Gene-gene and gene-environment interactions in meta-analysis of genetic association studies.
Extensive genetic studies have identified a large number of causal genetic variations in many human phenotypes; however, these could not completely explain heritability in complex diseases. Some researchers have proposed that the "missing heritability" may be attributable to gene-gene and gene-environment interactions. Because there are billions of potential interaction combinations, the statistical power of a single study is often ineffective in detecting these interactions. Meta-analysis is a common method of increasing detection power; however, accessing individual data could be difficult. This study presents a simple method that employs aggregated summary values from a "case" group to detect these specific interactions that based on rare disease and independence assumptions. However, these assumptions, particularly the rare disease assumption, may be violated in real situations; therefore, this study further investigated the robustness of our proposed method when it violates the assumptions. In conclusion, we observed that the rare disease assumption is relatively nonessential, whereas the independence assumption is an essential component. Because single nucleotide polymorphisms (SNPs) are often unrelated to environmental factors and SNPs on other chromosomes, researchers should use this method to investigate gene-gene and gene-environment interactions when they are unable to obtain detailed individual patient data.
Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, ROC.
Chin
C
Lin
School of Public Health, National Defense Medical Center, Taipei, Taiwan, ROC.
Chi-Ming
CM
Chu
Math Teachers' Office, Kaohsiung Municipal Girls' Senior High School, Kaohsiung, Taiwan, ROC.
John
J
Lin
School of Public Health, National Defense Medical Center, Taipei, Taiwan, ROC.
Hsin-Yi
HY
Yang
Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, ROC; School of Public Health, National Defense Medical Center, Taipei, Taiwan, ROC.
Sui-Lung
SL
Su
D000465:Algorithms; D002874:Chromosome Mapping; D004843:Epistasis, Genetic; D059647:Gene-Environment Interaction; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008957:Models, Genetic; D020641:Polymorphism, Single Nucleotide