It seems that assertions of sex differences of gene disease associations are frequently poorly documented and validated, according to a review of previous research reported in the
Research has frequently indicated that some common gene variants may affect men and women differently. The report states that several studies seek to determine variation in risk between the sexes for diseases or traits with strong genetic backgrounds.
Nikolaos A. Patsopoulos, M.D., University of Ioannina School of Medicine, Ioannina, Greece and team examined a large number of prominently claimed sex differences for genetic effects. They wanted to see whether these claims were methodologically sound, or whether they were based on selected or suboptimal analyses and with deficient or questionable documentation. They looked at 77 articles which included 432 sex-difference claims.
Of these claims, the researchers found that:
— 66.22% (286) sex comparisons were reported as being decided before the study analyses
— 15.7% (68) were decided after the study analyses
— 18.1% (78) of the analysis plans were unclear
— 12.7% (55) of claims had appropriate documentation of gene-sex interaction recorded
— 303 claims had insufficient documentation
— 74 claims were spurious
The researchers found that data for reanalysis of claims were available for 188 comparisons, 44.1 (83) of which were nominally statistically significant.
The writers wrote “The majority of these claims were insufficiently documented or spurious, and reporting of statistical interaction tests was rare. We hope that our empirical evaluation will help sensitize clinicians, geneticists, epidemiologists, and statisticians who are pursuing subgroup analyses by sex or other subgroups on genetic associations. The pursuit of gene-sex interactions should not be necessarily abandoned. Ideally, sex differences should be based on a priori, clearly defined, and adequately powered subgroups. Post hoc, discovery-based analyses are also of interest, but their post hoc character should be clearly stated in the manuscript. Both a priori and post hoc claims should be documented by interaction tests and proper consideration of the multiplicity of comparisons involved. Even then, results should be explained with caution and should be replicated by several other studies before being accepted as likely modifications of genetic or other risks.”
Written by: Christian Nordqvist