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

## TL;DR

This study explores the genetic factors behind dizygotic twinning and how they relate to female fertility and infertility.

## Contribution

The study introduces a polygenic score for dizygotic twinning and links it to fertility traits and treatment outcomes.

## Key findings

- Dizygotic twinning has low polygenicity, with only 0.20% of SNPs having a nonzero effect.
- The DZT polygenic score explains 1.6% of variance in DZT liability and distinguishes between natural and medically assisted pregnancies.
- DZT shows strong genetic correlations with anovulatory infertility and PCOS, suggesting a genetic spectrum of fertility.

## Abstract

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.

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.

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).

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.

The online version contains supplementary material available at 10.1007/s10815-025-03515-4.