Navigation Links
Claims of sex-related differences in genetic association studies often not properly validated

A review of previous research suggests that prominent claims of sex differences of gene-disease associations are often insufficiently documented and validated, according to an article in the August 22/29 issue of JAMA.

In the human genome era, for many common diseases, published research has often considered that some common gene variants may have different effects in men vs. women. Many diseases or traits with strong genetic backgrounds have different prevalence in the two sexes and many studies try to determine differences in risks between men and women, according to background information in the article.

Nikolaos A. Patsopoulos, M.D., of the University of Ioannina School of Medicine, Ioannina, Greece and colleagues evaluated a large sample of prominently claimed sex differences for genetic effects and whether these claims were methodologically strong or were made based on selected and/or suboptimal analyses and with insufficient or questionable documentation. From a database search the authors identified 77 articles with 432 sex-difference claims.

Of these claims, 286 (66.2 percent) sex comparisons were reported as being decided a priori (in advance of the study) and 68 (15.7 percent) were acknowledged to be post hoc (after the study) analyses; in the other 78 (18.1 percent), the analysis plan was unclear. Appropriate documentation of gene-sex interaction was recorded in 55 claims (12.7 percent); documentation was insufficient for 303 claims and spurious (not valid) for the other 74. Data for reanalysis of claims were available for 188 comparisons. Of these, 83 (44.1 percent) were nominally statistically significant, and more than half of them (n = 44) failed to reach nominal statistical significance of a certain level. Of 60 claims with seemingly the best internal validity, only one was consistently replicated in at least two other studies.

the majority of these claims were insufficiently documented or spurious, and reporting of statistical interaction tests was rare, the authors write.

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.


Contact: John P. A. Ioannidis
JAMA and Archives Journals

Related biology news :

1. UCLA Study Shows One-Third of Drug Ads in Medical Journals Do Not Contain References Supporting Medical Claims
2. Variation in womens X chromosomes may explain differences among individuals, between sexes
3. Big differences in duplicated DNA distinguish chimp and human genomes
4. Comparison of Cocaine, Methamphetamine ‘Highs?Finds Differences
5. Identical twins may have more differences than meet the eye
6. Study outlines genetic differences between potential pandemic influenza strains
7. Brain differences could explain why males and females experience pain relief differently
8. Most human-chimp differences due to gene regulation ?not genes
9. Albatross study shows regional differences in ocean contamination
10. Viral genetic differences are possible key to HIV dementia
11. New brain-chemistry differences found in depressed women
Post Your Comments:
(Date:11/4/2015)... 4, 2015 --> ... published by Transparency Market Research "Home Security Solutions Market - ... 2015 - 2022", the global home security solutions market is expected ... 2022. The market is estimated to expand at a ... to 2022. Rising security needs among customers at homes, ...
(Date:10/29/2015)... 2015 Daon, a global leader in mobile ... a new version of its IdentityX Platform , ... America have already installed IdentityX v4.0 and ... FIDO UAF certified server component as an ... FIDO features. These customers include some of the largest ...
(Date:10/29/2015)... , Oct. 29, 2015 Today, ... announced a partnership with 2XU, a global leader ... deliver a smart hat with advanced bio-sensing technology. ... other athletes to monitor key biometrics to improve ... strategic partnership, the two companies will bring together the ...
Breaking Biology News(10 mins):
(Date:11/24/2015)... Nov. 24, 2015 Cepheid (NASDAQ: CPHD ... at the following conference, and invited investors to participate ...      Tuesday, December 1, 2015 at 11.00 a.m. ...      Tuesday, December 1, 2015 at 11.00 a.m. ... New York, NY      Tuesday, December ...
(Date:11/24/2015)... ... 2015 , ... International Society for Pharmaceutical Engineering (ISPE) closed ... events for pharmaceutical manufacturing: 2015 Annual Meeting. The conference took place in Philadelphia, ... number of attendees in more than a decade. , “The 2015 Annual ...
(Date:11/24/2015)... ... November 24, 2015 , ... This fall, global software solutions leader SAP ... states to develop and pitch their BIG ideas to improve health and wellness in ... for votes to win the title of SAP's Teen Innovator, an all-expenses paid trip ...
(Date:11/24/2015)... , Nov. 24, 2015  Tikcro Technologies Ltd. (OTCQB: TIKRF) today ... December 29, 2015 at 11:00 a.m. Israel time, ... Tower, 98 Yigal Allon Street, 36 th Floor, Tel ... Eric Paneth and Izhak Tamir to the Board ... Skaliter as external directors; , approval of an amendment to certain ...
Breaking Biology Technology: