TY - JOUR T1 - Genome-wide association study of retinopathy in individuals without diabetes. JF - PLoS One Y1 - 2013 A1 - Jensen, Richard A A1 - Sim, Xueling A1 - Li, Xiaohui A1 - Cotch, Mary Frances A1 - Ikram, M Kamran A1 - Holliday, Elizabeth G A1 - Eiriksdottir, Gudny A1 - Harris, Tamara B A1 - Jonasson, Fridbert A1 - Klein, Barbara E K A1 - Launer, Lenore J A1 - Smith, Albert Vernon A1 - Boerwinkle, Eric A1 - Cheung, Ning A1 - Hewitt, Alex W A1 - Liew, Gerald A1 - Mitchell, Paul A1 - Wang, Jie Jin A1 - Attia, John A1 - Scott, Rodney A1 - Glazer, Nicole L A1 - Lumley, Thomas A1 - McKnight, Barbara A1 - Psaty, Bruce M A1 - Taylor, Kent A1 - Hofman, Albert A1 - de Jong, Paulus T V M A1 - Rivadeneira, Fernando A1 - Uitterlinden, André G A1 - Tay, Wan-Ting A1 - Teo, Yik Ying A1 - Seielstad, Mark A1 - Liu, Jianjun A1 - Cheng, Ching-Yu A1 - Saw, Seang-Mei A1 - Aung, Tin A1 - Ganesh, Santhi K A1 - O'Donnell, Christopher J A1 - Nalls, Mike A A1 - Wiggins, Kerri L A1 - Kuo, Jane Z A1 - van Duijn, Cornelia M A1 - Gudnason, Vilmundur A1 - Klein, Ronald A1 - Siscovick, David S A1 - Rotter, Jerome I A1 - Tai, E Shong A1 - Vingerling, Johannes A1 - Wong, Tien Y KW - Aged KW - Aged, 80 and over KW - Female KW - Genome-Wide Association Study KW - Genotype KW - Histone Deacetylases KW - Humans KW - Hypertension KW - Male KW - Polymorphism, Single Nucleotide KW - Repressor Proteins KW - Retinal Diseases AB -

BACKGROUND: Mild retinopathy (microaneurysms or dot-blot hemorrhages) is observed in persons without diabetes or hypertension and may reflect microvascular disease in other organs. We conducted a genome-wide association study (GWAS) of mild retinopathy in persons without diabetes.

METHODS: A working group agreed on phenotype harmonization, covariate selection and analytic plans for within-cohort GWAS. An inverse-variance weighted fixed effects meta-analysis was performed with GWAS results from six cohorts of 19,411 Caucasians. The primary analysis included individuals without diabetes and secondary analyses were stratified by hypertension status. We also singled out the results from single nucleotide polymorphisms (SNPs) previously shown to be associated with diabetes and hypertension, the two most common causes of retinopathy.

RESULTS: No SNPs reached genome-wide significance in the primary analysis or the secondary analysis of participants with hypertension. SNP, rs12155400, in the histone deacetylase 9 gene (HDAC9) on chromosome 7, was associated with retinopathy in analysis of participants without hypertension, -1.3±0.23 (beta ± standard error), p = 6.6×10(-9). Evidence suggests this was a false positive finding. The minor allele frequency was low (∼2%), the quality of the imputation was moderate (r(2) ∼0.7), and no other common variants in the HDAC9 gene were associated with the outcome. SNPs found to be associated with diabetes and hypertension in other GWAS were not associated with retinopathy in persons without diabetes or in subgroups with or without hypertension.

CONCLUSIONS: This GWAS of retinopathy in individuals without diabetes showed little evidence of genetic associations. Further studies are needed to identify genes associated with these signs in order to help unravel novel pathways and determinants of microvascular diseases.

VL - 8 IS - 2 U1 - http://www.ncbi.nlm.nih.gov/pubmed/23393555?dopt=Abstract ER -