Allelic based gene-gene interaction in case-control studies.
In case-control studies identifying disease susceptibility loci, it has been shown that the interaction caused by multiple single nucleotide polymorphisms (SNPs) within a gene as well as by SNPs at unlinked genes plays an important role in influencing risk of a disease. A novel statistical approach is proposed to detect gene-gene interactions at the allelic level contributing to a disease trait. With a new allelic score inferred from the observed genotypes at two or more unlinked SNPs, we derive a score test from logistic regression and test for association of the allelic scores with a disease trait. Furthermore, F and likelihood ratio tests are derived from Cochran-Armitage regression. By testing for the association, the interaction can be assessed both in cases where the SNP association can be detected and cannot be detected as a main effect in single SNP approach. The analytical power and type I error rates over 6 two-way interaction models are investigated based on the non-centrality parameter approximation of the score test. Simulation studies demonstrate that (1) the power of the score test is asymptotically equivalent to that of the test statistics by the Cochran-Armitage method and (2) the allelic based method provides higher power than two genotypic based methods.
Jung
Jeesun
J
Department of Medical and Molecular Genetics, School of Medicine, Indiana University, Indianapolis, IN, USA. jeejung@iupui.edu
Zhao
Yiqiang
Y
D000465:Algorithms; D000483:Alleles; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics; D016022:Case-Control Studies; D003865:Major Depressive Disorder / Q000235:genetics; D004843:Epistasis, Genetic; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008957:Models, Genetic; D020641:Polymorphism, Single Nucleotide; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics
D019208:Brain-Derived Neurotrophic Factor; D044402:Receptor, Serotonin, 5-HT2A