title: Association of variants in FRAP1 and PDGFRA with corneal curvature in Asian populations from Singapore.
abstract: 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.
authors.affiliation: Department of Statistics and Applied Probability, National University of Singapore, Blk S16, 6 Science Drive 2, 117546, Singapore.
authors.forename: Siyu
authors.initials: S
authors.lastname: Han
authors.forename: Peng
authors.initials: P
authors.lastname: Chen
authors.forename: Qiao
authors.initials: Q
authors.lastname: Fan
authors.forename: Chiea-Chuen
authors.initials: CC
authors.lastname: Khor
authors.forename: Xueling
authors.initials: X
authors.lastname: Sim
authors.forename: Wan-Ting
authors.initials: WT
authors.lastname: Tay
authors.forename: Rick Twee-Hee
authors.initials: RT
authors.lastname: Ong
authors.forename: Chen
authors.initials: C
authors.lastname: Suo
authors.forename: Liang-Kee
authors.initials: LK
authors.lastname: Goh
authors.forename: Raghavan
authors.initials: R
authors.lastname: Lavanya
authors.forename: Yingfeng
authors.initials: Y
authors.lastname: Zheng
authors.forename: Renyi
authors.initials: R
authors.lastname: Wu
authors.forename: Mark
authors.initials: M
authors.lastname: Seielstad
authors.forename: Eranga
authors.initials: E
authors.lastname: Vithana
authors.forename: Jianjun
authors.initials: J
authors.lastname: Liu
authors.forename: Kee-Seng
authors.initials: KS
authors.lastname: Chia
authors.forename: Jeannette Jen-Mai
authors.initials: JJ
authors.lastname: Lee
authors.forename: E-Shyong
authors.initials: ES
authors.lastname: Tai
authors.forename: Tien-Yin
authors.initials: TY
authors.lastname: Wong
authors.forename: Tin
authors.initials: T
authors.lastname: Aung
authors.forename: Yik-Ying
authors.initials: YY
authors.lastname: Teo
authors.forename: Seang-Mei
authors.initials: SM
authors.lastname: Saw
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D002648:Child; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics; D015331:Cohort Studies; D003316:Corneal Diseases / Q000208:ethnology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics* / Q000378:metabolism; D012846:Singapore / Q000208:ethnology; D058570:TOR Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: C546842:MTOR protein, human; D020796:Receptor, Platelet-Derived Growth Factor alpha; D058570:TOR Serine-Threonine Kinases