Characterizing the genetic risk for Type 2 diabetes in a Malaysian multi-ethnic cohort

Noraidatulakma Abdullah @ Muda, Nor Azian Abdul Murad, J. Attia, C. Oldmeadow, Ezanee Azlina Mohamad Hanif, Saiful Effendi Syafruddin, N. Abd Jalal, N. Ismail, M. Ishak, A. Rahman A. Jamal, R. J. Scott, E. G. Holliday

Research output: Contribution to journalArticle

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Abstract

Aims: To characterize the association with Type 2 diabetes of known Type 2 diabetes risk variants in people in Malaysia of Malay, Chinese and Indian ancestry who participated in the Malaysian Cohort project. Methods: We genotyped 1604 people of Malay ancestry (722 cases, 882 controls), 1654 of Chinese ancestry (819 cases, 835 controls) and 1728 of Indian ancestry (851 cases, 877 controls). First, 62 candidate single-nucleotide polymorphisms previously associated with Type 2 diabetes were assessed for association via logistic regression within ancestral groups and then across ancestral groups using a meta-analysis. Second, estimated odds ratios were assessed for excess directional concordance with previously studied populations. Third, a genetic risk score aggregating allele dosage across the candidate single-nucleotide polymorphisms was tested for association within and across ancestral groups. Results: After Bonferroni correction, seven individual single-nucleotide polymorphisms were associated with Type 2 diabetes in the combined Malaysian sample. We observed a highly significant excess in concordance of effect directions between Malaysian and previously studied populations. The genetic risk score was strongly associated with Type 2 diabetes in all Malaysian groups, explaining from 1.0 to 1.7% of total Type 2 diabetes risk variance. Conclusion: This study suggests there is substantial overlap of the genetic risk alleles underlying Type 2 diabetes in Malaysian and other populations. What's new?: This is the first large-scale genetic study of Type 2 diabetes in a Malaysian population. We assessed 62 single-nucleotide polymorphisms (SNPs) previously associated with Type 2 diabetes for their association with the disease in 2392 patients with Type 2 diabetes and 2594 control subjects of Malay, Chinese and Indian ancestry. Seven individual SNPs were associated with Type 2 diabetes after multiple testing adjustment. We observed highly significant excess in concordance of allelic effect directions between Malaysian and previously studied populations (P = 1 x 10<sup>-8</sup>). A genetic risk score including the 62 SNPs showed strong association in the Malaysian sample (P = 2 x 10<sup>-16</sup>) and explained 1.0-1.7% of disease variance

Original languageEnglish
Pages (from-to)1377-1384
Number of pages8
JournalDiabetic Medicine
Volume32
Issue number10
DOIs
Publication statusPublished - 1 Oct 2015

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Type 2 Diabetes Mellitus
Single Nucleotide Polymorphism
Population
Alleles
Malaysia
Meta-Analysis
Logistic Models
Odds Ratio

ASJC Scopus subject areas

  • Endocrinology
  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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Characterizing the genetic risk for Type 2 diabetes in a Malaysian multi-ethnic cohort. / Abdullah @ Muda, Noraidatulakma; Abdul Murad, Nor Azian; Attia, J.; Oldmeadow, C.; Mohamad Hanif, Ezanee Azlina; Syafruddin, Saiful Effendi; Abd Jalal, N.; Ismail, N.; Ishak, M.; A. Jamal, A. Rahman; Scott, R. J.; Holliday, E. G.

In: Diabetic Medicine, Vol. 32, No. 10, 01.10.2015, p. 1377-1384.

Research output: Contribution to journalArticle

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AU - Mohamad Hanif, Ezanee Azlina

AU - Syafruddin, Saiful Effendi

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AU - Ismail, N.

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