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Efficient Strategy for Detecting Gene × Gene Joint Action and Its Application in Schizophrenia
Author(s) -
Won Sungho,
Kwon MinSeok,
Mattheisen Manuel,
Park Suyeon,
Park Changsoon,
Kihara Daisuke,
Cichon Sven,
Ophoff Roel,
Nöthen Markus M.,
Rietschel Marcella,
Baur Max,
Uitterlinden Andre G.,
Hofmann A.,
Lange Christoph
Publication year - 2014
Publication title -
genetic epidemiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.301
H-Index - 98
eISSN - 1098-2272
pISSN - 0741-0395
DOI - 10.1002/gepi.21779
Subject(s) - linkage disequilibrium , genetic association , genome wide association study , disequilibrium , genetics , gene , biology , computational biology , computer science , allele , single nucleotide polymorphism , haplotype , genotype , medicine , ophthalmology
We propose a new approach to detect gene × gene joint action in genome‐wide association studies (GWASs) for case‐control designs. This approach offers an exhaustive search for all two‐way joint action (including, as a special case, single gene action) that is computationally feasible at the genome‐wide level and has reasonable statistical power under most genetic models. We found that the presence of any gene × gene joint action may imply differences in three types of genetic components: the minor allele frequencies and the amounts of Hardy‐Weinberg disequilibrium may differ between cases and controls, and between the two genetic loci the degree of linkage disequilibrium may differ between cases and controls. Using Fisher's method, it is possible to combine the different sources of genetic information in an overall test for detecting gene × gene joint action. The proposed statistical analysis is efficient and its simplicity makes it applicable to GWASs. In the current study, we applied the proposed approach to a GWAS on schizophrenia and found several potential gene × gene interactions. Our application illustrates the practical advantage of the proposed method.