Scientists have found new gene variants linked with the age at which females experience their first menstrual period and the onset of menopause, which can even help in preventing breast and endometrial cancer and osteoporosis, and cardiovascular disease.
In the collaborative study led by Harvard School of Public Health (HSPH), the researchers have identified 10 genetic variants in two chromosomal regions associated with age at menarche (the first menstrual period), and 13 genetic variants in four chromosomal regions associated with age at natural menopause.
Menarche and natural menopause are two important physiological events in a woman’s life.
The researchers explained that an early onset of menarche and later menopause are well-established risk factors for the development of breast cancer and endometrial cancer.
On the other hand, early menopause increases risk of osteoporosis and cardiovascular disease.
Previous studies have suggested both menarche and menopause may be partially under genetic control.
And thus, to identify common genetic variants influencing these states, the researchers analysed more than 317,000 gene variants in a total of 17,438 women from the Nurses’ Health Study (NHS) and the Women’s Genome Health Study (WGHS) based at BWH.
“At these newly identified loci, fine mapping or sequencing might lead to identification of the causal variants, and thus expand our knowledge of the underlying physiology and biological regulation of these traits. Insights into the genetic factors influencing the timing of menarche and natural menopause might shed light on normal reproductive function and the prevention of the diseases associated with these two traits,” Nature magazine quoted lead author Chunyan He, a doctoral student at HSPH, as saying.
Daniel Chasman, Director of Computational Biology in the Center for Cardiovascular Disease Prevention at Brigham and Women’s Hospital, said:
“The collaboration of the WGHS and the NHS represents a great example of how large cohorts with genome-wide data can complement each other. While only one locus reached near genome-wide significance in the NHS alone, the meta-analysis of combined data had much more statistical power and revealed a total of two loci for timing of menarche and four for timing of menopause.”
Chasman, also an assistant professor at Harvard Medical School, added: “Of the loci for timing of menopause, three were already strong but not proven candidates in the NHS; these loci reached genome-wide significance in the WGHS alone, supplementing the meta-analysis by a second mode of validation through replication. The remaining locus, for timing of menopause, would not have been identified, even as a candidate, without the joint power of these two cohorts working together.
“Future collaborations will hopefully continue to leverage the combined power of the two cohorts for association studies directed at other clinical characteristics.”
Titled ‘Genome-wide association studies identify loci associated with age at menarche and at natural menopause’, the study has been published online in Nature Genetics.