Gene Studies of Male-Female Differences Often Flawed

TUESDAY Aug. 21, 2007 -- Claims of male-female differences in how genes affect disease often lack proper documentation or validation, experts report in the Aug. 22/29 issue of the Journal of the American Medical Association.

A team of researchers in Greece analyzed 77 studies that contained 432 gender-difference claims.

They found that 286 (66.2 percent) of these claims were decided in advance of the study, and 68 (15.7 percent) were drawn from post-study analyses. The analysis plan was unclear in 78 (18.1 percent) of the studies.

The review also found that appropriate documentation of gene-sex interaction was recorded in just 55 claims (12.7 percent), while there was insufficient documentation for 303 claims and invalid documentation for 74 claims.

Dr. Nikolaos A. Patsopoulos of the University of Ioannina School of Medicine and colleagues concluded that "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 researchers said.

In many cases, the proof of any real gender-based gene differences was weak. For example, data for re-analysis of gender-difference claims were available for 188 comparisons, the research team said. Of those, 83 (44.1 percent) were nominally statistically significant, and more than half of those (44) failed to reach nominal statistical significance of a certain level, the review authors said.

Of 60 claims with seemingly "the best internal validity," only one was consistently replicated in at least two other studies.

Studies of gene-sex interactions shouldn't be abandoned but should be conducted using more rigorous standards and documentation, the Greek team said. In addition, the results of such studies should be replicated by several other studies before the findings are accepted as valid, they wrote.

More information

The U.S. Food and Drug Administration has more about gender and disease.

Posted: August 2007


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