A genome-wide association study of central corneal thickness in Latinos

作者：Gao Xiaoyi^*; Gauderman W James; Liu Yutao; Marjoram Paul; Torres Mina; Haritunians Talin; Kuo Jane Z; Chen Yii Der I; Allingham R Rand; Hauser Michael A; Taylor Kent D; Rotter Jerome I; Varma Rohit

来源：Investigative Ophthalmology & Visual Science, 2013, 54(4): 2435-2443.

DOI：10.1167/iovs.13-11692

PURPOSE: Central corneal thickness (CCT) is a clinically important risk factor for primary open angle glaucoma and keratoconus. Genetic factors controlling CCT in Latinos, the most populous minority population in the US, are unclear. Here we describe the first genome-wide association study (GWAS) report of CCT in Latinos.
METHODS: We performed a GWAS for CCT on 1768 Latinos recruited in the Los Angeles Latino Eye Study (LALES) using the Illumina HumanOmniExpress Beadchip (similar to 730K markers). To discover additional associated single nucleotide polymorphisms (SNPs), we imputed SNPs based on the 1,000 Genomes Project reference panels. All subjects were 40 years and older. We used linear regression with adjustment for age, sex and principal components of genetic ancestry.
RESULTS: We replicated the involvement of several previously reported loci, such as RXRA-COL5A1, FOXO1 and ZNF469, for CCT in Latinos (P<0.002). Moreover, we discovered novel SNPs, rs3118515, rs943423, rs3118594 and rs3132307, that reached GWAS significance (P < 5x10(-8)) in the uncharacterized LOC100506532 (gene type: miscRNA) for CCT in Latinos. By conditional analysis, we demonstrate that rs3118515 in this gene is responsible for the GWAS signal in the chromosome 9 RXRA-COL5A1 region in Latinos. Moreover, multiple sources of ENCODE evidence suggest that rs3118515 is in a regulatory region. Reverse-transcription PCR products indicated that transcripts of LOC100506532 surrounding rs3118515 were expressed in human cornea.
CONCLUSIONS: We discovered novel SNPs for CCT in Latinos and provided the first reported evidence of the corneal expression of LOC100506532. These results help to further increase our understanding of the genetic architecture of CCT.

• 出版日期2013-4
• 单位河北医科大学