Dataset Information

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

ABSTRACT:

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.

SUBMITTER: Jensen RA

PROVIDER: S-EPMC3564946 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Publications

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

Jensen Richard A RA Sim Xueling X Li Xiaohui X Cotch Mary Frances MF Ikram M Kamran MK Holliday Elizabeth G EG Eiriksdottir Gudny G Harris Tamara B TB Jonasson Fridbert F Klein Barbara E K BE Launer Lenore J LJ Smith Albert Vernon AV Boerwinkle Eric E Cheung Ning N Hewitt Alex W AW Liew Gerald G Mitchell Paul P Wang Jie Jin JJ Attia John J Scott Rodney R Glazer Nicole L NL Lumley Thomas T McKnight Barbara B Psaty Bruce M BM Taylor Kent K Hofman Albert A de Jong Paulus T V M PT Rivadeneira Fernando F Uitterlinden Andre G AG Tay Wan-Ting WT Teo Yik Ying YY Seielstad Mark M Liu Jianjun J Cheng Ching-Yu CY Saw Seang-Mei SM Aung Tin T Ganesh Santhi K SK O'Donnell Christopher J CJ Nalls Mike A MA Wiggins Kerri L KL Kuo Jane Z JZ van Duijn Cornelia M CM Gudnason Vilmundur V Klein Ronald R Siscovick David S DS Rotter Jerome I JI Tai E Shong ES Vingerling Johannes J Wong Tien Y TY

PloS one 20130205 2

<h4>Background</h4>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.<h4>Methods</h4>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 r ...[more]

PMID: 23393555

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Project description:Both asthma and obesity are complex disorders that are influenced by environmental and genetic factors. Shared genetic factors between asthma and obesity have been proposed to partly explain epidemiological findings of co-morbidity between these conditions.To identify genetic variants that are associated with body mass index (BMI) in asthmatic children and adults, and to evaluate if there are differences between the genetics of BMI in asthmatics and healthy individuals.In total, 19 studies contributed with genome-wide analysis study (GWAS) data from more than 23 000 individuals with predominantly European descent, of whom 8165 are asthmatics.We report associations between several DENND1B variants (P = 2.2 × 10(-7) for rs4915551) on chromosome 1q31 and BMI from a meta-analysis of GWAS data using 2691 asthmatic children (screening data). The top DENND1B single nucleotide polymorphisms(SNPs) were next evaluated in seven independent replication data sets comprising 2014 asthmatics, and rs4915551 was nominally replicated (P < 0.05) in two of the seven studies and of borderline significance in one (P = 0.059). However, strong evidence of effect heterogeneity was observed and overall, the association between rs4915551 and BMI was not significant in the total replication data set, P = 0.71. Using a random effects model, BMI was overall estimated to increase by 0.30 kg/m(2) (P = 0.01 for combined screening and replication data sets, N = 4705) per additional G allele of this DENND1BSNP. FTO was confirmed as an important gene for adult and childhood BMI regardless of asthma status.DENND1B was recently identified as an asthma susceptibility gene in a GWAS on children, and here, we find evidence that DENND1B variants may also be associated with BMI in asthmatic children. However, the association was overall not replicated in the independent data sets and the heterogeneous effect of DENND1B points to complex associations with the studied diseases that deserve further study.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

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