rs10793933 (ASS1-FUBP3): Cardiometabolic GWAS Locus

Key takeaways

• rs10793933, at the ASS1-FUBP3 locus, has been analyzed in large-scale UK Biobank genome-wide association studies with samples ranging from approximately 162,000 to 405,000 participants.
• A sex-specific GWAS of polyphenotypic cardiometabolic sex-scores - composite trait measures weighting individual traits by sex-difference effect sizes - in over 300,000 UK Biobank participants found that genes at sex-score-associated loci were enriched for expression in brain and cervical tissues, while genes at loci found via simpler unweighted analyses were enriched in the liver.
• Genetic correlation analyses linked sex-score and sum-score GWAS signals to cardiometabolic, immune, and psychiatric conditions.
• A large-scale GWAS using the Quickdraws method (a scalable Bayesian approach with a spike-and-slab prior) identified 4.97% more quantitative trait associations and 3.25% more binary trait associations than the REGENIE comparison method in approximately 405,000 UK Biobank participants.
• Specific effect sizes and p-values for this variant individually are not reported in the provided study text.

What the research says A sex-specific GWAS analyzed polyphenotypic cardiometabolic sex-scores (composite scores that weight individual traits by their respective sex-difference effect sizes to capture within-sex degrees of femaleness or maleness) and unweighted sum-scores in approximately 161,906 females and 141,980 males from the UK Biobank; genes at sex-score-associated loci were enriched for expression in the cervix and across brain tissues, and genetic correlation analyses implicated these signals in cardiometabolic, immune, and psychiatric disorders (Vosberg et al., 2023, Scientific Reports). A separate methodological study applied the Quickdraws algorithm - a mixed-model GWAS approach using a spike-and-slab prior (a statistical model allowing for both large-effect and small-effect genetic variants) and stochastic variational inference (a computationally efficient Bayesian estimation technique) - to 79 quantitative and 50 binary traits in approximately 405,088 UK Biobank individuals, identifying 4.97% and 3.25% more associations than REGENIE and 22.71% and 7.07% more than FastGWA for quantitative and binary traits respectively, with replicated gains also observed in Biobank Japan and FinnGen cohorts (Loya et al., 2025, Nature Genetics).

Reported associations

• Polyphenotypic cardiometabolic sex-differentiated composites: The sex-score GWAS (Vosberg et al., 2023) analyzed composite traits aggregating anthropometric and metabolic phenotypes - including waist-to-hip ratio, standing height, and trunk fat percentage - weighted by sex-difference effect sizes; loci identified via sex-score analyses showed enrichment for genes expressed in brain and cervical tissues, with the strongest brain-related enrichment appearing among male-dominant genes.
• Cardiometabolic, immune, and psychiatric disorder correlates: Genetic correlation analyses in the same study found that both sex-score and sum-score GWAS signals showed associations with cardiometabolic, immune, and psychiatric conditions; specific odds ratios or effect sizes for this locus are not reported in the provided text.
• Broad quantitative and binary phenotype landscape: The Quickdraws GWAS (Loya et al., 2025) covered 79 quantitative and 50 binary complex traits in approximately 405,088 UK Biobank participants, with identified associations validated in Biobank Japan and FinnGen; per-variant statistics for this locus are not reported in the provided study excerpts.

Evidence quality Both studies drew on the UK Biobank, providing sample sizes from approximately 303,886 sex-stratified participants (Vosberg et al., 2023) to approximately 405,088 in the Quickdraws analysis (Loya et al., 2025). The sex-score study used sex-stratified analyses, which can uncover sex-specific effects missed by combined-sex approaches, but the polyphenotypic sex-score construct is novel and its clinical relevance is not yet fully established; the study also included a sum-score control condition to distinguish sex-differentiated signals from simple trait aggregation effects. The Quickdraws study validated power gains via replication in Biobank Japan and FinnGen, lending confidence that its identified associations are not UK Biobank-specific artifacts. Neither provided study text reports per-variant statistics such as odds ratios, beta coefficients, or p-values for rs10793933 individually; the specific effect magnitude and significance at this locus cannot be assessed from the available excerpts. Independent replication of any association specific to this variant has not been described in the provided material, and findings should be considered preliminary pending such replication.

Lifestyle considerations No lifestyle considerations on file for this variant.