- Neuropsychiatric disorders show sex-biased prevalence and presentation, driven by divergent genetic architectures across common and rare variants on autosomes and sex chromosomes.
- Evidence implicates sex chromosome dosage and gonadal hormone signalling as mechanistic drivers, informed by sex-aware functional genomics linking genetics to biological sex differences.
- Translational progress depends on integrating genetic and functional multi-omic datasets within frameworks that incorporate established and emerging principles of sex-differential neurobiology.
Curr Opin Genet Dev. 2026 Sep 22;101:102546. doi: 10.1016/j.gde.2026.102546. Online ahead of print.
ABSTRACT
Sex differences in the prevalence and clinical presentation of neuropsychiatric disorders suggest a corresponding divergence in underlying biological risk mechanisms between males and females. Advances in neuropsychiatric genetics have started to resolve these differences, defining sex-differential genetic architectures and risk loci across common and rare variants on the autosomes and sex chromosomes, with the study of major depressive disorder and neurodevelopmental disorders leading the way. As we look to translate sex-differential genetic signals into mechanistic understanding, emerging evidence highlights roles for sex chromosome dosage and gonadal hormone signaling. Sex-aware functional genomics approaches further provide genome-scale information for aligning genetic risk with these sex-differential biological drivers, baseline sex differences, and sex-differential disorder states. Moving forward, continued progress toward defining the biological basis for sex-biased neuropsychiatric risk will depend on purposeful integration of genetic and functional multi-omic datasets within a framework that incorporates established and developing principles of sex-differential neurobiology.
PMID:42858520 | DOI:10.1016/j.gde.2026.102546
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