Dataset Information

Common and Distinct Genetic Architecture of Age at Diagnosis of Diabetes in South Indian and European Populations.

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 T2D in 34,001 individuals from four independent cohorts of European and South Asian Indians.

Results

We identified two signals near the TCF7L2 and CDKAL1 genes associated with age at the onset of T2D. The strongest genome-wide significant variants at chromosome 10q25.3 in TCF7L2 (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 T2D.

SUBMITTER: Srinivasan S

PROVIDER: S-EPMC10369131 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Publications

Common and Distinct Genetic Architecture of Age at Diagnosis of Diabetes in South Indian and European Populations.

Srinivasan Sundararajan S Liju Samuel S Sathish Natarajan N Siddiqui Moneeza K MK Anjana Ranjit Mohan RM Pearson Ewan R ER Doney Alexander S F ASF Mohan Viswanathan V Radha Venkatesan V Palmer Colin N A CNA

Diabetes care 20230801 8

<h4>Objective</h4>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.<h4>Research design and methods</h4>We conducted a meta-analysis of genome-wide association studies (GWAS) of age at diagnosis of T2D in 34,001 individuals from four independent ...[more]

PMID: 37308106

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Project description:Pollution and other anthropogenic effects have driven a decrease in Atlantic salmon (Salmo salar) in the Iberian Peninsula. The restocking effort carried out in the 1980s, with salmon from northern latitudes with the aim of mitigating the decline of native populations, failed, probably due to the deficiency in adaptation of foreign salmon from northern Europe to the warm waters of the Iberian Peninsula. This result would imply that the Iberian populations of Atlantic salmon have experienced local adaptation in their past evolutionary history, as has been described for other populations of this species and other salmonids. Local adaptation can occur by divergent selections between environments, favoring the fixation of alleles that increase the fitness of a population in the environment it inhabits relative to other alleles favored in another population. In this work, we compared the genomes of different populations from the Iberian Peninsula (Atlantic and Cantabric basins) and Scotland in order to provide tentative evidence of candidate SNPs responsible for the adaptive differences between populations, which may explain the failures of restocking carried out during the 1980s. For this purpose, the samples were genotyped with a 220,000 high-density SNP array (Affymetrix) specific to Atlantic salmon. Our results revealed potential evidence of local adaptation for North Spanish and Scottish populations. As expected, most differences concerned the comparison of the Iberian Peninsula with Scotland, although there were also differences between Atlantic and Cantabric populations. A high proportion of the genes identified are related to development and cellular metabolism, DNA transcription and anatomical structure. A particular SNP was identified within the NADP-dependent malic enzyme-2 (mMEP-2*), previously reported by independent studies as a candidate for local adaptation in salmon from the Iberian Peninsula. Interestingly, the corresponding SNP within the mMEP-2* region was consistent with a genomic pattern of divergent selection.

Dataset Information

Common and Distinct Genetic Architecture of Age at Diagnosis of Diabetes in South Indian and European Populations.

Objective

Research design and methods

Results

Conclusions

Publications

Common and Distinct Genetic Architecture of Age at Diagnosis of Diabetes in South Indian and European Populations.

Similar Datasets

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