rs10746593 (TLE4): Occupational Status Variant

Key takeaways

• rs10746593 near TLE4 is one of 106 genetic loci linked to occupational status in a UK Biobank GWAS of 273,157 participants.
• The genetics of occupational status overlaps almost completely with educational attainment, pointing to a shared genetic factor for socioeconomic standing broadly.
• Polygenic scores for occupational status explain roughly 2-10% of population-level variation, leaving most variance unexplained by common variants.
• Family environment and other non-genetic factors account for about 62% of how occupational status is passed from parents to children.
• Standard population-based genetic effect estimates may partly reflect indirect parental influences and social sorting, not just direct biological effects.

What the research says A GWAS (genome-wide association study, a method that scans hundreds of thousands of genetic variants across many people to find statistical associations with a trait) of occupational status in 273,157 UK Biobank participants identified 106 independent variants, 8 of which are novel to the genetics of socioeconomic status. Occupational status was measured using three sociologically validated continuous scales: the International Socioeconomic Index (ISEI, which weights education and income through occupation), the Standard International Occupational Prestige Scale (SIOPS, based on public rankings of job social standing), and the Cambridge Social Interaction and Stratification Scale (CAMSIS, based on patterns of social interaction between occupations). Polygenic scores (numerical summaries that combine the estimated effects of many genetic variants into a single number) derived from this study explained 5-10% of variance in occupational status at the population level (incremental R2 = 0.023-0.097 across measures and methods), and genetic correlations (rg, a measure of shared genetic architecture ranging from 0 to 1) with educational attainment reached 0.96-0.97, and with income reached 0.81-0.91.

Reported associations

• Occupational status (ISEI, SIOPS, CAMSIS): rs10746593 near TLE4 is among 106 independent variants associated with occupational status across three sociologically validated scales in a GWAS of 273,157 UK Biobank participants; the available study text does not report a variant-specific effect size for rs10746593.
• Socioeconomic status (shared genetic factor): The genetic architecture underlying occupational status shows near-complete genetic correlation with educational attainment (rg = 0.96-0.97) and strong overlap with income (rg = 0.81-0.91), consistent with a shared latent genetic factor across SES measures.
• Intergenerational transmission of occupational status: Within-family polygenic score predictions are 54-57% weaker than population-based predictions, attributed to indirect parental genetic effects (22-27% attenuation) and assortative mating - the tendency for people with similar genetic profiles to partner together (21-27% attenuation); 62% of occupational status transmission across generations is not explained by common genetic variants.

Evidence quality The GWAS was conducted in the UK Biobank (N = 273,157), a large British population-based cohort, providing substantial statistical power to detect common genetic variants of modest effect. Published in Nature Human Behaviour (2025) by Akimova and colleagues, the study employed three distinct sociologically grounded measures of occupational status rather than a single proxy, strengthening construct validity. However, within-family analyses revealed a 54-57% reduction in polygenic score predictive power compared with population-based estimates. The authors attribute this to indirect parental genetic effects (where a parent's genotype shapes the environment a child grows up in) and assortative mating. This finding indicates that standard population-level effect size estimates for variants including rs10746593 likely overstate the direct biological contribution to occupational outcomes. No variant-specific p-value or effect size for rs10746593 was reported in the provided study text, and the study has no PMID listed in the available metadata.

Lifestyle considerations No lifestyle considerations on file for this variant.