Approved Research

Cross-sectional study of genome-wide associations with fertility

Lay summary

Human fertility is tracked at the population level, often by survey participants reporting whether they have biological children, and the number of such children. Population averages of fertility are often reported at the national level, and as individuals' social influences and plans for a family are not collected, we model the entire range of statuses (as a biological mother or father of one or more children) among a nation-scale population. Our project is a genome-wide association study with reproduction in the adult UK population. The project differs from the existing genome-wide association study, which associated each genotype with number of biological children in male and female cohorts, without regard to age. In the set of UK Biobank participants, who cover a cross-section of time, reproductive outcomes are modeled at a continuous rate, in cohorts grouped by both sex and age. For both sexes and at each age interval (a cohort), we fit average number of new children, as well as the entire range of outcomes at this particular age. The variability of outcomes in each cohort is driven by individual choice, and the average and spread of outcomes differ in each cohort. Significant genotype associations with a perturbed reproductive rate (in any cohort) might be driven by changes in fertility, driving the number of children lower for one genotype. The association tests will generate new hypotheses for genes that could interfere with, or protect, fertility. In public health, gene expression may be impacted by environmental factors, and may also be applied as a drug target. The former considerations can be part of evidence-based reproductive health care, while we would also like to make fertility extension possible by suggesting potential targets in pharmacology.