Genetic evidence that lower circulating FSH levels lengthen menstrual cycle, increase age at menopause and impact female reproductive health
STUDY QUESTION
How does a genetic variant in the FSHB promoter, known to alter FSH levels, impact female reproductive health?
SUMMARY ANSWER
The T allele of the FSHB promoter polymorphism (rs10835638; c.-211G>T) results in longer menstrual cycles and later menopause and, while having detrimental effects on fertility, is protective against endometriosis.
WHAT IS KNOWN ALREADY
The FSHB promoter polymorphism (rs10835638; c.-211G>T) affects levels of FSHB transcription and, as a result, circulating levels of FSH. FSH is required for normal fertility and genetic variants at the FSHB locus are associated with age at menopause and polycystic ovary syndrome (PCOS).
STUDY DESIGN, SIZE, DURATION
We used cross-sectional data from the UK Biobank to look at associations between the FSHB promoter polymorphism and reproductive traits, and performed a genome-wide association study (GWAS) for length of menstrual cycle.
PARTICIPANTS/MATERIALS, SETTING, METHODS
We included white British individuals aged 40–69 years in 2006–2010, in the May 2015 release of genetic data from UK Biobank. We tested the FSH-lowering T allele of the FSHB promoter polymorphism (rs10835638; c.-211G>T) for associations with 29, mainly female, reproductive phenotypes in up to 63 350 women and 56 608 men. We conducted a GWAS in 9534 individuals to identify genetic variants associated with length of menstrual cycle.
MAIN RESULTS AND THE ROLE OF CHANCE
The FSH-lowering T allele of the FSHB promoter...
Source: Human Reproduction - Category: Reproduction Medicine Authors: Ruth, K. S., Beaumont, R. N., Tyrrell, J., Jones, S. E., Tuke, M. A., Yaghootkar, H., Wood, A. R., Freathy, R. M., Weedon, M. N., Frayling, T. M., Murray, A. Tags: Reproductive genetics Source Type: research
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