We discovered genetic variants influencing fertility

According to the World Health Organisation, around 17.5% of the adult population – roughly 1 in 6 – experience infertility, with an urgent need for research in this area. Data4Science Founder Professor Melinda Mills and Professor at the University of Oxford, led a team of researchers from across the global to produce multiple ground-breaking studies to understand the genetic, biological and environmental causes and predictors of fertility.

In 2016, Mills led the first ever genetic epidemiological study on human reproductive behaviour including information from over 250,000 men and women, published in the prestigious journal Nature Genetics. Due to the fact that many couples are waiting to older ages to start families, genetic and biological factors are increasingly important.

“One day it may be possible to use this information so doctors can answer the important question: “How late can you wait?” based on the DNA variants,” said Melinda Mills. “It is important to put this into perspective, however, since having a child still strongly depends on many social and environmental factors that will always play a bigger role in whether or when we have babies.”

In 2021, Mills extended this with a much larger study in Nature Human Behaviour, of over a half a million individuals related to reproductive milestones of the timing of when people have children. Mills noted: “Our study has discovered hundreds additional genetic markers that shape this most fundamental part of our lives and have the potential for deeper understanding of infertility, later life disease and longevity.’”

The genetic signals were driven by social factors and the environment but also by reproductive biology, with findings related to follicle-stimulating hormone, implantation, infertility, and spermatid differentiation.

Mills adds “We already knew that childhood socioeconomic circumstances or level of education were important predictors of the timing of reproduction. But we were intrigued to find literally not only hundreds of new genetic variants, but also uncover a relationship with substance abuse, personality traits such as openness and self-control, ADHD and even predictive of some diseases and longevity .”

In 2023 expanded research further in Nature Human Behaviour, demonstrating that fertility is affected by diverse biological mechanisms, which contribute to variations in fertility, and directly affect puberty timing, sex hormone levels (such as testosterone), endometriosis and age at menopause and links to behaviours such as risk taking. With her team, Mills worked with researchers across the world to combine data from 785,604 individuals and identified 43 regions of the genome containing genetic variants associated with number of children ever born.

The team then integrated their findings from modern genomes with ancient genome data, allowing them to identify a region of the genome that has been under selection for thousands of years, and remains under selection today. The genes in this region – FADS1 and FADS2 – are involved in synthesising specific fats that are important for health and seem to have been important in helping people in Europe to adapt to an agricultural diet. The observation that these genes still affect fertility today suggests that this adaptation may be ongoing!

Researchers from around the world want to continue to engage in this kind of research to help couples who have difficulty conceiving a child and to understand fertility. We need people who voluntarily participate in research and contribute multiple types of data to produce even more novel and ground-breaking scientific discoveries.

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