Assessing effects of disease genes and gene-environment interactions: the case-spouse design and the counterfactual-control analysis.
BACKGROUND
Assessing joint genetic and environmental contributions to disease risk is the central issue in many genetic epidemiological studies. To characterise the effects of a gene, the case-control study may suffer from the problem of population stratification bias. For a late onset disease, recruiting control subjects into case-parents and case-sibling studies may be difficult.


METHODS
Two novel approaches to analysing case-spouse data are introduced: the 1:1 case-counterfactual-control analysis (genotype swapping between the case and their spouse) and the 1:5 case-counterfactual-controls analysis (allele swapping).


RESULTS
Both can be implemented using statistical packages that allow matched analysis (the conditional logistic regression) to yield valid estimates of the genotype relative risk, the gene-environment interaction parameter, the gene-sex interaction parameter, and the gene-environment-sex three factor interaction parameter (if desired), if certain assumptions are fulfilled.


CONCLUSIONS
Because of the ease in recruiting subjects, and in collecting and analysing data, this approach makes a convenient tool for gene characterisation.
Lee
Wen-Chung
WC
Graduate Institute of Epidemiology, College of Public Health, National Taiwan University, Taipei. wenchung@ha.mc.ntu.edu.tw
Chang
Chin-Hao
CH
D015982:Bias; D004781:Environmental Exposure / Q000009:adverse effects*; D004812:Epidemiologic Methods; D020022:Genetic Predisposition to Disease / Q000209:etiology*; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics*; D012307:Risk Factors; D018454:Spouses