NEW YORK – A genetic study by investigators at the University of Bristol has failed to detect a causal role for testosterone in socioeconomic position, such as income or employment status, despite previously reported ties between high testosterone levels and enhanced socioeconomic status in men.
"Many factors contribute to socioeconomic success, but our results suggest that a person's natural level of testosterone isn't one of them. If we want to explain inequalities in where people end up in life, we need to look in other places," senior author Amanda Hughes, an epidemiologist and population health sciences researcher at the University of Bristol, said in an email.
As they reported in Science Advances on Wednesday, the researchers first brought together genotyping profiles and measurements of bioavailable testosterone in the blood of hundreds of thousands of UK Biobank participants, including 104,632 post-menopausal women, more than 36,200 pre-menopausal women, and 148,248 men, for a sex-stratified genome-wide association study focused on finding variants linked to testosterone levels.
After identifying polygenic contributors to testosterone levels in the men, pre-menopausal women, and post-menopausal women, the team used Mendelian randomization analysis to search for potential ties between testosterone-related genetic variants and everything from socioeconomic status — income, educational attainment, neighborhood-level deprivation, and the like — to risk-taking behaviors, smoking history, self-reported health status, and body mass index.
"We found little evidence that testosterone affected socioeconomic position, health, or risk-taking," the authors reported, noting that "it is unlikely that testosterone meaningfully affects these outcomes in men and women."
While "traditional" analytic approaches such as multivariable-adjusted modeling did point to potential ties between testosterone levels and individuals' socioeconomic positions, particularly for the male participants, Hughes noted that the investigators saw little to no testosterone association with socioeconomic factors when they performed genetics-informed Mendelian analyses, which were expected to be less influenced by confounding factors or reverse causation.
In the pre- and post-menopausal women, multivariable-adjusted models pointed to lower socioeconomic status, income, or health levels for those with higher levels of bioavailable testosterone. Again, though, the Mendelian randomization data suggested that bioavailable testosterone levels did not appear to have a causal influence on the socioeconomic factors considered.
"Differences between Mendelian randomization and multivariable-adjusted estimates suggest that previously reported associations with socioeconomic position and health may be due to residual confounding or reverse causation," she and her co-authors wrote.
From these and other results, the authors speculated that some socioeconomic factors may influence testosterone levels rather than the reverse, perhaps accounting for the multivariable-adjusted analysis results, though they warned that individuals participating in the UK Biobank project are believed to be somewhat healthier and more socioeconomically privileged than individuals in the broader population.
"Participants of the UK Biobank tend to be wealthier and healthier than the country as a whole, and this non-representativeness may bias estimates of effect sizes, including from genetic models," the authors wrote. Even so, they reported, "application of genetic causal inference methods in a large UK sample suggests that many previously reported associations of testosterone with socioeconomic outcomes, health, and risk-taking are unlikely to be causal."