title: Investigating statistical epistasis in complex disorders.
abstract: The missing heritability exhibited by late-onset Alzheimer's disease is unexplained and has been partly attributed to epistatic interaction. Methods available to explore this are often based on logistic regression and allow for determination of deviation from an expected outcome as a result of statistical epistasis. Three such methodologies including Synergy Factor and the PLINK modules, -epistasis and -fast-epistasis, were applied to study an epistatic interaction between interleukin-6 and interleukin-10. The models analyzed consisted of two synergistic interactions (SF ≈ 4.2 and 1.6) and two antagonistic interactions (SF ≈ 0.9 and 0.6). As with any statistical test, power to detect association is paramount; and most studies will be underpowered for the task. However, the availability of large sample sizes through genome-wide association studies make it feasible to examine approaches for determining epistatic interactions. This study documents the sample sizes needed to achieve a statistically significant outcome from each of the methods examined and discusses the limitations/advantages of the chosen approaches.
authors.affiliation: Human Genetics, School of Molecular Medical Sciences, Queens Medical Centre, University of Nottingham, Nottingham, UK.
authors.forename: James C
authors.initials: JC
authors.lastname: Turton
authors.forename: James
authors.initials: J
authors.lastname: Bullock
authors.forename: Christopher
authors.initials: C
authors.lastname: Medway
authors.forename: Hui
authors.initials: H
authors.lastname: Shi
authors.forename: Kristelle
authors.initials: K
authors.lastname: Brown
authors.forename: Olivia
authors.initials: O
authors.lastname: Belbin
authors.forename: Noor
authors.initials: N
authors.lastname: Kalsheker
authors.forename: Minerva M
authors.initials: MM
authors.lastname: Carrasquillo
authors.forename: Dennis W
authors.initials: DW
authors.lastname: Dickson
authors.forename: Neill R
authors.initials: NR
authors.lastname: Graff-Radford
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Petersen
authors.forename: Steven G
authors.initials: SG
authors.lastname: Younkin
authors.forename: Kevin
authors.initials: K
authors.lastname: Morgan
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000453:epidemiology / Q000235:genetics*; D016001:Confidence Intervals; D004843:Epistasis, Genetic / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D015233:Models, Statistical; D020641:Polymorphism, Single Nucleotide; D018401:Sample Size; D012984:Software
chemical_list: D015850:Interleukin-6; D016753:Interleukin-10