Analysis of the interaction effect of 48 SNPs and obesity on type 2 diabetes in Chinese Hans

Jia Liu; Lu Wang; Yun Qian; Qian Shen; Hai Chen; Hongxia Ma; Juncheng Dai; Chong Shen; Guangfu Jin; Zhibin Hu; Hongbing Shen

doi:10.1136/bmjdrc-2020-001638

Analysis of the interaction effect of 48 SNPs and obesity on type 2 diabetes in Chinese Hans

BMJ Open Diabetes Res Care. 2020 Nov;8(2):e001638. doi: 10.1136/bmjdrc-2020-001638.

Authors

Jia Liu¹, Lu Wang¹, Yun Qian², Qian Shen¹, Hai Chen¹, Hongxia Ma³, Juncheng Dai³, Chong Shen³, Guangfu Jin³, Zhibin Hu³, Hongbing Shen³

Affiliations

¹ Department of Health Promotion & Chronic Non-Communicable Disease Control, Wuxi Center for Disease Control and Prevention, Wuxi, China.
² Department of Health Promotion & Chronic Non-Communicable Disease Control, Wuxi Center for Disease Control and Prevention, Wuxi, China wxqianyun111@sina.com.
³ Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China.

Abstract

Introduction: Both environmental and genetic factors contribute to type 2 diabetes (T2D) risk. Dozens of T2D susceptibility loci have been identified by genome-wide association study. However, these loci account for only a small fraction of the familial T2D risk. We hypothesized that the gene-obesity interaction may contribute to the missing heritability.

Research design and method: Forty-eight T2D-associated variants were genotyped using the TaqMan OpenArray Genotyping System and iPLEX Sequenom MassARRAY platform in two separate studies. Obesity was defined according to multiple indexes (body mass index (BMI), waist circumference and waist-hip ratio). Multiplicative interactions were tested using general logistic regression to assess the gene-obesity interaction effect on T2D risk among a total of 6206 Chinese Hans.

Results: After adjusting for the main effects of genes and obesity, as well as covariates (age, sex, smoking and alcohol consumption status), robust multiplicative interaction effects were observed between rs10811661 in CDKN2A/CDKN2B and multiple obesity indices (p ranged from 0.001 to 0.043 for BMI, waist circumference and waist-hip ratio). Obese individuals with the TT genotype had a drastically higher risk of T2D than normal weight individuals without the risk allele (OR=17.58, p<0.001). There were no significant differences between subgroups in the stratification analysis. Plausible biological explanations were established using a public database. However, there were no significant interaction effects between the other 47 single nucleotide polymorphism (SNPs) and obesity.

Conclusion: Our findings indicated that the CDKN2A/CDKN2B gene-obesity interaction significantly increases T2D risk in Chinese Hans. The interaction effect identified in our study may help to explain some of the missing heritability in the context of T2D susceptibility. In addition, the interaction effect may play a role in the precise prevention of T2D in Chinese individuals.

Keywords: diabetes mellitus; genetics; obesity; type 2.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

China / epidemiology
Diabetes Mellitus, Type 2* / epidemiology
Diabetes Mellitus, Type 2* / genetics
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Obesity* / epidemiology
Obesity* / genetics
Polymorphism, Single Nucleotide*