Genome-wide association study in a Chinese population with diabetic retinopathy

Abstract

Diabetic retinopathy (DR) is a leading cause of preventable blindness in adults. To identify genetic contributions in DR, we studied 2071 type 2 diabetics. We first conducted a genome-wide association study of 1007 individuals, comparing 570 subjects with ≥8 years duration without DR (controls) with 437 PDR (cases) in the Chinese discovery cohort. Cases and controls were similar for HbA1c, diabetes duration and body mass index. Association analysis with imputed data identified three novel loci: TBC1D4-COMMD6-UCHL3 (rs9565164, P = 1.3 × 10(-7)), LRP2-BBS5 (rs1399634, P = 2.0 × 10(-6)) and ARL4C-SH3BP4 (rs2380261, P = 2.1 × 10(-6)). Analysis of an independent cohort of 585 Hispanics diabetics with or without DR though did not confirm these signals. These genes are still of particular interest because they are involved in insulin regulation, inflammation, lipid signaling and apoptosis pathways, all of which are possibly involved with DR. Our finding nominates possible novel loci as potential DR susceptibility genes in the Chinese that are independent of the level of HbA1c and duration of diabetes and may provide insight into the pathophysiology of DR.

Genome-wide association study for sight-threatening diabetic retinopathy reveals association with genetic variation near the GRB2 gene

“…Of note, four of the previously published studies were conducted in non-European populations (Chinese [17], Taiwanese [18], Japanese [19] and Mexican American [15]), while one was predominantly in patients with type 1 diabetes mellitus [16]. These fundamental differences may explain the lack of replication observed not only with the current study, but also with each other.…”

“…We first assessed loci reported in previous GWAS of diabetic retinopathy [15][16][17][18][19] for association in the current study in an attempt to replicate previous findings. A p value of <0.002 was required to account for the 29 loci assessed.…”

“…Several other GWAS for diabetic retinopathy have been published [15][16][17][18][19], although none report a genome-wide significant signal at 17q25. Of note, four of the previously published studies were conducted in non-European populations (Chinese [17], Taiwanese [18], Japanese [19] and Mexican American [15]), while one was predominantly in patients with type 1 diabetes mellitus [16].…”

“…Three recent genome-wide association studies (GWAS) for diabetic retinopathy have reported loci of interest that did not meet the statistical thresholds for genome-wide significance [15][16][17]. A study in a cohort of Taiwanese type 2 diabetes patients and a meta-analysis of Japanese patients identified several loci reaching significance, but these findings have not been validated in an independent cohort [18,19].…”

A Genome-Wide Association Study for Diabetic Retinopathy in a Japanese Population: Potential Association with a Long Intergenic Non-Coding RNA

“…Recently, several genome-wide association studies (GWAS) in Mexican-Americans [21], Chinese [22], [23] and Caucasians [24] identified multiple susceptibility loci to DR; however, none of these loci reached the genome-wide significance level, and none has been replicated in other studies [14].…”