Attia, John

Aung, Tin

Blue Mountains Eye Study GWAS team

Boerwinkle, Eric

Cheng, Ching-Yu

Cheung, Ning

CKDGen Consortium

Cotch, Mary Frances

de Jong, Paulus T. V. M.

Eiriksdottir, Gudny

Ganesh, Santhi K.

Glazer, Nicole L.

Gudnason, Vilmundur

Harris, Tamara B.

Hewitt, Alex W.

Hofman, Albert

Holliday, Elizabeth G.

Ikram, M. Kamran

Jensen, Richard A.

Jonasson, Fridbert

Klein, Barbara E. K.

Klein, Ronald

Kuo, Jane Z.

Launer, Lenore J.

Li, Xiaohui

Liew, Gerald

Liu, Jianjun

Lumley, Thomas

McKnight, Barbara

Mitchell, Paul

Nalls, Mike A.

O'Donnell, Christopher Joseph

Psaty, Bruce M.

Rivadeneira, Fernando

Rotter, Jerome I.

Saw, Seang-Mei

Scott, Rodney

Seielstad, Mark

Sim, Xueling

Siscovick, David S.

Smith, Albert Vernon

Tai, E. Shong

Tay, Wan-Ting

Taylor, Kent

Teo, Yik Ying

Uitterlinden, Andre G.

van Duijn, Cornelia M.

Vingerling, Johannes

Wang, Jie Jin

Wiggins, Kerri L.

Wong, Tien Y.

PLoS ONE

PubMed

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 disease

teo, Yik Ying

O'Donnell, Christopher J.

NARCIS 

Genome-wide association study of retinopathy in individuals without diabetes

BackgroundMild 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.MethodsA 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.ResultsNo 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.ConclusionsThis 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

