Augmented GWAS of Dizygotic Twinning in a New Sample of Mothers of DZ Twins From Australia and New Zealand Highlights CLYBL as a New Gene Influencing DZT

Abstract

Dizygotic twinning (DZT) is an important marker of female fertility. The Twinning Genetics Consortium (TGC) recently reported the largest genomewide association meta-analysis (GWAMA) of DZT, identifying six genomewide significant loci and a seventh supported by functional evidence, in 8265 mothers of spontaneous DZ twins (MoDZTs) and 264,567 European-ancestry controls. To identify additional loci, we continued recruitment of MoDZTs in Australia and New Zealand (ANZ). Here, we report a GWAS of a new ANZ2026 sample (1598 MoDZTs and 5317 controls) and a GWAMA combining this sample with the previously reported ANZ2023 dataset. A new locus near CLYBL on chromosome 13 was tentatively identified. Because CLYBL is associated with vitamin B12 levels linked to fertility, it represents a plausible candidate. However, despite a 51% increase in ANZ cases, only one additional locus emerged, supporting the hypothesis that DZT is an oligogenic rather than highly polygenic trait. Meta-analysis with the TGC2024, the largest existing GWAS of DZT, strengthened signals at several loci, including HLA-G, while weakening others, such as ZFPM1 .