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

被引：24

作者：

Barbitoff, Yury A. ^{[1
,2
,3
,4
]}

Serebryakova, Elena A. ^{[1
,5
,6
]}

Nasykhova, Yulia A. ^{[1
,5
]}

Predeus, Alexander V. ^{[2
]}

Polev, Dmitrii E. ^{[1
]}

Shuvalova, Anna R. ^{[1
]}

Vasiliev, Evgenii V. ^{[6
]}

Urazov, Stanislav P. ^{[6
]}

Sarana, Andrey M. ^{[4
,6
]}

Scherbak, Sergey G. ^{[4
,6
]}

Gladyshev, Dmitrii V. ^{[6
]}

Pokrovskaya, Maria S. ^{[7
]}

Sivakova, Oksana V. ^{[7
]}

Meshkov, Aleksey N. ^{[7
]}

Drapkina, Oxana M. ^{[7
]}

Glotov, Oleg S. ^{[4
,5
,6
]}

Glotov, Andrey S. ^{[1
,4
,5
]}

机构：

[1] St Petersburg State Univ, Biobank Res Pk, St Petersburg 199034, Russia

[2] Bioinformat Inst, St Petersburg 194100, Russia

[3] St Petersburg State Univ, Dept Genet & Biotechnol, St Petersburg 199034, Russia

[4] St Petersburg State Univ, Inst Translat Biomed, St Petersburg 199034, Russia

[5] Res Inst Obstet Gynaecol & Reproductol, FSBSI, Lab Prenatal Diagnost Hereditary Dis, St Petersburg 199034, Russia

[6] City Hosp 4, St Petersburg 197706, Russia

[7] Minist Healthcare Russian Federat, Natl Med Res Ctr Prevent Med, Fed State Inst, Moscow 101990, Russia

来源：

GENES | 2018年 / 9卷 / 08期

基金：

俄罗斯科学基金会;

关键词：

type; 2; diabetes; obesity; next-generation sequencing; exome sequencing; susceptibility locus; single nucleotide polymorphisms; association study; ENDOTHELIAL DYSFUNCTION; ASSOCIATION; PROTEIN; DNA; POLYMORPHISMS; DISCOVERY; VARIANTS; GENETICS; MELLITUS; TRAITS;

D O I：

10.3390/genes9080415

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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 x 10(-5)), rs112984085 in VAV3 (p = 4.8 x 10(-4)) for T2D and obesity, rs6271 in DBH (p = 0.043), rs62618693 in QSER1 (p = 0.021), rs61758785 in RAD51B (p = 1.7 x 10(-4)), rs34042554 in PCDHA1 (p = 1 x 10(-4)), and rs144183813 in PLEKHA5 (p = 1.7 x 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 x 10(-5)), and rs685523 in ADAMTS13 (p = 1 x 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.

引用

页数：14

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