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BMC Med Genet. 2018 May 8;19(1):71. doi: 10.1186/s12881-018-0587-8.

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

Author information

1
Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.
2
Department of Ophthalmology, Flinders University, Flinders Medical Centre, Adelaide, South Australia, Australia.
3
Save Sight Institute, Clinical Ophthalmology and Eye Health, University of Sydney, Sydney, New South Wales, Australia.
4
Department of Ophthalmology, Royal Melbourne Hospital, Parkville, Victoria, Australia.
5
Academic Unit of Ophthalmology, Australian National University, Canberra, Australia.
6
School of Medical Sciences, University of NSW, Sydney, New South Wales, Australia.
7
Medical Retina Service, Moorfields Eye Hospital, London, UK.
8
NHMRC Clinical Trials Centre, University of Sydney, Camperdown, New South Wales, Australia.
9
St Vincent's Hospital, Fitzroy, Victoria, Australia.
10
Centre for Eye Research Australia, University of Melbourne, East Melbourne, Victoria, Australia.
11
Singapore Eye Research Institute, Singapore, Singapore.
12
Department of Endocrinology, Flinders University, Flinders Medical Centre, Adelaide, South Australia, Australia.
13
Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia.
14
Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia. Kathryn.Burdon@utas.edu.au.
15
Department of Ophthalmology, Flinders University, Flinders Medical Centre, Adelaide, South Australia, Australia. Kathryn.Burdon@utas.edu.au.

Abstract

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 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 × 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 × 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 PCSK2 (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.

KEYWORDS:

Diabetes complications; Diabetic retinopathy; Genetics; Genome-wide association study; Macular edema

PMID:
29739359
PMCID:
PMC5941644
DOI:
10.1186/s12881-018-0587-8
[Indexed for MEDLINE]
Free PMC Article

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