Association of variants in FRAP1 and PDGFRA with corneal curvature in Asian populations from Singapore.

Journal Article (Journal Article)

Corneal curvature (CC) is a key determinant of major eye diseases, such as keratoconus, myopia and corneal astigmatism. No prior studies have discovered the genes for CC. Here we report the findings from four genome-wide association studies of CC in 10 008 samples from three population groups in Singapore. Our discovery phase surveyed 2867 Chinese and 3072 Malays, allowing us to identify two loci that were associated with CC variation: FRAP1 on chromosome 1p36.2 and PDGFRA on chromosome 4q12. These findings were subsequently replicated in a validation study involving an additional 2953 Asian Indians and a further collection of 1116 Chinese children. The effect sizes of the identified variants were consistent across all four cohorts, with seven single nucleotide polymorphisms (SNPs) in FRAP1 (lead SNP: rs17036350, meta P-value = 4.06 × 10(-13)) and six SNPs in PDGFRA (lead SNP: rs2114039, meta P-value = 1.33 × 10(-9)) attaining genome-wide significance in the SNP-based meta-analysis of the four studies. This is the first genome-wide survey of CC variation and we have identified two implicated loci in three genetically diverse Asian populations, suggesting the presence of common genetic etiology across multiple populations.

Full Text

Duke Authors

Cited Authors

  • Han, S; Chen, P; Fan, Q; Khor, C-C; Sim, X; Tay, W-T; Ong, RT-H; Suo, C; Goh, L-K; Lavanya, R; Zheng, Y; Wu, R; Seielstad, M; Vithana, E; Liu, J; Chia, K-S; Lee, JJ-M; Tai, E-S; Wong, T-Y; Aung, T; Teo, Y-Y; Saw, S-M

Published Date

  • September 15, 2011

Published In

Volume / Issue

  • 20 / 18

Start / End Page

  • 3693 - 3698

PubMed ID

  • 21665993

Electronic International Standard Serial Number (EISSN)

  • 1460-2083

Digital Object Identifier (DOI)

  • 10.1093/hmg/ddr269


  • eng

Conference Location

  • England