Polygenic scores for dizygotic twinning: insights into the genetic architecture of female fertility.

IF 3.2 3区医学 Q2 GENETICS & HEREDITY

Journal of Assisted Reproduction and Genetics Pub Date : 2025-05-27 DOI:10.1007/s10815-025-03515-4

Nikki Hubers, Christian M Page, René Pool, Hamdi Mbarek, Nils Lambalk, Velja Mijatovic, Lannie Ligthart, Jenny van Dongen, Siri Håberg, Elizabeth C Corfield, Jeffrey J Beck, Erik A Ehli, Nicholas G Martin, Gonneke Willemsen, Jennifer R Harris, Jouke-Jan Hottenga, Dorret I Boomsma

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引用次数: 0

Abstract

Purpose: Natural dizygotic twinning (DZT) results from hyper-ovulation and is an indicator of female fertility. However, some traits linked to DZ twinning are also associated with infertility. We examined the relationship between DZT and female (in)fertility using recent GWAS findings.

Methods: We investigated the genetic architecture of DZT and compared polygenic scores (PGS) for DZT between mothers of naturally conceived DZ twin pregnancies and mothers who required fertility treatments (MAR) in the Netherlands Twin Register (NTR) and the Norwegian Mother, Father, and Child Cohort Study (MoBa). We also calculated genetic correlations between DZT and seven fertility related traits.

Results: DZT has a low polygenicity, with only 0.20% of SNPs estimated to have a nonzero effect. The DZT PGS explains 1.6% of variance in DZT liability, and we observe an odds ratio of 2.29 between the first and the tenth PGS deciles. The DZT PGS distinguishes between mothers of naturally conceived pregnancies and mothers who received MAR and is associated with a shorter time to pregnancy in mothers of singletons. The lowest PGSs were observed for mothers who received hormonal ovulation induction, indicating maternal fertility issues. DZT showed genetic correlations with anovulatory infertility (r_g = - 0.698) and PCOS (r_g = - 0.278), and endometriosis (r_g = 0.279).

Conclusions: Female fertility appears to exists on a genetic spectrum, with anovulation/infertility at one end and DZT at the other. Results suggest that the DZT PGS can be of added value to evaluate female fertility and be incorporated in clinical practice in the future.

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异卵双胞胎的多基因评分：对女性生育能力遗传结构的洞察。

目的：自然异卵双胞胎（DZT）是高排卵的结果，是女性生育能力的指标。然而，与DZ双胞胎有关的一些特征也与不孕有关。我们利用最近的GWAS研究结果检验了DZT与女性生育能力之间的关系。方法：我们研究了DZT的遗传结构，并比较了荷兰双胞胎登记（NTR）和挪威母亲、父亲和儿童队列研究（MoBa）中自然受孕的DZ双胞胎母亲和需要生育治疗（MAR）的母亲之间DZT的多基因评分（PGS）。我们还计算了DZT与7个育性相关性状的遗传相关。结果：DZT具有低多基因性，估计只有0.20%的snp具有非零效应。DZT PGS解释了DZT负债中1.6%的方差，我们观察到第一个和第十个PGS十分位数之间的比值比为2.29。DZT PGS区分了自然怀孕的母亲和接受MAR的母亲，并且与单胎母亲的怀孕时间较短有关。在接受激素促排卵的母亲中观察到最低的pgs，这表明母亲有生育问题。DZT与无排卵性不孕症（rg = - 0.698）、PCOS （rg = - 0.278）和子宫内膜异位症（rg = 0.279）存在遗传相关性。结论：女性生育能力似乎存在于遗传谱上，一端是无排卵/不育，另一端是DZT。结果表明，DZT PGS在评价女性生育能力方面具有一定的价值，可用于临床实践。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Assisted Reproduction and Genetics 医学-妇产科学

CiteScore

5.70

自引率

9.70%

发文量

286

审稿时长

1 months

期刊介绍： The Journal of Assisted Reproduction and Genetics publishes cellular, molecular, genetic, and epigenetic discoveries advancing our understanding of the biology and underlying mechanisms from gametogenesis to offspring health. Special emphasis is placed on the practice and evolution of assisted reproduction technologies (ARTs) with reference to the diagnosis and management of diseases affecting fertility. Our goal is to educate our readership in the translation of basic and clinical discoveries made from human or relevant animal models to the safe and efficacious practice of human ARTs. The scientific rigor and ethical standards embraced by the JARG editorial team ensures a broad international base of expertise guiding the marriage of contemporary clinical research paradigms with basic science discovery. JARG publishes original papers, minireviews, case reports, and opinion pieces often combined into special topic issues that will educate clinicians and scientists with interests in the mechanisms of human development that bear on the treatment of infertility and emerging innovations in human ARTs. The guiding principles of male and female reproductive health impacting pre- and post-conceptional viability and developmental potential are emphasized within the purview of human reproductive health in current and future generations of our species. The journal is published in cooperation with the American Society for Reproductive Medicine, an organization of more than 8,000 physicians, researchers, nurses, technicians and other professionals dedicated to advancing knowledge and expertise in reproductive biology.