Proteomic Sex Index from 51,000 people quantifies molecular sex beyond XX/XY chromosomes
andganna · x · 2026-10-27
Andrea Ganna's team introduces the Proteomic Sex Index (PSI), built on 31 blood proteins across 6 cohorts and >51,000 people, measuring how far one's proteome deviates from chromosomal-sex-typical profiles.
Key findings:
- Males with female-typical proteomes had shorter grip strength but lower severe COVID-19 risk (OR=0.59); PSI also linked to future hypothyroidism (male-typical females: renal failure risk)
- Klinefelter syndrome (XXY) individuals showed markedly elevated PSI (OR=13.7)
- PSI shifts during gender-affirming hormone therapy beyond what testosterone/estradiol explain
- PSI is partially heritable, with sex-biased cis-pQTLs and causal links to sex-specific disease risk
Trained via XGBoost on 43K UK Biobank participants, validated in MESA, FinnGen, Biobank Japan and more. A continuous, individualized measure for studying within-sex molecular variation and health.
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