A genome-wide search for type 2 diabetes susceptibility genes in an extended Arab family.
作者： Habiba S. Al Safar , Heather J. Cordell , Osman Jafer , Denise Anderson , Sarra E. Jamieson
DOI: 10.1111/AHG.12036
关键词:
摘要: Summary Twenty percent of people aged 20 to 79 have type 2 diabetes (T2D) in the United Arab Emirates (UAE). Genome-wide association studies (GWAS) identify genes for T2D not been reported countries. We performed a discovery GWAS an extended UAE family (N = 178; 66 diabetic; 112 healthy) genotyped on Illumina Human 660 Quad Beadchip, with independent replication top hits 116 cases and 199 controls. Power achieve genome-wide significance (commonly P 5 × 10−8) was therefore limited. Nevertheless, transmission disequilibrium testing FBAT identified at Chromosome 4p12-p13 (KCTD8: rs4407541, 9.70 10−6; GABRB1: rs10517178/rs1372491, 4.19 10−6) 14q13 (PRKD1: rs10144903, 3.92 10−6), supported by analysis using linear mixed model approximation GenABEL (4p12-p13 GABRG1/GABRA2: rs7662743, Padj-agesex 2.06 10−5; KCTD8: 1.42 10−4; 0.027; PRKD1: 6.95 10−5). SNPs across GABRG1/GABRA2 did replicate, whereas more proximal rs7679715 (Padj-agesex 0.030) rs2055942 0.022) COX7B2/GABRA4 did, addition trend distally KCTD8 (rs4695718: 0.096). Modelling data support signals GABRA4 (rs2055942: Padj-agesex-combined 3 10−4) 10−4). Replication observed PRKD1 rs1953722 (proxy rs10144903; 0.031; These may provide important functional leads understanding disease pathogenesis this population.
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