Claims of Sex Differences: An Empirical Assessment in Genetic Associations

Abstract

Context Many studies try to probe for differences in risks between men and women, and this is a major challenge in the expanding literature of associations between genetic variants and common diseases or traits. Objective To evaluate whether prominently claimed sex differences for genetic effects have sufficient internal and external validity. Data sources We searched PubMed through July 6, 2007, for genetic association studies claiming sex-related differences in the articles' titles. Titles and abstracts and, if necessary, the full text of the article were assessed for eligibility. Study selection Two hundred fifteen articles were retrieved by the search. We considered eligible all retrieved association studies that claimed different genetic effects across sexes of 1 or more gene variants for any human disease or phenotype. We considered both biallelic and multiallelic markers (including haplotypes) and both binary and continuous phenotypes and traits. We excluded non-English-language studies; studies evaluating only 1 sex; studies in which sex was treated only as an independent predictor of disease; studies that did not address any association of the investigated genetic variant with a disease or trait; studies not involving humans; and studies in which the authors did not claim any sex difference. Data extraction Two evaluators independently extracted data with a third evaluator arbitrating their discrepancies. Data evaluation included whether analyses were stated to have…