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Multicenter Study
. 2025 Mar 3;66(3):55.
doi: 10.1167/iovs.66.3.55.

Genome-Wide Association Study to Identify Genetic Variants Associated With Diabetic Maculopathy

Rajya L Gurung  1 , Charvi Nangia  2 , Tengda Cai  3 , Liesel M FitzGerald  1 , Bennet J McComish  1 , Ebony Liu  2 , Georgia Kaidonis  4 , Bronwyn Ridge  4 , Alex W Hewitt  5 , Brendan Vote  5 , Nitin Verma  5 , Jamie E Craig  4 , Colin N A Palmer  2 , Kathryn P Burdon  1 , Weihua Meng  2   3
Affiliations
Multicenter Study

Genome-Wide Association Study to Identify Genetic Variants Associated With Diabetic Maculopathy

Rajya L Gurung et al. Invest Ophthalmol Vis Sci. .

Abstract

Purpose: Diabetic maculopathy (including diabetic macular edema [DME]) is the leading cause of vision loss in people with diabetes. We aimed to identify the genetic determinants of diabetic maculopathy.

Methods: We conducted a genome-wide association study (GWAS) in two cohorts with a meta-analysis. The Australian cohort comprised 551 cases of DME and 599 controls recruited from the states of South Australia and Tasmania. The Scottish cohort comprised 1951 cases of diabetic maculopathy and 6541 controls from the Genetics of Diabetes Audit and Research in Tayside Scotland study (GoDARTS). Genotyping, imputation, and association analysis using logistic regression were conducted in each cohort, before combining summary statistics in a meta-analysis using the GWAMA package.

Results: A locus on chromosome 7 reached genome-wide significance in GoDARTS but showed the opposite direction of effect in the Australian cohort. The meta-analysis identified two suggestive associations (P < 5 × 10-6) for diabetic maculopathy risk with similar effect direction; one at chromosome 1 close to the RNU5E-1 gene and one at chromosome 13 upstream of the ERICH6B gene. The two loci were evaluated in silico for potential functional links to diabetic maculopathy. Both are located in regulatory regions and have annotations indicating regulatory functions. They are also expression quantitative trait locus (eQTLs) for genes plausibly involved in diabetic maculopathy pathogenesis, with links to folate metabolism and the regulation of VEGF.

Conclusions: The study suggests several promising SNPs and genes related to diabetic maculopathy risk. Despite being the largest genetic study of diabetic maculopathy to date, larger, homogeneous cohorts will be required to identify robust genetic risk loci for the disease.

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Conflict of interest statement

Disclosure: R. L. Gurung, None; C. Nangia, None; T. Cai, None; L.M. FitzGerald, None; B.J. McComish, None; E. Liu, None; G. Kaidonis, None; B. Ridge, None; A.W. Hewitt, None; B. Vote, None; N. Verma, None; J.E. Craig, None; C.N.A. Palmer, None; K.P. Burdon, None; W. Meng, None

Figures

Figure 1.
Figure 1.
Manhattan plot for association analysis of diabetic maculopathy. (A) Australian cohort (diabetic macular edema). (B) GoDARTS cohort (diabetic maculopathy). The x-axis represents chromosomal position, and the y-axis represents the −log10 (P values) of association for each SNP tested. The blue horizontal line corresponds to the threshold for genome-wide suggestive association (P ≤ 5 × 10−6).
Figure 2.
Figure 2.
Manhattan plot for meta-analysis for diabetic macular edema/maculopathy. The x-axis represents chromosomal position, and the y-axis represents the −log10 (P values) of association for each SNP tested. The blue horizontal line corresponds to the threshold for genome-wide suggestive association (P ≤ 5 × 10−6).
Figure 3.
Figure 3.
Plot of Mendelian Randomization results between extreme body mass index (EBMI) and diabetic macular edema/maculopathy. Five different color lines mean different statistical methods used within the MR framework. The IVW method shows a significant negative association, whereas other methods suggest consistency in effect direction. The significant results found in the IVW, weighted median, and simple median methods demonstrate a consistent negative effect of EBMI on diabetic macular edema/maculopathy. These results highlight the robustness of the negative association, although the methods differ in sensitivity and statistical power due to underlying assumptions and treatment of instrumental variable validity.
See this image and copyright information in PMC

References

    1. Yau JW, Rogers SL, Kawasaki R, et al. .. Global prevalence and major risk factors of diabetic retinopathy. Diabetes Care. 2012; 35(3): 556–564. - PMC - PubMed
    1. Gundogan FC, Yolcu U, Akay F, et al. .. Diabetic macular edema. Pak J Med Sci. 2016; 32(2): 505. - PMC - PubMed
    1. Klein R, Klein BE, Moss SE, Cruickshanks KJ.. The Wisconsin Epidemiologic Study of Diabetic Retinopathy: XVII: the 14-year incidence and progression of diabetic retinopathy and associated risk factors in type 1 diabetes. Ophthalmology. 1998; 105(10): 1801–1815. - PubMed
    1. Lachin JM, Genuth S, Nathan DM, Zinman B, Rutledge BN.. Effect of glycemic exposure on the risk of microvascular complications in the diabetes control and complications trial—revisited. Diabetes. 2008; 57(4): 995–1001. - PubMed
    1. Hobbs S, Mehta A, Patel A, Das A.. Proliferative diabetic retinopathy and diabetic macular edema: are these two different disease processes? A retrospective cross-sectional study. Invest Ophthalmol Vis Sci. 2016; 57(12): 1592.

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