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GWAS meta-analysis highlights the hypothalamic-pituitary-gonadal axis (HPG axis) in the genetic regulation of menstrual cycle length

By Triin Laisk, Viktorija Kukuškina, Duncan Palmer, Samantha Laber, Chia-Yen Chen, Teresa Ferreira, Nilufer Rahmioglu, Krina Zondervan, Christian Becker, Jordan W Smoller, Margaret Lippincott, Andres Salumets, Ingrid Granne, Stephanie Seminara, Benjamin Neale, Reedik Mägi, Cecilia M Lindgren

Posted 30 May 2018
bioRxiv DOI: 10.1101/333708

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. GWAS 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 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.

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