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Genome-wide association study of retinopathy in individuals without diabetes.

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Authors
Jensen, Richard A
Sim, Xueling
Li, Xiaohui
Cotch, Mary Frances
Ikram, M Kamran
Holliday, Elizabeth G
Eiriksdottir, Gudny
Harris, Tamara B
Jonasson, Fridbert
Klein, Barbara E K
Launer, Lenore J
Smith, Albert Vernon
Boerwinkle, Eric
Cheung, Ning
Hewitt, Alex W
Liew, Gerald
Mitchell, Paul
Wang, Jie Jin
Attia, John
Scott, Rodney
Glazer, Nicole L
Lumley, Thomas
McKnight, Barbara
Psaty, Bruce M
Taylor, Kent
Hofman, Albert
de Jong, Paulus T V M
Rivadeneira, Fernando
Uitterlinden, Andre G
Tay, Wan-Ting
Teo, Yik Ying
Seielstad, Mark
Liu, Jianjun
Cheng, Ching-Yu
Saw, Seang-Mei
Aung, Tin
Ganesh, Santhi K
O'Donnell, Christopher J
Nalls, Mike A
Wiggins, Kerri L
Kuo, Jane Z
van Duijn, Cornelia M
Gudnason, Vilmundur
Klein, Ronald
Siscovick, David S
Rotter, Jerome I
Tai, E Shong
Vingerling, Johannes
Wong, Tien Y
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Issue Date
2013

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Citation
PLoS ONE 2013, 8 (2):e54232
Abstract
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.
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.
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.
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.
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http://dx.doi.org/10.1371/journal.pone.0054232
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3564946/
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openAccess
ae974a485f413a2113503eed53cd6c53
10.1371/journal.pone.0054232
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