Common and distinct genetic architecture of age at diagnosis of diabetes in South Indian: and European populations

Sundar Srinivasan, Samuel Liju, Natarajan Sathish, Moneeza K. Siddiqui, Ranjit Mohan Anjana, Ewan R. Pearson, Alexander S. F. Doney, Viswanathan Mohan, Radha Venkatesan, Colin N. A. Palmer (Lead / Corresponding author)

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Abstract

Objective: South Asians are diagnosed with type 2 diabetes (T2D) more than a decade earlier in life than seen in European populations. We hypothesized that studying the genomics of age of diagnosis in these populations may give insight into the earlier age diagnosis of T2D among individuals of South Asian descent.

Research design and methods: We conducted a meta-analysis of genome-wide association studies (gwas) of age at diagnosis of t2 d in 34,001 individuals from four independent cohorts of european and south asian indians.

Results: We identified two signals near the tcf7 l2 and cdkal1 genes associated with age at the onset of t2 d. the strongest genome-wide significant variants at chromosome 10q25.3 in tcf7 l2 (rs7903146; p = 2.4 × 10−12, β = −0.436; se 0.02) and chromosome 6p22.3 in cdkal1 (rs9368219; p = 2.29 × 10−8; β = −0.053; se 0.01) were directionally consistent across ethnic groups and present at similar frequencies; however, both loci harbored additional independent signals that were only present in the south indian cohorts. A genome-wide signal was also obtained at chromosome 10q26.12 in wdr11 (rs3011366; p = 3.255 × 10−8; β = 1.44; se 0.25), specifically in the south indian cohorts. Heritability estimates for the age at diagnosis were much stronger in south indians than europeans, and a polygenic risk score constructed based on south indian gwas explained ∼2% trait variance.

Conclusions: Our findings provide a better understanding of ethnic differences in the age at diagnosis and indicate the potential importance of ethnic differences in the genetic architecture underpinning t2 d.
Original languageEnglish
Pages (from-to)1515–1523
Number of pages9
JournalDiabetes Care
Volume46
Issue number8
Early online date12 Jun 2023
DOIs
Publication statusPublished - Aug 2023

ASJC Scopus subject areas

  • Advanced and Specialised Nursing
  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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