SynthesisPsychological medicine2026
Unravelling sex differences in the genetic architecture of anxiety.
Synthesis in Psychological medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 2 papers.
What it found
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Who cites it
2 citing papers in PubMed.
- Uncovering the Role of Biological Sex in the Divergent Genetic Profiles of Early and Late-Diagnosed Autism.Research square · 2026Article
- Sex differences in LDL-C genetic architecture and statin efficacy in All of Us.medRxiv : the preprint server for health sciences · 2026Article
Corrections and comments
- Erratum issued
Authors and funding
10 authors.
Funding
Abstract
backgroundAnxiety disorders show striking sex differences in prevalence, symptoms, and clinical characteristics, shaping how they manifest and are experienced.
methodsHere, we report the first sex-specific meta-analysis of genome-wide association studies (GWAS) of anxiety, leveraging two of the largest biobank datasets, UK Biobank and All of Us, comprising 85,042 female cases with 196,789 controls and 36,732 male cases with 136,924 controls. Functional annotation, sex-specific polygenic scores (PGS), and genetic correlations were performed to assess genetic differences and functional implications.
resultsIn females, 21 lead SNPs were significantly associated with anxiety, compared to five in males. Although the genetic correlation between sexes was high, it was significantly different from one, indicating partially distinct genetic architectures. In addition, both the SNP-based observed and liability-scale heritabilities (assuming a 2:1 female-to-male prevalence ratio) were significantly higher in females. Gene-based tests and functional prioritization identified different genes associated with anxiety in females and males. Moreover, genetic correlation analyses revealed stronger associations of female anxiety with attention-deficit/hyperactivity disorder (ADHD) and body mass index (BMI), whereas male anxiety showed stronger correlations with waist-hip-ratio-adjusted BMI.
conclusionsWhile the overall genetic architecture of anxiety is largely shared, our findings reveal distinct sex-specific genetic associations and correlations, highlighting the value of analyzing the sexes separately to uncover genetic signals that may be masked in sex-combined samples.
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