Study finds new genetic loci associated with menopause onset

Monday, January 23, 2012

An international team of researchers from the Boston University Schools of Public Health and Medicine and other institutions has uncovered 13 genetic loci, linked to immune function and DNA repair, that are factors in the age of onset of menopause.

Menopause -- the cessation of reproductive function of the ovaries -- is a major hormonal change that affects most women when they are in their early 50s. Most prior studies of the age of onset of menopause have focused on genes from the estrogen-production pathway or vascular components.

In the new study, published online Jan. 22 in Nature Genetics, a research team led by Kathryn Lunetta, professor of biostatistics at the BU School of Public Health, and Joanne Murabito, associate professor of medicine at the BU School of Medicine, identified 13 novel loci associated with menopause onset, while confirming four previously established loci. Most of the 17 loci are associated with genes related to DNA damage repair or auto-immune disease; others are linked to hormonal regulation.

"Our findings demonstrate the role of genes which regulate DNA repair and immune function, as well as genes affecting neuroendocrine pathways of ovarian function in regulating age at menopause, indicating the process of aging is involved in both somatic and germ line aging" the authors said.

Lunetta said the new findings "bring us closer to understanding the genetic basis for the timing of menopause. They may also provide clues to the genetic basis of early onset or premature menopause and reduced fertility.

"We hope that as a better understanding of the biologic effects of these menopause-related variants are uncovered, we will gain new insights into the connections between menopause and cardiovascular disease, breast cancer, osteoporosis, and other traits related to aging, and that this will provide avenues for prevention and treatment of these conditions," she said.

According to Murabito, director of the research clinic at the Framingham Heart Study, "It will be important to determine if a genetic variant that directly influences age at menopause also increases risk for later life health conditions, such as breast cancer."

The authors said they expected further research to identify "a substantial number of additional common variants" that impact age of menopause, and that many of them will be located in genes identified in their study. The study examined more than 50,000 women of European descent who had experienced menopause between the ages of 40 and 60.

The research team noted that a large-scale study of menopause onset in African-American women is underway, which will help to determine whether the genetic variations that affect menopause onset in African-American women are similar or substantially different for women of primarily European descent.

Besides Lunetta and Murabito, senior authors on the study include: Anna Murray, a senior lecturer in genetics at the Peninsula Medical School in Exeter (UK); and Jenny A. Visser, a scientist at Erasmus Medical Center in Rotterdam (Netherlands).

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Boston University Medical Center: http://www.bmc.org

Thanks to Boston University Medical Center for this article.

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