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
{"title":"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。","authors":"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","doi":"10.1007/s10815-025-03515-4","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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<sub>g</sub> = - 0.698) and PCOS (r<sub>g</sub> = - 0.278), and endometriosis (r<sub>g</sub> = 0.279).</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":15246,"journal":{"name":"Journal of Assisted Reproduction and Genetics","volume":" ","pages":""},"PeriodicalIF":3.2000,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Polygenic scores for dizygotic twinning: insights into the genetic architecture of female fertility.\",\"authors\":\"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\",\"doi\":\"10.1007/s10815-025-03515-4\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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<sub>g</sub> = - 0.698) and PCOS (r<sub>g</sub> = - 0.278), and endometriosis (r<sub>g</sub> = 0.279).</p><p><strong>Conclusions: </strong>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.</p>\",\"PeriodicalId\":15246,\"journal\":{\"name\":\"Journal of Assisted Reproduction and Genetics\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.2000,\"publicationDate\":\"2025-05-27\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Assisted Reproduction and Genetics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s10815-025-03515-4\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"GENETICS & HEREDITY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Assisted Reproduction and Genetics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s10815-025-03515-4","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
Polygenic scores for dizygotic twinning: insights into the genetic architecture of female fertility.
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 (rg = - 0.698) and PCOS (rg = - 0.278), and endometriosis (rg = 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.
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.
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