Combining multiple genetic risk scores with social environmental factors in explaining childlessness

Using GWAS meta-analysis we previously found genes for number of children ever born (NEB) and age at first birth (AFB). Based on these results, we created polygenic risk scores (PGS) and found that genes related to AFB have an... [ view full abstract ]

Using GWAS meta-analysis we previously found genes for number of children ever born (NEB) and age at first birth (AFB). Based on these results, we created polygenic risk scores (PGS) and found that genes related to AFB have an impact on childlessness in a Swedish sample. In the current study we extend these findings by examining the relative importance of, and interplay between, the genetic and social environmental influences in predicting childlessness. We take into account multiple PGS for fertility-related traits in addition to modelling social environmental factors using data from men and women from the Health and Retirement Study (N=12,205). We created PGS for NEB and AFB and will do the same for endometriosis, age at menopause, polycystic ovary syndrome, azoospermia, oligozoospermia and testicular dysgenesis syndrome. We further include the influence of marital status, educational and occupational behavior and birth cohort. Initial results show a positive relationship between the AFB PGS and childlessness: the odds of remaining childless are around 1.18 times higher for women and 1.14 times higher for men with a 1 SD higher score on the AFB PGS. About half of this effect is mediated by education, meaning that these genes influence educational attainment which affects childlessness. In line with twin heritability studies suggesting higher heritability of AFB in more recent cohorts, we find that the PGS also have a stronger effect on childlessness in more recent birth cohorts (p=0.0117) and is stronger for women with low and relatively high educational attainment (p=0.0089 & p=0.002). In the next analytical steps we will add the individual and combined effects of the PGS for the other fertility-related traits on childlessness to our models and results will be presented at the conference.