How Genetic Variations Influence Fertility, Family and Longevity

A study led by researchers from the Leverhulme Centre for Demographic Science at the University of Oxford and the University of Iceland examines how genetic variation can explain differences in reproductive health and longevity. The study provides the most comprehensive overview to date of genetic discoveries in men and women associated with reproductive traits, and offers new insights into how our DNA affects childbearing, the timing of menopause, and even longevity.

Genes at the Center of Reproduction

Using the GWAS Catalog, an online database of genome-wide association studies (GWAS), researchers identified 159 genetic studies and 37 key genes associated with reproductive traits such as age at first birth, time of menopause, and hormones such as follicle-stimulating hormone (FSH) and testosterone. These findings suggest that genetic factors play a significant role in overall health and also influence fertility.

In particular, one gene, FSHB (follicle-stimulating hormone subunit beta), was associated with 11 different reproductive outcomes. This gene helps regulate the onset of menstruation and the onset of menopause, highlighting its role in both reproductive health and aging. The research also revealed links between these reproductive genes and rare genetic disorders, showing how DNA affects both fertility and overall health.

Senior lead author Professor Melinda Mills, Director of the Leverhulme Centre for Demographic Science and the Demographic Science Unit at Oxford Population Health, said: “As more and more people are postponing parenthood to a later age, it is important to understand the genetic factors that influence an individual’s reproductive health and fertility window. The study brings together research on the genetics of reproduction to uncover shared genes across traits and gain insights beyond fertility, which are inherently linked to health, body mass index (BMI) and obesity, hormone-sensitive cancers, and even psychiatric and behavioral traits. By consolidating this research, researchers can provide a clearer picture of how genetic factors influence reproductive health. This is essential for the advancement of healthcare, particularly with regard to infertility and reproductive aging.

Longevity, Cancer, Obesity Risk and Reproductive Traits

The study examined the links between reproductive genes and longevity and found that genes such as ESR1 (estrogen receptor 1) are associated with both reproductive traits and cancer risk. For example, earlier age of puberty or later age of menopause can increase the risk of hormone-sensitive cancers such as breast cancer, but these same traits are also associated with longer life expectancy. The FTO gene (Fat Mass and Obesity Associated gene) – which has already been found to be strongly linked to BMI, obesity risk and type 2 diabetes – has also been linked to several different reproductive traits. Understanding these genetic links is crucial as more and more people choose to delay starting a family, further intertwining reproductive health and aging.

Male Fertility

While previous research has focused on women’s reproductive health, the study examines what is known about the genetics of male fertility. Genes like DNAH2 have been shown to play a role in both testosterone levels and sperm function, making them crucial to men’s reproductive health. Co-author Vincent Straub, a doctoral researcher at the Leverhulme Centre for Demographic Science and Oxford Population Health, said: “Men’s reproductive health is crucial to overall fertility but often understudied. By studying the genetics of male infertility, we can gain new insights and uncover potential treatment options for people experiencing reproductive challenges.”

Genetics Across Generations

The study examined how genetic changes affect future generations. With age, parents accumulate de novo mutations – new, spontaneous genetic changes that can be passed on to their children. These mutations can have a significant impact on the health and development of offspring, as senior co-author Professor Augustine Kong has previously discovered. This large-scale study provides important insights into how our genes influence reproductive health, fertility and longevity, and lays the foundation for more personalized approaches to healthcare that could improve outcomes for individuals and families across generations.