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Eur J Hum Genet. 2019 Feb 13. doi: 10.1038/s41431-019-0355-z. [Epub ahead of print]

Biological insights into multiple birth: genetic findings from UK Biobank.

Author information

1
Department of Biological Psychology, Amsterdam Public Health Research Institute, Vrije Universiteit, Amsterdam, The Netherlands. h.mbarek@vu.nl.
2
Department of Biological Psychology, Amsterdam Public Health Research Institute, Vrije Universiteit, Amsterdam, The Netherlands.
3
Avera Institute for Human Genetics, Avera McKennan Hospital and University Health Center, Sioux Falls, SD, USA.
4
Department of Psychiatry, Academic Medical Center, Amsterdam, The Netherlands.

Abstract

The tendency to conceive spontaneous dizygotic (DZ) twins is a complex trait with important contributions from both environmental factors and genetic disposition. In earlier work, we identified the first two genes as maternal susceptibility loci for DZ twinning. The aim of this study was to identify genetic variants influencing multiple births and to genetically correlate the findings across a broad range of traits. We performed a genome-wide association study (GWAS) in 8962 participants with Caucasian ancestry from UK Biobank who reported being part of a multiple birth, and 409,591 singleton controls. We replicated the association between FSHB, SMAD3 and twinning in the gene-based (but not SNP-based) test, which had been established in previous genome-wide association analyses in mothers with dizygotic twin offspring. Additionally, we report a novel genetic variant associated with multiple birth, rs428022 at 15q23 (p = 2.84 × 10-8) close to two genes: PIAS1 and SKOR1. Finally, we identified meaningful genetic correlations between being part of a multiple birth and other phenotypes (anthropometric traits, health-related traits, and fertility-related measures). The outcomes of this study provide important new insights into the genetic aetiology of multiple births and fertility, and open up novel directions for fertility and reproduction research.

PMID:
30760885
DOI:
10.1038/s41431-019-0355-z

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