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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.

Original publication




Journal article


Hum Mol Genet

Publication Date





4323 - 4332


Female, Gene Expression Regulation, Genetic Predisposition to Disease, Genome-Wide Association Study, Gonadotropin-Releasing Hormone, Humans, Hypothalamo-Hypophyseal System, Insulin-Like Growth Factor II, Menstrual Cycle, Ovary, Polymorphism, Single Nucleotide, Promoter Regions, Genetic, Protein Precursors, Receptors, Cytoplasmic and Nuclear, Reproduction