Open AccessA novel permutation test for case‐only analysis identifies epistatic effects on human longevity in the FOXO gene family
Author(s) -
Tan Qihua,
Soerensen Mette,
Kruse Torben A.,
Christensen Kaare,
Christiansen Lene
Publication year - 2013
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12092
Subject(s) - epistasis , longevity , biology , snp , genetics , gene , single nucleotide polymorphism , phenotype , genotype , computational biology
Summary Genetic interactions or epistasis could make a substantial contribution to variation in human complex traits including longevity. However, detecting epistatic interactions in high dimensional datasets is difficult due to various reasons including multiple testing of correlated tests. We introduce a novel permutation strategy to the case‐only analysis of gene‐by‐gene interaction using multiple SNP s. The method is applied to genes coding for F orkhead box O transcription factors which recently have been associated with human longevity across different populations hypothesizing that epistatic interaction in the regulation and expression of the FOXO gene family could contribute to the human longevity phenotype. Genotype data were collected from 1088 individuals from the D anish 1905 birth cohort aged over 92–93 years with 12 SNP s in the FOXO 1a and 15 SNP s in the FOXO 3a genes. Our analysis detected a joint effect between rs9486902 in FOXO 3a and rs2701858 in FOXO 1a that highly significantly contributes to human longevity ( OR = 3.23, 95% CI : 2.93–3.53) which is consistent in both males and females. Our results were compared with published studies, and importance of our novel method and findings was discussed.