Predicting type 2 diabetes using genetic and environmental risk factors in a multi-ethnic Malaysian cohort

Abdullah N 1 , Abdul Murad NA 2 , Mohd Haniff EA 2 , Syafruddin SE 2 , Attia J 3 , Oldmeadow C 3 Show all authors , Kamaruddin MA 2 , Abd Jalal N 2 , Ismail N 2 , Ishak M 2 , Jamal R 4 , Scott RJ 5 , Holliday EG 6

Affiliations 

  • 1 School of Biomedical Sciences and Pharmacy, Faculty of Health, University of Newcastle, Newcastle, NSW, Australia; UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
  • 2 UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
  • 3 Clinical Research Design, IT and Statistical Support (CReDITSS) Unit, Hunter Medical Research Institute, Newcastle, NSW, Australia; Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, Faculty of Health, University of Newcastle, Newcastle, NSW, Australia
  • 4 UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia. Electronic address: rahmanj@ppukm.ukm.edu.my
  • 5 School of Biomedical Sciences and Pharmacy, Faculty of Health, University of Newcastle, Newcastle, NSW, Australia; Hunter Area Pathology Service, John Hunter Hospital, Newcastle, NSW, Australia
  • 6 Clinical Research Design, IT and Statistical Support (CReDITSS) Unit, Hunter Medical Research Institute, Newcastle, NSW, Australia; Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, Faculty of Health, University of Newcastle, Newcastle, NSW, Australia. Electronic address: elizabeth.holliday@hmri.org.au
Public Health, 2017 Aug;149:31-38.
PMID: 28528225 DOI: 10.1016/j.puhe.2017.04.003

Abstract

OBJECTIVE: Malaysia has a high and rising prevalence of type 2 diabetes (T2D). While environmental (non-genetic) risk factors for the disease are well established, the role of genetic variations and gene-environment interactions remain understudied in this population. This study aimed to estimate the relative contributions of environmental and genetic risk factors to T2D in Malaysia and also to assess evidence for gene-environment interactions that may explain additional risk variation.
STUDY DESIGN: This was a case-control study including 1604 Malays, 1654 Chinese and 1728 Indians from the Malaysian Cohort Project.
METHODS: The proportion of T2D risk variance explained by known genetic and environmental factors was assessed by fitting multivariable logistic regression models and evaluating McFadden's pseudo R(2) and the area under the receiver-operating characteristic curve (AUC). Models with and without the genetic risk score (GRS) were compared using the log likelihood ratio Chi-squared test and AUCs. Multiplicative interaction between genetic and environmental risk factors was assessed via logistic regression within and across ancestral groups. Interactions were assessed for the GRS and its 62 constituent variants.
RESULTS: The models including environmental risk factors only had pseudo R(2) values of 16.5-28.3% and AUC of 0.75-0.83. Incorporating a genetic score aggregating 62 T2D-associated risk variants significantly increased the model fit (likelihood ratio P-value of 2.50 × 10(-4)-4.83 × 10(-12)) and increased the pseudo R(2) by about 1-2% and AUC by 1-3%. None of the gene-environment interactions reached significance after multiple testing adjustment, either for the GRS or individual variants. For individual variants, 33 out of 310 tested associations showed nominal statistical significance with 0.001 

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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