Genome-Wide Gene-Environment Interaction Analysis Using Set-Based Association Tests

• Main Authors: Wan-Yu Lin, Ching-Chieh Huang, Yu-Li Liu, Shih-Jen Tsai, Po-Hsiu Kuo
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2019-01-01
• Series: Frontiers in Genetics
• Subjects: diastolic blood pressure; systolic blood pressure; hypertension; gene-alcohol interaction; Taiwan Biobank; multiple testing correction
• Online Access: https://www.frontiersin.org/article/10.3389/fgene.2018.00715/full

The identification of gene-environment interactions (G × E) may eventually guide health-related choices and medical interventions for complex diseases. More powerful methods must be developed to identify G × E. The “adaptive combination of Bayes factors method” (ADABF) has been proposed as a powerful genome-wide polygenic approach to detect G × E. In this work, we evaluate its performance when serving as a gene-based G × E test. We compare ADABF with six tests including the “Set-Based gene-EnviRonment InterAction test” (SBERIA), “gene-environment set association test” (GESAT), etc. With extensive simulations, SBERIA and ADABF are found to be more powerful than other G × E tests. However, SBERIA suffers from a power loss when 50% SNP main effects are in the same direction with the SNP × E interaction effects while 50% are in the opposite direction. We further applied these seven G × E methods to the Taiwan Biobank data to explore gene× alcohol interactions on blood pressure levels. The ADAMTS7P1 gene at chromosome 15q25.2 was detected to interact with alcohol consumption on diastolic blood pressure (p = 9.5 × 10−7, according to the GESAT test). At this gene, the P-values provided by other six tests all reached the suggestive significance level (p < 5 × 10−5). Regarding the computation time required for a genome-wide G × E analysis, SBERIA is the fastest method, followed by ADABF. Considering the validity, power performance, robustness, and computation time, ADABF is recommended for genome-wide G × E analyses.