Benonisdottir Stefania, Straub Vincent J, Kong Augustine, Mills Melinda C
Leverhulme Centre for Demographic Science, Nuffield Department of Population Health, University of Oxford and Nuffield College, Oxford, UK.
Institute of Physical Science, University of Iceland, Reykjavik, Iceland.
Nat Aging. 2024 Dec;4(12):1745-1759. doi: 10.1038/s43587-024-00733-w. Epub 2024 Dec 13.
Substantial shifts in reproductive behaviors have recently taken place in many high-income countries including earlier age at menarche, advanced age at childbearing, rising childlessness and a lower number of children. As reproduction shifts to later ages, genetic factors may become increasingly important. Although monogenic genetic effects are known, the genetics underlying human reproductive traits are complex, with both causal effects and statistical bias often confounded by socioeconomic factors. Here, we review genome-wide association studies (GWASs) of 44 reproductive traits of both female and male individuals from 2007 to early 2024, examining reproductive behavior, reproductive lifespan and aging, infertility and hormonal concentration. Using the GWAS Catalog as a basis, from 159 relevant studies, we isolate 37 genes that harbor association signals for four or more reproductive traits, more than half of which are linked to rare Mendelian disorders, including ten genes linked to reproductive-related disorders: FSHB, MCM8, DNAH2, WNT4, ESR1, IGSF1, THRB, BRWD1, CYP19A1 and PTPRF. We also review the relationship of reproductive genetics to related health and behavioral traits, aging and longevity and the effect of parental age on offspring outcomes as well as reflecting on limitations, open questions and challenges in this fast-moving field.
最近，许多高收入国家的生殖行为发生了重大变化，包括初潮年龄提前、生育年龄推迟、无子女率上升以及子女数量减少。随着生育年龄推迟，遗传因素可能变得越来越重要。虽然单基因遗传效应是已知的，但人类生殖特征的遗传学很复杂，因果效应和统计偏差常常受到社会经济因素的混淆。在这里，我们回顾了2007年至2024年初关于男性和女性个体44种生殖特征的全基因组关联研究（GWAS），研究了生殖行为、生殖寿命和衰老、不孕不育以及激素浓度。以GWAS目录为基础，我们从159项相关研究中分离出37个基因，这些基因带有四种或更多生殖特征的关联信号，其中一半以上与罕见的孟德尔疾病有关，包括十个与生殖相关疾病有关的基因：FSHB、MCM8、DNAH2、WNT4、ESR1、IGSF1、THRB、BRWD1、CYP19A1和PTPRF。我们还回顾了生殖遗传学与相关健康和行为特征、衰老和长寿的关系，以及父母年龄对后代结局的影响，并反思了这个快速发展领域的局限性、未解决的问题和挑战。
