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The case-only study, proposed as a design specifically for assessing departure from multiplicative gene-environment and gene-gene interactions, is of considerable potential value but there are concerns about its validity. The objective of this study was to evaluate the extent and sources of bias in the case-only design by means of a systematic review and meta-regression analysis.

Bias in the case-only design applied to studies of gene-environment and gene-gene interaction: a systematic review and meta-analysis