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Hum Mol Genet. 2018 Dec 15;27(24):4323-4332. doi: 10.1093/hmg/ddy317.

Large-scale meta-analysis highlights the hypothalamic-pituitary-gonadal axis in the genetic regulation of menstrual cycle length.

Author information

1
Department of Obstetrics and Gynecology, Institute of Clinical Medicine, University of Tartu, Tartu, Estonia.
2
Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Estonia.
3
Competence Centre on Health Technologies, Tartu, Estonia.
4
Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
5
Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.
6
Big Data Institute, Li Ka Shing Center for Health for Health Information and Discovery, Oxford University, Oxford, UK.
7
Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
8
Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.
9
Broad Institute of MIT and Harvard, Boston, Massachusetts, USA.
10
Oxford Endometriosis CaRe Centre, Nuffield Department of Women's and Reproductive Health, University of Oxford, UK.
11
Harvard Reproductive Sciences Center and Reproductive Endocrine Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.
12
Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
13
Department of Biomedicine, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia.
14
Nuffield Department of Women's and Reproductive Health, University of Oxford, UK.
15
Program in Medical and Population Genetics, Broad Institute, Boston, MA, USA.

Abstract

The normal menstrual cycle requires a delicate interplay between the hypothalamus, pituitary and ovary. Therefore, its length is an important indicator of female reproductive health. Menstrual cycle length has been shown to be partially controlled by genetic factors, especially in the follicle-stimulating hormone beta-subunit (FSHB) locus. A genome-wide association study meta-analysis of menstrual cycle length in 44 871 women of European ancestry confirmed the previously observed association with the FSHB locus and identified four additional novel signals in, or near, the GNRH1, PGR, NR5A2 and INS-IGF2 genes. These findings not only confirm the role of the hypothalamic-pituitary-gonadal axis in the genetic regulation of menstrual cycle length but also highlight potential novel local regulatory mechanisms, such as those mediated by IGF2.

PMID:
30202859
PMCID:
PMC6276838
DOI:
10.1093/hmg/ddy317
[Indexed for MEDLINE]
Free PMC Article

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