 diabetes (T2D) and obesity are common chronic disorders with multifactorial etiology.Due to their rising prevalence, they are recognized as a global epidemic by the World HealthOrganization (WHO) [1,2,3,4]
We identified rs689452 as the strongest associating single nucleotide polymorphisms (SNPs) (Table 2, Section 2)
Out of exome variants with intermediate frequency (0.02 < SPBU minor allele frequency (MAF) < 0.1) with high case-specificity score and statistical support, we found rs11863726 in HBQ1 and rs112984085 in VAV3 which were associated with T2D and obesity compared to controls, and rs685523 in ADAMTS13 as a specific marker for T2D
Summary
Type 2 diabetes (T2D) and obesity are common chronic disorders with multifactorial etiology.Due to their rising prevalence, they are recognized as a global epidemic by the World HealthOrganization (WHO) [1,2,3,4]. Type 2 diabetes (T2D) and obesity are common chronic disorders with multifactorial etiology. Due to their rising prevalence, they are recognized as a global epidemic by the World Health. Excessive weight and obesity are strongly correlated with T2D They can lead to adverse metabolic effects on blood pressure, cholesterol, triglycerides and insulin resistance. According to WHO, excessive weight and obesity account for 44% of diabetes cases [7,8]. Because of this close relationship, T2D and obesity can be considered as associated pathologies with a potential common genetic component
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
