Advertisement

 

 

Exome-chip association analysis reveals an Asian-specific missense variant in PAX4 associated with type 2 diabetes in Chinese individuals.

Exome-chip association analysis reveals an Asian-specific missense variant in PAX4 associated with type 2 diabetes in Chinese individuals.
Author Information (click to view)

Cheung CY, Tang CS, Xu A, Lee CH, Au KW, Xu L, Fong CH, Kwok KH, Chow WS, Woo YC, Yuen MM, Hai JS, Jin YL, Cheung BM, Tan KC, Cherny SS, Zhu F, Zhu T, Thomas GN, Cheng KK, Jiang CQ, Lam TH, Tse HF, Sham PC, Lam KS,


Cheung CY, Tang CS, Xu A, Lee CH, Au KW, Xu L, Fong CH, Kwok KH, Chow WS, Woo YC, Yuen MM, Hai JS, Jin YL, Cheung BM, Tan KC, Cherny SS, Zhu F, Zhu T, Thomas GN, Cheng KK, Jiang CQ, Lam TH, Tse HF, Sham PC, Lam KS, (click to view)

Cheung CY, Tang CS, Xu A, Lee CH, Au KW, Xu L, Fong CH, Kwok KH, Chow WS, Woo YC, Yuen MM, Hai JS, Jin YL, Cheung BM, Tan KC, Cherny SS, Zhu F, Zhu T, Thomas GN, Cheng KK, Jiang CQ, Lam TH, Tse HF, Sham PC, Lam KS,

Advertisement
Share on FacebookTweet about this on TwitterShare on LinkedIn

Diabetologia 2016 Oct 15()
Abstract
AIMS/HYPOTHESIS
Genome-wide association studies (GWASs) have identified many common type 2 diabetes-associated variants, mostly at the intronic or intergenic regions. Recent advancements of exome-array genotyping platforms have opened up a novel means for detecting the associations of low-frequency or rare coding variants with type 2 diabetes. We conducted an exomechip association analysis to identify additional type 2 diabetes susceptibility variants in the Chinese population.

METHODS
An exome-chip association study was conducted by genotyping 5640 Chinese individuals from Hong Kong, using a custom designed exome array, the Asian Exomechip. Single variant association analysis was conducted on 77,468 single nucleotide polymorphisms (SNPs). Fifteen SNPs were subsequently genotyped for replication analysis in an independent Chinese cohort comprising 12,362 individuals from Guangzhou. A combined analysis involving 7189 cases and 10,813 controls was performed.

RESULTS
In the discovery stage, an Asian-specific coding variant rs2233580 (p.Arg192His) in PAX4, and two variants at the known loci, CDKN2B-AS1 and KCNQ1, were significantly associated with type 2 diabetes with exome-wide significance (p discovery < 6.45 × 10(-7)). The risk allele (T) of PAX4 rs2233580 was associated with a younger age at diabetes diagnosis. This variant was replicated in an independent cohort and demonstrated a stronger association that reached genome-wide significance (p meta-analysis [p meta] = 3.74 × 10(-15)) in the combined analysis. CONCLUSIONS/INTERPRETATION
We identified the association of a PAX4 Asian-specific missense variant rs2233580 with type 2 diabetes in an exome-chip association analysis, supporting the involvement of PAX4 in the pathogenesis of type 2 diabetes. Our findings suggest PAX4 is a possible effector gene of the 7q32 locus, previously identified from GWAS in Asians.

Submit a Comment

Your email address will not be published. Required fields are marked *

ten + 11 =

[ HIDE/SHOW ]