DESCRIPTION:

List of positional candidate genes after correcting for multiple testing and controlling the false discovery rate from genome wide association studies (GWAS) retrieved from the NHGRI-EBI Catalog of published genome-wide association studies (http://www.ebi.ac.uk/gwas/). The disease/trait examined in this study, as reported by the authors, was Type 2 diabetes. The EFO term type II diabetes mellitus was annotated to this set after curation by NHGRI-EBI. Intergenic SNPS were mapped to both the upstream and downstream gene. P-value uploaded. This gene set was generated using gwas2gs v. 0.1.8 and the GWAS Catalog v. 1.0.1.

LABEL:

GWAS: type II diabetes mellitus

SCORE TYPE:

P-Value

DATE ADDED:

2017-05-02

DATE UPDATED:

2024-04-25

SPECIES:

AUTHORS:

HS Al Safar, HJ Cordell, O Jafer, D Anderson, SE Jamieson, M Fakiola, K Khazanehdari, GK Tay, JM Blackwell

TITLE:

A genome-wide search for type 2 diabetes susceptibility genes in an extended Arab family.

JOURNAL:

Annals of human genetics Nov 2013, Vol 77, pp. 488-503

ABSTRACT:

Twenty percent of people aged 20 to 79 have type 2 diabetes (T2D) in the United Arab Emirates (UAE). Genome-wide association studies (GWAS) to identify genes for T2D have not been reported for Arab countries. We performed a discovery GWAS in an extended UAE family (N=178; 66 diabetic; 112 healthy) genotyped on the Illumina Human 660 Quad Beadchip, with independent replication of top hits in 116 cases and 199 controls. Power to achieve genome-wide significance (commonly P=5×10(-8)) was therefore limited. Nevertheless, transmission disequilibrium testing in FBAT identified top hits at Chromosome 4p12-p13 (KCTD8: rs4407541, P=9.70×10(-6); GABRB1: rs10517178/rs1372491, P=4.19×10(-6)) and 14q13 (PRKD1: rs10144903, 3.92×10(-6)), supported by analysis using a linear mixed model approximation in GenABEL (4p12-p13 GABRG1/GABRA2: rs7662743, Padj-agesex=2.06×10(-5); KCTD8: rs4407541, Padj-agesex=1.42×10(-4); GABRB1: rs10517178/rs1372491, Padj-agesex=0.027; 14q13 PRKD1: rs10144903, Padj-agesex=6.95×10(-5)). SNPs across GABRG1/GABRA2 did not replicate, whereas more proximal SNPs rs7679715 (Padj-agesex=0.030) and rs2055942 (Padj-agesex=0.022) at COX7B2/GABRA4 did, in addition to a trend distally at KCTD8 (rs4695718: Padj-agesex=0.096). Modelling of discovery and replication data support independent signals at GABRA4 (rs2055942: Padj-agesex-combined=3×10(-4)) and at KCTD8 (rs4695718: Padj-agesex-combined=2×10(-4)). Replication was observed for PRKD1 rs1953722 (proxy for rs10144903; Padj-agesex=0.031; Padj-agesex-combined=2×10(-4)). These genes may provide important functional leads in understanding disease pathogenesis in this population. PUBMED: 23937595
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