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Genome-wide association studies for diabetic macular edema and proliferative diabetic retinopathy

Graham, Patricia; Kaidonis, Georgia; Abhary, Sotoodeh; Gillies, Mark C; Daniell, Mark; Essex, Rohan; Chang, John H.; Lake, Stewart; Pal, Bishwanath; Jenkins, Alicia; Hewitt, Alex W

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Background: Diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) are sight threatening complications of diabetes mellitus and leading causes of adult onset blindness worldwide. Genetic risk factors for diabetic retinopathy (DR) have been described previously, but have been difficult to replicate between studies, which have often used composite phenotypes and been conducted in different populations. This study aims to identify genetic risk factors for DME and PDR as separate...[Show more]

dc.contributor.authorGraham, Patricia
dc.contributor.authorKaidonis, Georgia
dc.contributor.authorAbhary, Sotoodeh
dc.contributor.authorGillies, Mark C
dc.contributor.authorDaniell, Mark
dc.contributor.authorEssex, Rohan
dc.contributor.authorChang, John H.
dc.contributor.authorLake, Stewart
dc.contributor.authorPal, Bishwanath
dc.contributor.authorJenkins, Alicia
dc.contributor.authorHewitt, Alex W
dc.date.accessioned2019-05-07T03:50:41Z
dc.date.available2019-05-07T03:50:41Z
dc.identifier.issn1471-2350
dc.identifier.urihttp://hdl.handle.net/1885/160898
dc.description.abstractBackground: Diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) are sight threatening complications of diabetes mellitus and leading causes of adult onset blindness worldwide. Genetic risk factors for diabetic retinopathy (DR) have been described previously, but have been difficult to replicate between studies, which have often used composite phenotypes and been conducted in different populations. This study aims to identify genetic risk factors for DME and PDR as separate complications in Australians of European descent with type 2 diabetes. Methods: Caucasian Australians with type 2 diabetes were evaluated in a genome wide association study (GWAS) to compare 270 DME cases and 176 PDR cases with 435 non retinopathy controls. All participants were genotyped by SNP array and after data cleaning, cases were compared to controls using logistic regression adjusting for relevant covariates. Results: The top ranked SNP for DME was rs1990145 (p = 4.10 x 10(-6), OR = 2.02 95%CI [1.50, 2.72]) on chromosome 2. The top-ranked SNP for PDR was rs918519 (p = 3.87 x 10(-6), OR = 0.35 95%CI [0.22, 0.54]) on chromosome 5. A trend towards association was also detected at two SNPs reported in the only other reported GWAS of DR in Caucasians; rs12267418 near MALRD1 (p = 0.008) in the DME cohort and rs16999051 in the diabetes gene PCSK.2 (p = 0.007) in the PDR cohort. Conclusion: This study has identified loci of interest for DME and PDR, two common ocular complications of diabetes. These findings require replication in other Caucasian cohorts with type 2 diabetes and larger cohorts will be required to identify genetic loci with statistical confidence. There is considerable overlap in the patient cohorts with each retinopathy subtype, complicating the search for genes that contribute to PDR and DME biology.
dc.format.mimetypeapplication/pdf
dc.language.isoen_AU
dc.publisherBioMed Central
dc.rights© 2018. The Author(s).
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceBMC Medical Genetics
dc.titleGenome-wide association studies for diabetic macular edema and proliferative diabetic retinopathy
dc.typeJournal article
local.description.notesImported from ARIES
local.identifier.citationvolume19
dc.date.issued2018
local.identifier.absfor110311 - Medical Genetics (excl. Cancer Genetics)
local.identifier.ariespublicationu5369653xPUB96
local.type.statusPublished Version
local.contributor.affiliationGraham, Patricia, University of Tasmania
local.contributor.affiliationKaidonis, Georgia, Flinders University
local.contributor.affiliationAbhary, Sotoodeh, Flinders University
local.contributor.affiliationGillies, Mark C, University of Sydney
local.contributor.affiliationDaniell, Mark, Royal Melbourne Hospital
local.contributor.affiliationEssex, Rohan, College of Health and Medicine, ANU
local.contributor.affiliationChang, John H., University of New South Wales
local.contributor.affiliationLake, Stewart, Flinders University
local.contributor.affiliationPal, Bishwanath, Moorfields Eye Hospital
local.contributor.affiliationJenkins, Alicia, St Vincent’s Hospital
local.contributor.affiliationHewitt, Alex W., University of Melbourne
dc.relationhttp://purl.org/au-research/grants/nhmrc/595918
local.bibliographicCitation.issue71
local.identifier.doi10.1186/s12881-018-0587-8
local.identifier.absseo920104 - Diabetes
dc.date.updated2019-03-12T07:37:19Z
local.identifier.scopusID2-s2.0-85046634231
dcterms.accessRightsOpen Access
dc.provenancehttp://sherpa.ac.uk/romeo/issn/1471-2350/..."author can archive publisher's version/PDF" from SHERPA/RoMEO site (as at 7/5/19)
dc.rights.licenseCreative Commons Attribution 4.0 International License
CollectionsANU Research Publications

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