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

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

Research output: Contribution to journalArticle

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 R2 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 R2 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 R2 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 < P < 0.05. Conclusion This study suggests that known genetic risk variants contribute a significant but small amount to overall T2D risk variation in Malaysian population groups. If gene–environment interactions involving common genetic variants exist, they are likely of small effect, requiring substantially larger samples for detection.

Original languageEnglish
Pages (from-to)31-38
Number of pages8
JournalPublic Health
Volume149
DOIs
Publication statusPublished - 1 Aug 2017

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Type 2 Diabetes Mellitus
Area Under Curve
Logistic Models
Malaysia
ROC Curve
Population

Keywords

  • Asian population
  • Epidemiology
  • Gene–environment interaction
  • Population studies
  • Type 2 diabetes

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health

Cite this

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

In: Public Health, Vol. 149, 01.08.2017, p. 31-38.

Research output: Contribution to journalArticle

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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 R2 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 R2 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 R2 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 < P < 0.05. Conclusion This study suggests that known genetic risk variants contribute a significant but small amount to overall T2D risk variation in Malaysian population groups. If gene–environment interactions involving common genetic variants exist, they are likely of small effect, requiring substantially larger samples for detection.",
keywords = "Asian population, Epidemiology, Gene–environment interaction, Population studies, Type 2 diabetes",
author = "{Abdullah @ Muda}, Noraidatulakma and {Abdul Murad}, {Nor Azian} and {Mohamad Hanif}, {Ezanee Azlina} and Syafruddin, {Saiful Effendi} and J. Attia and C. Oldmeadow and Kamaruddin, {M. A.} and {Abd Jalal}, N. and N. Ismail and M. Ishak and {A. Jamal}, {A. Rahman} and Scott, {R. J.} and Holliday, {E. G.}",
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AU - Abdul Murad, Nor Azian

AU - Mohamad Hanif, Ezanee Azlina

AU - Syafruddin, Saiful Effendi

AU - Attia, J.

AU - Oldmeadow, C.

AU - Kamaruddin, M. A.

AU - Abd Jalal, N.

AU - Ismail, N.

AU - Ishak, M.

AU - A. Jamal, A. Rahman

AU - Scott, R. J.

AU - Holliday, E. G.

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N2 - 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 R2 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 R2 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 R2 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 < P < 0.05. Conclusion This study suggests that known genetic risk variants contribute a significant but small amount to overall T2D risk variation in Malaysian population groups. If gene–environment interactions involving common genetic variants exist, they are likely of small effect, requiring substantially larger samples for detection.

AB - 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 R2 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 R2 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 R2 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 < P < 0.05. Conclusion This study suggests that known genetic risk variants contribute a significant but small amount to overall T2D risk variation in Malaysian population groups. If gene–environment interactions involving common genetic variants exist, they are likely of small effect, requiring substantially larger samples for detection.

KW - Asian population

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KW - Gene–environment interaction

KW - Population studies

KW - Type 2 diabetes

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