A U.K. study based on a group of British Pakistani and British Bangladeshi individuals suggests that polygenic risk scores (PRS) could help to predict diabetes risk in this group, but also highlights that more, large background studies are needed to ensure that all relevant genetic variants are identified.
South Asian people are disproportionately affected by type 2 diabetes and therefore identifying accurate methods for early risk detection could help many people improve their health and even stop initiation or progression of the condition.
There is a strong genetic component to type 2 diabetes, but despite South Asians being heavily affected, most previous genetic studies on type 2 diabetes have been carried out in majority European populations. This discrepancy causes problems, as while polygenic risk scores are useful tools for disease risk prediction, they are fed by large genome-wide association studies in mostly White populations so have uncertain accuracy in other ethnic groups.
Writing in PLoS Med, Sarah Finer, a senior lecturer at Queen Mary University of London, and colleagues evaluated whether genetic variants known to increase risk for type 2 diabetes in European populations are also relevant in British Pakistani and British Bangladeshi people.
Genes & Health is a large, population study of British Pakistanis and Bangladeshis with more than 20,000 participants. Both genomic and routine health data are collected from those in the study. Finer and colleagues assessed whether 27 areas in the genome linked to type 2 diabetes risk in Europeans were also linked in 18,875 participants of the Genes & Health cohort.
Notably, only nine of these 27 associations were also replicated in the Genes & Health cohort, suggesting that significant genetic differences are present between European and South Asian populations that impact diabetes risk. “Our work highlights the need for greater representation of diverse ancestry groups in genetic studies of type 2 diabetes,” write the authors.
In a second step, the researchers created and tested a polygenic risk score 13,648 using the British Pakistani and Bangladeshi data gathered in their study.
They found it did improve risk prediction to a modest degree, particularly in women who experienced gestational diabetes and in younger people. It also helped to identify specific disease subgroups at diagnosis that could allow better targeted therapy if validated and then used in the clinic.
“Our polygenic risk score has multiple potential uses, but importantly, it helped identify young, otherwise healthy, individuals who were in fact living at high risk of type 2 diabetes, one in 20 of whom might have been mistakenly labelled as low risk by current clinical risk tools,” write the authors.
“We hope to see polygenic risk scores being adopted in clinical care in the future, after careful evaluation to understand their potential to improve health outcomes cost-effectively, and with diverse populations who are at greatest need,” concludes Finer in a press statement.
