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T2D-associated genetic loci linked to upped risks of diabetic retinopathy

5 months ago

There is a significant association between type 2 diabetes (T2D)-related genetic loci and higher risks of diabetic retinopathy (DR), independent of traditional risk factors, a recent study has found.

Researchers conducted a case-control genetic association study to determine whether individuals with more diabetes genetic risk alleles had greater risk of developing DR. They evaluated the aggregate effects of multiple T2D-associated genetic variants on the DR risk among 1,528 participants with diabetes from the Singapore Epidemiology of Eye Diseases Study. Of these, 547 (35.8 percent) had DR.

Participants went through a comprehensive ocular examination, as well as dilated fundus photography. Using the modified Airlie House classification system, retinal photographs were graded to evaluate the presence and severity of DR following a standardized protocol.

Researchers identified a total of 76 previously discovered T2D-related single nucleotide polymorphisms (SNPs) and constructed multilocus genetic risk scores (GRSs) for each individual. This was done by summing the number of risk alleles for each SNP weighted by the respective effect estimates on DR.

There were two GRSs generated. These are overall GRS that included all 76 discovered T2D-related SNPs and Asian-specific GRS that included a subset of 55 SNPs previously found to be associated with T2D in East and/or South Asian ancestry populations.

Logistic regression analyses were used to determine the associations between the GSRs and DR. The area under the receiver operating characteristic curve (AUC) determined the discriminating ability of the GRSs. Odds ratios on DR were the primary outcome measures.

Compared with participants in the lowest tertile of the overall GRS, those in the top tertile were 2.56 times more likely to have DR. Compared with participants in the bottom tertile of the Asian-specific GRS, those in the top were 2.00 times more likely to have DR.

There was an association between higher DR severity levels and both GRSs. However, the AUC only improved slightly by 3 to 4 percent with the addition of the GRSs to traditional risk factors.

The findings may offer new insights to advance the understanding of the genetic pathogenesis of DR, according to researchers.

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