Fertility is affected by mechanisms that influence reproductive biology and human behaviour, a new study has shown.
In the largest study to date identifying genetic determinants of the number of children an individual may have, researchers hope their discoveries will lead to therapeutic targets for reproductive diseases.
Led by teams at the Universities of Cambridge, Oxford, Groningen and Pennsylvania, the study also discovered part of the human genome that has been influenced by natural selection for thousands of years.
Their findings, published in Nature Human Behaviour, show how fertility is affected by diverse biological mechanisms, which contribute to variations in fertility, and directly affect puberty timing, sex hormone levels, endometriosis and age at menopause. There were also links to behaviours such as risk taking.
Professor Melinda Mills, director of Oxford’s Leverhulme Centre for Demographic Science, said: “This study is of interest to understanding changes in human reproduction over longer periods of time, reproductive biology and potential links to infertility.
“It also empirically tests one of the most gripping and fundamental questions asked by scientists across many disciplines and decades: Is there evidence of ongoing natural selection in humans and, if so, what is it and how does it operate?”
The researchers analysed data from 785,604 individuals of European ancestry, including people in the UK Biobank study, to identify 43 regions of the genome containing genetic variants associated with reproductive success (the number of children ever born to an individual).
They found variations in the gene ARHGAP27 were associated with having more children, but also with a shorter lifetime window of fertility; their analysis also suggested a novel role for the red hair colour gene, melanocortin 1 receptor (MC1R) in reproductive biology.
Professor John Perry, of the MRC Epidemiology Unit at the University of Cambridge, said: “This study is the largest of its kind and has highlighted new biology that we anticipate will help identify novel therapeutic targets for reproductive diseases such as infertility. It will also help us better understand the biological mechanisms that link reproductive health to broader health outcomes in men and women.”
When they integrated their findings from modern genomes with ancient genome data, the team identified the regions FADS1 and FADS2 are involved in synthesising specific fats that are important for health.
They believe these have been important in helping people in Europe to adapt to an agricultural diet and that these genes still affect fertility today, suggesting the adaptation may be ongoing.
Dr Iain Mathieson from the Department of Genetics, University of Pennsylvania, said: “Independent evidence shows that the FADS region has been under selection in Europe for thousands of years. It represents the clearest example of a genetic variant with evidence of both historical and ongoing natural selection, though the reason for selection remains unclear.”
Mathieson I, Day FR, Barban N et al. Genome-wide analysis identifies genetic effects on reproductive success and ongoing natural selection at the FADS locus. Nature Human Behaviour 2 March 2023
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