Richard A Jensen

Xueling Sim

Xiaohui Li

Mary Frances Cotch

M Kamran Ikram

Elizabeth G Holliday

Gudny Eiriksdottir

Tamara B Harris

Fridbert Jonasson

Barbara E K Klein

Lenore J Launer

Albert Vernon Smith

Eric Boerwinkle

Ning Cheung

Alex W Hewitt

Gerald Liew

Paul Mitchell

Jie Jin Wang

John Attia

Rodney Scott

Nicole L Glazer

Thomas Lumley

Barbara McKnight

Bruce M Psaty

Kent Taylor

Albert Hofman

Paulus T V M de Jong

Fernando Rivadeneira

Andre G Uitterlinden

Wan-Ting Tay

Yik Ying Teo

Mark Seielstad

Jianjun Liu

Ching-Yu Cheng

Seang-Mei Saw

Tin Aung

Santhi K Ganesh

Christopher J O'Donnell

Mike A Nalls

Kerri L Wiggins

Jane Z Kuo

Blue Mountains Eye Study GWAS Team

Cornelia M van Duijn

Vilmundur Gudnason

Ronald Klein

David S Siscovick

Jerome I Rotter

E Shong Tai

Johannes Vingerling

Tien Y Wong

Directory of Open Access Journals

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

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files.
This article is open access.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.National Institutes of Health (NIH) 	
N01-AG-12100 
National Institute on Aging Intramural Research Program at the NIH 	
ZIAAG007380 
ZIAEY000401 
National Eye Institute Intramural Research Program at the NIH 	
ZIAAG007380 
ZIAEY000401 
Hjartavernd (the Icelandic Heart Association) 	 
Althingi (the Icelandic Parliament) 	 
National Heart, Lung, and Blood Institute 	
HHSN268201100005C 
HHSN268201100006C 
HHSN268201100007C 
HHSN268201100008C 
HHSN268201100009C 
HHSN268201100010C 
HHSN268201100011C 
HHSN268201100012C 
R01HL087641 
R01HL59367 
R01HL086694 
National Human Genome Research Institute 	
U01HG004402 
National Institutes of Health 	
HHSN268200625226C 
National Institutes of Health and NIH Roadmap for Medical Research 	
UL1RR025005 
Australian National Health & Medical Research Council (NHMRC) 	
974159 
991407 
211069 
457349 
NHMRC 	
512423 
475604 
529912 
590204 
Wellcome Trust, UK as part of Wellcome Trust Case Control Consortium 	 
genotyping costs of the entire BMES population 	
085475/B/08/Z 
085475/08/Z 
National Heart, Lung, and Blood Institute (NHLBI) 	
N01-HC-85239 
N01-HC-85079 
N01-HC-85086 
N01-HC-35129 
N01 HC-15103 
N01 HC-55222 
N01-HC-75150 
N01-HC-45133 
NHLBI 	
HL080295 
HL075366 
HL087652 
HL105756 
N02-HL-6-4278 
National Institute on Aging 	
AG-023629 
AG-15928 
AG-20098 
AG-027058 
Clinical Translational Science Institute 	
UL1RR033176 
National Institute of Diabetes and Digestive and Kidney Diseases 	
DK063491 
Cedars-Sinai Board of Governors' Chair in Medical Genetics (JIR) 	 
Netherlands Organization of Scientific Research NWO 	
175.010.2005.011 
Erasmus Medical Center, Rotterdam 	 
Erasmus University, Rotterdam 	 
Netherlands Organization for Scientific Research 	 
Netherlands Organization for Health Research and Development 	 
Research Institute for Diseases in the Elderly 	 
Ministry of Education, Culture and Science 	 
Ministry for Health, Welfare and Sports 	 
European Commission (DG XII) the Netherlands 	 
Municipality of Rotterdam 	 
Lijf en Leven, Krimpen a/d Lek the Netherlands 	 
MD Fonds, Utrecht the Netherlands 	 
Oogfonds Nederland, Utrecht the Netherlands 	 
Stichting Nederlands Oogheelkundig Onderzoek, Nijmegen/Rotterdam the Netherlands 	 
Swart van Essen, Rotterdam the Netherlands 	 
Netherlands Organisation for Scientific Research the Netherlands 	 
Bevordering van Volkskracht, Rotterdam the Netherlands 	 
Blindenhulp, The Hague the Netherlands 	 
Rotterdamse Vereniging Blindenbelangen, Rotterdam the Netherlands 	 
OOG, The Hague the Netherlands 	 
Algemene Nederlandse Vereniging ter Voorkoming van Blindheid, Doorn the Netherlands 	 
Blinden-Penning, Amsterdam the Netherlands 	 
Blindenhulp, 's Gravenzande the Netherlands 	 
Henkes Stichting, Rotterdam the Netherlands 	 
Topcon Europe BV, Capelle aan de IJssel the Netherlands 	 
Medical Workshop BV, Groningen the Netherlands 	 
 	
N01 HC-95159 
 	
N01-HC-95169 
 	
RR-02415

Jensen, Richard A

Ikram, M Kamran

Holliday, Elizabeth G

Harris, Tamara B

Klein, Barbara E K

Launer, Lenore J

Hewitt, Alex W

Glazer, Nicole L

Psaty, Bruce M

de Jong, Paulus T V M

Uitterlinden, Andre G

Ganesh, Santhi K

O'Donnell, Christopher J

Nalls, Mike A

Wiggins, Kerri L

Kuo, Jane Z

van Duijn, Cornelia M

Siscovick, David S

Rotter, Jerome I

Tai, E Shong

Wong, Tien Y

Hirsla - Landspítali University Hospital

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.Version of Recor

Genome-Wide Association Study of Retinopathy in Individuals without Diabetes

Abstract

Similar works

Full text

Available Versions

NARCIS

Directory of Open Access Journals

Hirsla - Landspítali University Hospital

Harvard University - DASH

EUR Research Repository

Crossref

The Francis Crick Institute

EUR Research Repository