| Autor: |
Barbitoff YA; Biobank of the Research Park, Saint Petersburg State University, 199034 Saint Petersburg, Russia. barbitoff@bioinf.me.; Bioinformatics Institute, 194100 Saint Petersburg, Russia. barbitoff@bioinf.me.; Department of Genetics and Biotechnology, Saint Petersburg State University, 199034 Saint Petersburg, Russia. barbitoff@bioinf.me.; Institute of Translation Biomedicine, Saint Petersburg State University, 199034 Saint Petersburg, Russia. barbitoff@bioinf.me., Serebryakova EA; Biobank of the Research Park, Saint Petersburg State University, 199034 Saint Petersburg, Russia. e.a.zhukova@spbu.ru.; Laboratory of Prenatal Diagnostics of Hereditary Diseases, FSBSI «The Research Institute of Obstetrics, Gynaecology and Reproductology Named after D.O. Ott», 199034 Saint Petersburg, Russia. e.a.zhukova@spbu.ru.; City Hospital No. 40, Sestroretsk, 197706 Saint Petersburg, Russia. e.a.zhukova@spbu.ru., Nasykhova YA; Biobank of the Research Park, Saint Petersburg State University, 199034 Saint Petersburg, Russia. yulnasa@gmail.com.; Laboratory of Prenatal Diagnostics of Hereditary Diseases, FSBSI «The Research Institute of Obstetrics, Gynaecology and Reproductology Named after D.O. Ott», 199034 Saint Petersburg, Russia. yulnasa@gmail.com., Predeus AV; Bioinformatics Institute, 194100 Saint Petersburg, Russia. predeus@bioinf.me., Polev DE; Biobank of the Research Park, Saint Petersburg State University, 199034 Saint Petersburg, Russia. dmitrii.polev@spbu.ru., Shuvalova AR; Biobank of the Research Park, Saint Petersburg State University, 199034 Saint Petersburg, Russia. shuvalova_anna_radionovna@mail.ru., Vasiliev EV; City Hospital No. 40, Sestroretsk, 197706 Saint Petersburg, Russia. Vasilievev@mail.ru., Urazov SP; City Hospital No. 40, Sestroretsk, 197706 Saint Petersburg, Russia. urasta@list.ru., Sarana AM; Institute of Translation Biomedicine, Saint Petersburg State University, 199034 Saint Petersburg, Russia. asarana@mail.ru.; City Hospital No. 40, Sestroretsk, 197706 Saint Petersburg, Russia. asarana@mail.ru., Scherbak SG; Institute of Translation Biomedicine, Saint Petersburg State University, 199034 Saint Petersburg, Russia. sgsherbak@mail.ru.; City Hospital No. 40, Sestroretsk, 197706 Saint Petersburg, Russia. sgsherbak@mail.ru., Gladyshev DV; City Hospital No. 40, Sestroretsk, 197706 Saint Petersburg, Russia. gladyshev@gmail.com., Pokrovskaya MS; Federal State Institution «National Medical Research Center for Preventive Medicine» of the Ministry of Healthcare of the Russian Federation, 101990 Moscow, Russia. mpokrovskaya@gnicpm.ru., Sivakova OV; Federal State Institution «National Medical Research Center for Preventive Medicine» of the Ministry of Healthcare of the Russian Federation, 101990 Moscow, Russia. osivakova@gnicpm.ru., Meshkov AN; Federal State Institution «National Medical Research Center for Preventive Medicine» of the Ministry of Healthcare of the Russian Federation, 101990 Moscow, Russia. meshkov@lipidclinic.ru., Drapkina OM; Federal State Institution «National Medical Research Center for Preventive Medicine» of the Ministry of Healthcare of the Russian Federation, 101990 Moscow, Russia. odrapkina@gnicpm.ru., Glotov OS; Laboratory of Prenatal Diagnostics of Hereditary Diseases, FSBSI «The Research Institute of Obstetrics, Gynaecology and Reproductology Named after D.O. Ott», 199034 Saint Petersburg, Russia. olglotov@mai.ru.; City Hospital No. 40, Sestroretsk, 197706 Saint Petersburg, Russia. olglotov@mai.ru., Glotov AS; Biobank of the Research Park, Saint Petersburg State University, 199034 Saint Petersburg, Russia. a.glotov@spbu.ru.; Laboratory of Prenatal Diagnostics of Hereditary Diseases, FSBSI «The Research Institute of Obstetrics, Gynaecology and Reproductology Named after D.O. Ott», 199034 Saint Petersburg, Russia. a.glotov@spbu.ru. |
| Abstrakt: |
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. |
