Key result
Top South Asian polygenic risk score quartile linked to ~6-fold greater type 2 diabetes risk.
Why the study?
Genome-wide polygenic risk scores for lifestyle disorders like type 2 diabetes identify at-risk individuals early to guide healthier lifestyles, prompting the development and testing of a score specifically for the Indian population.
Does a genome-wide polygenic risk score accurately predict Type 2 Diabetes risk in the Indian population?
Case-Control (n=4,222)
Yes
Does a genome-wide polygenic risk score accurately predict Type 2 Diabetes risk in the Indian population?
A newly developed genome-wide polygenic risk score for Type 2 Diabetes demonstrates high predictive accuracy in the Indian population, offering a potential tool for personalized preventive strategies.
Answers are grounded in this paper and cite their sources.
PRS may aid T2D risk stratification in Indians; hypothesis-generating and requires prospective validation before clinical adoption.
Genome-wide polygenic risk scores (PRS) for lifestyle disorders, like Type 2 Diabetes (T2D), are useful in identifying at-risk individuals early on in life, and to guide them towards healthier lifestyles. The current study was aimed at developing PRS for the Indian population using imputed genotype data from UK Biobank and testing the developed PRS on data from GenomegaDB of Indians living in India. 959 T2D cases and 2,818 controls were selected from Indian participants of UK Biobank to develop the PRS. Summary statistics available for South Asians, from the DIAMANTE consortium, were used to weigh genetic variants. LDpred2 algorithm was used to adjust the effect of linkage disequilibrium among the variants. The association of PRS with T2D, after adjusting for age, sex and top ten genetic principal components, was found to be very significant (AUC = 0.7953, OR = 2.9856 [95% CI: 2.7044-3.2961]). When participants were divided into four PRS quartile groups, the odds of developing T2D increased sequentially with the higher PRS groups. The highest PRS group (top 25%) showed 5.79 fold increased risk compared to the rest of the participants (75%). The PRS derived using the same set of variants was found to be significantly associated with T2D in the test dataset of 445 Indians (AUC = 0.7781, OR = 1.6656 [95%CI = 0.6127-4.5278]). Our study demonstrates a framework to derive Indian-specific PRS for T2D. The accuracy of the derived PRS shows it's potential to be used as a prognostic metric to stratify individuals, and to recommend personalized preventive strategies.
No takes yet. Share an insight, caveat, or question.
Pemmasani et al. (2023) conducted a case-control in Type 2 Diabetes (n=4,222). High polygenic risk score (top 25%) vs. Lower polygenic risk score (bottom 75%) was evaluated on Type 2 diabetes risk (OR 5.79, 95% CI 4.86-6.90, p=< 2e-16). Individuals in the highest quartile of a South Asian-specific polygenic risk score had a 5.79-fold increased risk of developing type 2 diabetes compared to the remaining 75% of the population.
Synapse has enriched 10 related papers. Consider them for comparative context: