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Genome-wide association study of retinopathy in individuals without diabetes


Jensen, RA and Sim, X and Li, X and Cotch, MF and Ikram, MK and Holliday, EG and Eiriksdottir, G and Harris, TB and Jonasson, F and Klein, BEK and Launer, LJ and Smith, AV and Boerwinkle, E and Cheung, N and Hewitt, AW and Liew, G and Mitchell, P and Wang, JJ and Attia, J and Scott, R and Glazer, NL and Lumley, T and McKnight, B and Psaty, BM and Taylor, K and Hofman, A and de Jong, PTVM and Rivadeneira, F and Uitterlinden, AG and Tay, WT and Teo, YY and Seielstad, M and Liu, J and Cheng, CY and Saw, SM and Aung, T and Ganesh, SK and O'Donnell, CJ and Nalls, MA and Wiggins, KL and Kuo, JZ and van Duijn, CM and Gudnason, V and Klein, R and Siscovick, DS and Rotter, J and Tai, ES and Vingerling, J and Wong, TY and The Blue Mountains Eye Study GWAS team; CKDGen Consortium, Genome-wide association study of retinopathy in individuals without diabetes, PLoS One, 8, (2) Article e54232. ISSN 1932-6203 (2013) [Refereed Article]


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Licensed under Creative Commons Attribution 3.0 Unported (CC BY 3.0)

DOI: doi:10.1371/journal.pone.0054232


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, -1.30.23 (beta standard error), p = 6.610-9. Evidence suggests this was a false positive finding. The minor allele frequency was low (∼2%), the quality of the imputation was moderate (r2 ~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.

Item Details

Item Type:Refereed Article
Research Division:Biomedical and Clinical Sciences
Research Group:Ophthalmology and optometry
Research Field:Ophthalmology
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Hewitt, AW (Professor Alex Hewitt)
ID Code:95065
Year Published:2013
Web of Science® Times Cited:10
Deposited By:Medicine
Deposited On:2014-09-23
Last Modified:2014-10-20
Downloads:426 View Download Statistics

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