Discussing gene-gene interaction: warning--translating equations to English may result in jabberwocky.
Interest in mapping susceptibility alleles for complex diseases, which do not follow a classic single-gene segregation pattern, has driven interest in methods that account for, or use information from one locus when mapping another. Our discussion group examined methods related to epistasis or gene x gene interaction. The goal of modeling gene x gene interaction varied across groups; some papers tried to detect gene x gene interaction while others tried to exploit it to map genes. Most of the 10 papers summarized here applied newly created or newly modified statistical methods related to gene x gene interaction, while two groups primarily examined computational issues. As is often the case, comparisons are complicated by little overlap in the data used across the papers, and further complicated by the fact that the available data may not have been ideal for some gene x gene interaction methods. However, the main difficulty in comparing and contrasting methods across the papers is the lack of a consistent statistical definition of gene x gene interaction. But despite these issues, two clear trends emerged across the analyses: First, the methods for quantitative trait gene x gene interaction appeared to perform very well, even in families initially ascertained as affected sib pairs; and second, dichotomous trait gene x gene interaction methods failed to produce consistent results. The difficulty of using (primarily) affected sib pair data in a gene x gene interaction analysis is explored.
Bartlett
Christopher W
CW
Center for Quantitative and Computational Biology and Department of Pediatrics, College of Medicine, The Ohio State University, Columbus, OH, USA. bartletc@ccri.net
Vieland
Veronica J
VJ
Bartlett
Jacquelaine
J
Bell
Jordana T
JT
Bhattacharjee
Samsiddhi
S
Clerget-Darpoux
Françoise
F
Bush
William S
WS
Edwards
Todd L
TL
Gao
Guimin
G
Halder
Indrani
I
Huang
Yungui
Y
Kotti
Salma
S
Larkin
Emma K
EK
Li
Hua
H
Motsinger
Alison A
AA
Mukhopadhyay
Nandita
N
Namkung
Junghyun
J
Park
Taesung
T
Ritchie
Marylyn D
MD
Stein
Catherine M
CM
Zhou
Ji-Yuan
JY
D000483:Alleles; D016022:Case-Control Studies; D004843:Epistasis, Genetic; D008040:Genetic Linkage; D006801:Humans; D008957:Models, Genetic; D020641:Polymorphism, Single Nucleotide