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

Srinivasan, Sundararajan ; Liju, Samuel ; Sathish, Natarajan ; Siddiqui, Moneeza K ; Anjana, Ranjit Mohan ; Pearson, Ewan R ; Doney, Alexander S F ; Mohan, Viswanathan ; Radha, Venkatesan ; Palmer, Colin N A

Diabetes care, 2023-08, Vol.46 (8), p.1515-1523 [Periódico revisado por pares]

United States: American Diabetes Association

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Título:
Common and Distinct Genetic Architecture of Age at Diagnosis of Diabetes in South Indian and European Populations
Autor: Srinivasan, Sundararajan ; Liju, Samuel ; Sathish, Natarajan ; Siddiqui, Moneeza K ; Anjana, Ranjit Mohan ; Pearson, Ewan R ; Doney, Alexander S F ; Mohan, Viswanathan ; Radha, Venkatesan ; Palmer, Colin N A
Assuntos: Age ; Age Factors ; Age of Onset ; Chromosome 10 ; Chromosome 6 ; Chromosomes ; Cultural differences ; Diabetes ; Diabetes mellitus ; Diabetes mellitus (non-insulin dependent) ; Diabetes Mellitus, Type 2 - diagnosis ; Diabetes Mellitus, Type 2 - ethnology ; Diabetes Mellitus, Type 2 - genetics ; Diagnosis ; Ethnicity ; European People - genetics ; Genetic Predisposition to Disease ; Genome-wide association studies ; Genome-Wide Association Study ; Genomes ; Heritability ; Humans ; Medical diagnosis ; Minority & ethnic groups ; Original ; Polygenic inheritance ; Polymorphism, Single Nucleotide ; Populations ; Research design ; South Asian People - genetics
É parte de: Diabetes care, 2023-08, Vol.46 (8), p.1515-1523
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SourceType-Scholarly Journals-1
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Descrição: 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. 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. 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. 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.
Editor: United States: American Diabetes Association
Idioma: Inglês;Chinês

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

Srinivasan, Sundararajan ; Liju, Samuel ; Sathish, Natarajan ; Siddiqui, Moneeza K ; Anjana, Ranjit Mohan ; Pearson, Ewan R ; Doney, Alexander S F ; Mohan, Viswanathan ; Radha, Venkatesan ; Palmer, Colin N A

United States: American Diabetes Association

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