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Genome-wide association analyses identify three new susceptibility loci for primary angle closure glaucoma.

ABSTRACT: Primary angle closure glaucoma (PACG) is a major cause of blindness worldwide. We conducted a genome-wide association study including 1,854 PACG cases and 9,608 controls across 5 sample collections in Asia. Replication experiments were conducted in 1,917 PACG cases and 8,943 controls collected from a further 6 sample collections. We report significant associations at three new loci: rs11024102 in PLEKHA7 (per-allele odds ratio (OR)=1.22; P=5.33×10(-12)), rs3753841 in COL11A1 (per-allele OR=1.20; P=9.22×10(-10)) and rs1015213 located between PCMTD1 and ST18 on chromosome 8q (per-allele OR=1.50; P=3.29×10(-9)). Our findings, accumulated across these independent worldwide collections, suggest possible mechanisms explaining the pathogenesis of PACG.

SUBMITTER: Vithana EN

PROVIDER: S-EPMC4333205 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

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Genome-wide association analyses identify three new susceptibility loci for primary angle closure glaucoma.

Vithana Eranga N EN Khor Chiea-Chuen CC Qiao Chunyan C Nongpiur Monisha E ME George Ronnie R Chen Li-Jia LJ Do Tan T Abu-Amero Khaled K Huang Chor Kai CK Low Sancy S Tajudin Liza-Sharmini A LA Perera Shamira A SA Cheng Ching-Yu CY Xu Liang L Jia Hongyan H Ho Ching-Lin CL Sim Kar Seng KS Wu Ren-Yi RY Tham Clement C Y CCY Chew Paul T K PTK Su Daniel H DH Oen Francis T FT Sarangapani Sripriya S Soumittra Nagaswamy N Osman Essam A EA Wong Hon-Tym HT Tang Guangxian G Fan Sujie S Meng Hailin H Huong Dao T L DTL Wang Hua H Feng Bo B Baskaran Mani M Shantha Balekudaru B Ramprasad Vedam L VL Kumaramanickavel Govindasamy G Iyengar Sudha K SK How Alicia C AC Lee Kelvin Y KY Sivakumaran Theru A TA Yong Victor H K VHK Ting Serena M L SML Li Yang Y Wang Ya-Xing YX Tay Wan-Ting WT Sim Xueling X Lavanya Raghavan R Cornes Belinda K BK Zheng Ying-Feng YF Wong Tina T TT Loon Seng-Chee SC Yong Vernon K Y VKY Waseem Naushin N Yaakub Azhany A Chia Kee-Seng KS Allingham R Rand RR Hauser Michael A MA Lam Dennis S C DSC Hibberd Martin L ML Bhattacharya Shomi S SS Zhang Mingzhi M Teo Yik Ying YY Tan Donald T DT Jonas Jost B JB Tai E-Shyong ES Saw Seang-Mei SM Hon Do Nhu DN Al-Obeidan Saleh A SA Liu Jianjun J Chau Tran Nguyen Bich TNB Simmons Cameron P CP Bei Jin-Xin JX Zeng Yi-Xin YX Foster Paul J PJ Vijaya Lingam L Wong Tien-Yin TY Pang Chi-Pui CP Wang Ningli N Aung Tin T

Nature genetics 20120826 10

Primary angle closure glaucoma (PACG) is a major cause of blindness worldwide. We conducted a genome-wide association study including 1,854 PACG cases and 9,608 controls across 5 sample collections in Asia. Replication experiments were conducted in 1,917 PACG cases and 8,943 controls collected from a further 6 sample collections. We report significant associations at three new loci: rs11024102 in PLEKHA7 (per-allele odds ratio (OR)=1.22; P=5.33×10(-12)), rs3753841 in COL11A1 (per-allele OR=1.20; ...[more]

PMID: 22922875

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Project description:PURPOSE:Recent genome-wide association studies (GWAS) have verified eight genetic loci that were significantly associated with primary angle-closure glaucoma (PACG). The present study investigated whether these variants are associated with the ocular biometric parameters of anterior chamber depth (ACD) and axial length (AL) in a northern Chinese population, as well as whether there were differences in the association of genetic markers in our cohort based on ethnicity. METHODS:A case-control association study of 500 patients and 720 controls was undertaken. All individuals were genotyped for eight single nucleotide polymorphisms (SNPs) (rs11024102 in PLEKHA7, rs3753841 in COL11A1, rs1015213 located between PCMTD1 and ST18, rs3816415 in EPDR1, rs1258267 in CHAT, rs736893 in GLIS3, rs7494379 in FERMT2, and rs3739821 mapping between DPM2 and FAM102A) using an improved multiplex ligation detection reaction (iMLDR) technique. Allelic and genotypic frequency differences were evaluated using a logistic regression model. Generalized estimation equation (GEE) analysis was conducted for association testing between genotypes and ocular biometric parameters. False discovery rate (FDR) correction for multiple comparisons was employed, and the statistical power was calculated via power and sample size calculation. RESULTS:Four of the eight SNPs, rs3753841, rs1258267, rs736893 and rs7494379, were associated with PACG (p = 0.007, 0.0016, 0.0045, 0.045, respectively), and only rs3753841, rs1258267 and rs736893 surpassed the FDR correction. For subgroup analysis, only rs1258267 could withstand multiple testing correction in the Han nationality (p = 0.00571). In the GEE tests, rs3753841, rs1258267 and rs736893 were found to be nominally associated with ACD (p = 0.023, 0.016, 0.01, respectively). However, these associations could not survive FDR correction. CONCLUSIONS:The SNP rs3753841 in COL11A1, rs1258267 in CHAT and rs736893 in GLIS3 are associated with PACG in northern Chinese people, and the association of genetic markers manifests a tendency of ethnic diversity. Larger population-based studies are warranted to reveal additional PACG loci and ethnic aspects of PACG.

Dataset Information

Genome-wide association analyses identify three new susceptibility loci for primary angle closure glaucoma.

Publications

Genome-wide association analyses identify three new susceptibility loci for primary angle closure glaucoma.

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