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.
Department of Medical and Molecular Genetics, School of Medicine, Indiana University, Indianapolis, IN, USA. jeejung@iupui.edu
Jeesun
J
Jung
Yiqiang
Y
Zhao
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