Systematic review reveals multiple sexually antagonistic polymorphisms affecting human disease and complex traits

Area of Science:

• Evolutionary biology
• Human genetics
• Disease risk

Background:

• Sexually antagonistic (SA) alleles are hypothesized to influence sex differences in disease susceptibility.
• These alleles may be protected from selection if they confer benefits in one sex, despite risks in the other.
• Previous research suggested a lack of SA alleles in humans, potentially due to terminology differences.

Purpose of the Study:

• To investigate the prevalence of SA polymorphisms in humans.
• To determine if discipline-specific terminology obscures the identification of SA alleles.
• To bridge communication gaps between evolutionary biology and biomedicine.

Main Methods:

• A two-stage literature review was conducted.
• Search terms were drawn from both evolutionary biology and biomedical fields.
• Genes with sex-opposite effects on disease risk or severity were identified.

Main Results:

• No studies were found using only evolutionary biology search terms.
• A review using biomedical terms identified 51 genes with sex-opposite effects.
• Of these, 22 genes showed opposing effects (risk in one sex, protection in the other); those with net positive effects were more frequent.

Conclusions:

• SA alleles are likely present in humans but are not recognized as such due to varied terminology.
• Interdisciplinary communication is crucial for accurate identification and study of SA genetic variants.
• This finding has implications for understanding sex differences in disease etiology and evolution.