Sex-specific associations between education-related genetic factors and fertility extend beyond educational attainment

Population fertility patterns are closely linked to socioeconomic inequality, with educational attainment (EA) being a key predictor of completed fertility. While EA is partially heritable, the extent to which EA-associated genetic variation relates to fertility independently of education remains unclear, particularly outside Western European and North American populations. Using data from [~]40,000 women and [~]10,000 men in the Estonian Biobank, we examine sex-specific associations between EA polygenic scores (PGSEA) and completed fertility. We extend prior work by distinguishing cognitive and non-cognitive EA components, accounting for age at first pregnancy (AFP), and applying within-family analyses to assess the role of direct genetic effects. Among women, PGSEA is negatively associated with fertility, with a significantly stronger association for the non-cognitive than the cognitive EA polygenic score. The association between PGSEAand fertility is moderated by EA and changes sign across AFP strata, from negative among women with earlier AFP to positive among those with later AFP. Importantly, this association is not attenuated in within-family models, consistent with a predominant role of direct genetic effects. Among men, associations are weak or slightly positive and stable across education groups. Overall, EA-related genetic variation is associated with fertility through pathways that appear largely independent of educational attainment, suggesting that shared genetic influences operate through multiple mechanisms that differ by sex and reproductive timing. SignificanceEducational attainment is closely linked to completed fertility, yet the mechanisms behind this relationship remain not fully understood. Using a population-based cohort from Estonia, we show that genetic variants associated with education relate to fertility in markedly different ways for women and men and that these associations cannot be explained by education level alone. Differences between cognitive and non-cognitive education-related genetic components further point to multiple life-course pathways linking genetics and reproduction. Family-based analyses suggest that these associations are largely consistent with direct genetic effects and not driven by correlated family environments. Together, our findings suggest that education-related genetic variation shapes fertility through multiple sex-specific and life-course-dependent pathways, rather than acting solely through educational attainment.