Identifying genetic determinants of reproductive success may highlight mechanisms underlying fertility and also identify alleles under present-day selection. Using data in 785,604 individuals of European ancestry, we identify 43 genomic loci associated with either number of children ever born (NEB) or childlessness. These loci span diverse aspects of reproductive biology across the life course, including puberty timing, age at first birth, sex hormone regulation and age at menopause. Missense alleles in ARHGAP27 were associated with increased NEB but reduced reproductive lifespan, suggesting a trade-off between reproductive ageing and intensity. As NEB is one component of evolutionary fitness, our identified associations indicate loci under present-day natural selection. Accordingly, we find that NEB-increasing alleles have increased in frequency over the past two generations. Furthermore, integration with data from ancient selection scans identifies a unique example of an allele - FADS1/2 gene locus - that has been under selection for thousands of years and remains under selection today. Collectively, our findings demonstrate that diverse biological mechanisms contribute to reproductive success, implicating both neuro-endocrine and behavioural influences.

中文翻译：

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全基因组分析确定了FADS基因座对生殖成功和正在进行的自然选择的遗传影响。

鉴定生殖成功的遗传决定因素可能会突出显示生育力的潜在机制，并且还可以鉴定当前选择下的等位基因。使用785,604名欧洲血统的个体的数据，我们确定了43个基因组位点，这些基因位点与成年子女（NEB）或无子女人数相关。这些基因座跨越了整个生命过程中生殖生物学的各个方面，包括青春期时机，初生年龄，性激素调节和绝经年龄。ARHGAP27中的错义等位基因与NEB增加但生殖寿命缩短有关，表明在生殖衰老和强度之间进行权衡。由于NEB是进化适应性的一个组成部分，因此我们确定的关联性表明了当今自然选择下的基因座。因此，我们发现，在过去的两代中，NEB增加的等位基因频率增加。此外，与来自古代选择扫描的数据相结合，鉴定了一个等位基因的独特实例-FADS1 / 2基因位点-已经进行了数千年的选择，至今仍在选择中。总的来说，我们的研究结果表明，多种生物学机制有助于生殖成功，牵涉神经内分泌和行为影响。