MCM8 rs16991615: Understanding Reproductive Aging Associations
The rs16991615 variant is a specific change in the DNA sequence of the MCM8 gene. It has been identified in large-scale studies as being associated with the timing of natural menopause and markers of ovarian reserve.
What each genotype means
Typical natural menopause timing
You carry two copies of the reference G allele at this location in the MCM8 gene. Population-based genetic studies associate this genotype with a typical timing for natural menopause and standard ovarian reserve decline. Because overall evidence for this specific variant is limited, individual reproductive lifespan remains strongly shaped by broader genetic and clinical factors.
Carried by approximately 85% to 86% of people of European ancestry and at even higher frequencies in African and East Asian populations.
Slightly earlier natural menopause
You carry one copy of the A minor allele associated with accelerated oocyte depletion and earlier ovarian aging. Genome-wide association studies observed that individuals with one A allele experience natural menopause roughly one year earlier on average compared to non-carriers. This finding reflects a modest statistical association in large population cohorts rather than a definitive prediction for any individual.
Carried by roughly 1 in 7 to 1 in 8 people of European ancestry, and less frequently in African and East Asian populations.
Earlier average age at menopause
You carry two copies of the minor A allele linked to faster depletion of the ovarian follicle pool. Research indicates that carrying two copies of this variant is statistically associated with reaching natural menopause nearly two years earlier on average than non-carriers. While this genotype indicates a potential shift in reproductive lifespan, overall research evidence for this variant remains limited and does not diagnose early menopause.
Carried by less than 1% of individuals of European ancestry and exceptionally rare in African and East Asian populations.
What is rs16991615?
The variant rs16991615 is a single nucleotide polymorphism (SNP) located within the MCM8 gene on chromosome 20. In genetic terms, this is a missense variant, meaning the change in the DNA sequence results in a different amino acid being incorporated into the protein structure. Specifically, this variant is often described as a p.Glu341Lys substitution. Because it is located within a coding region of the gene, researchers have investigated whether this change alters the function of the resulting protein. This SNP has been a frequent subject of genome-wide association studies (GWAS), which look for statistical correlations between specific genetic markers and physical traits across large groups of people. It is important to note that while this variant is statistically linked to reproductive traits, it is just one of many genetic and environmental factors that influence human biology.
The Role of the MCM8 Gene
The MCM8 gene provides instructions for making a protein that is part of the minichromosome maintenance (MCM) complex. This protein plays a critical role in DNA repair, specifically in a process called homologous recombination, which is essential for maintaining genomic stability during cell division. In the context of reproductive health, the MCM8 protein is expressed in the ovaries and is thought to be involved in the development and maintenance of ovarian follicles—the structures that contain immature eggs. Research in both animal models and human studies suggests that the MCM8 protein helps ensure that DNA damage is repaired correctly during the formation and maturation of oocytes. When this repair process is impaired, it may lead to a faster depletion of the ovarian reserve, which is the total pool of eggs available throughout a woman's reproductive lifespan.
Research and Evidence Strength
The association between rs16991615 and the age of natural menopause has been replicated across multiple studies, particularly in populations of European ancestry. Statistical analysis from these studies suggests that the minor allele is associated with a modest delay in the age of natural menopause, typically estimated at around one year per copy of the allele. Additionally, this variant has been linked to levels of anti-Müllerian hormone (AMH), a common clinical marker used to estimate the size of the remaining ovarian reserve. While the statistical evidence for these associations is strong at a population level, the evidence is considered limited in terms of clinical predictability for an individual. Furthermore, the association is not universal; some studies have found that the link is less consistent or absent in other ancestral groups, highlighting the complexity of genetic influences on reproductive aging.
Population Frequency
The frequency of the rs16991615 variant varies significantly depending on ancestral background. In European populations, the minor allele frequency is typically reported between 0.07 and 0.08. In contrast, the frequency is notably lower in African and East Asian populations. These differences in frequency, combined with variations in the surrounding genetic architecture (linkage disequilibrium), mean that the statistical associations observed in one population may not be directly applicable to others. Researchers emphasize that these population-specific differences are a crucial consideration when interpreting genetic data, as they underscore the importance of diversity in genomic research to ensure that findings are robust and broadly representative.
Interpreting Your Genetic Information
It is important to understand that rs16991615 is a marker of statistical association, not a diagnostic tool. Having a specific genotype at this location does not determine the exact age at which an individual will reach menopause, nor does it provide a definitive assessment of current fertility. Reproductive health is influenced by a complex interplay of genetics, lifestyle, environment, and overall health history. This information should not be used to make medical decisions or to predict personal reproductive outcomes. If you have questions about your reproductive health, fertility, or the timing of menopause, the most appropriate course of action is to consult with a qualified healthcare provider or a reproductive endocrinologist. They can provide personalized guidance based on your clinical history and current health status, rather than relying on individual genetic variants.
How common is this variant?
The minor allele frequency is approximately 0.07-0.08 in European populations, while it is significantly lower in African and East Asian ancestries.
Frequently asked questions
Can this SNP predict when I will go through menopause?
No, this SNP cannot predict the exact age of menopause. While it is statistically associated with the timing of menopause at a population level, individual outcomes are influenced by many other genetic and environmental factors.
Is rs16991615 a cause of infertility?
No, this variant is not considered a direct cause of infertility. It is a marker associated with the rate of ovarian reserve depletion, but it does not determine an individual's ability to conceive.
Should I get tested for this variant?
There is no clinical recommendation to test for this variant. It is primarily used in research settings to understand the biological mechanisms of reproductive aging and does not provide actionable clinical information for individuals.
Does this variant affect my risk of ovarian cancer?
Current research focuses on the association between this variant and the timing of menopause and ovarian reserve. There is no established evidence that this specific SNP significantly alters the risk of ovarian cancer.
Sources & further reading
Educational information only, last refreshed 10/19/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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Intergenic/regulatory variant near MCM8 strongly linked to the timing of natural menopause and primary ovarian insufficiency risk.
Missense variant in MCM8 robustly linked through large-scale meta-analyses to variation in age at natural menopause and primary ovarian insufficiency risk.
Missense variant in MCM8 associated with DNA repair integrity in germ cells and susceptibility to accelerated ovarian aging.
A missense variant in MCM8 associated with DNA helicase activity, meiotic function, and altered timing of menopause.
This variant in the MCM8 gene shows suggestive association with age at natural menopause in European American women.