DENND1A rs10986105: What Your Genotype Means
The single nucleotide polymorphism rs10986105 is an intronic DNA variant located within the DENND1A gene on chromosome 9. Genome-wide association studies have identified it as a susceptibility marker associated with polycystic ovary syndrome (PCOS), ovarian hyperandrogenism, and alterations in androgen-producing theca cell activity. However, clinical evidence remains limited because it confers only modest changes in relative risk and exhibits population-specific variability.
What each genotype means
Typical risk profile
You carry two copies of the common A allele for rs10986105 in the DENND1A gene. In genome-wide association studies across diverse ancestries, this genotype has not been linked to the heightened androgen levels or increased susceptibility to polycystic ovary syndrome (PCOS) observed with the alternative allele. However, PCOS is a multifactorial condition influenced by many other genetic variants and environmental factors.
Carried by roughly 40% to 45% of individuals of European and East Asian ancestries.
Slightly increased PCOS risk
You carry one copy of the C risk allele for this variant within the DENND1A gene. Published association studies in European, East Asian, and other cohorts indicate that carrying a single risk allele confers a modest statistical increase in the risk for polycystic ovary syndrome (PCOS) and elevated androgen levels. Because overall risk is shaped by multiple genetic loci and lifestyle factors, having one risk allele is neither diagnostic nor a guarantee that PCOS will develop.
Carried by approximately 45% of individuals in European and East Asian populations.
Moderately elevated PCOS risk
You carry two copies of the C risk allele for rs10986105 in the DENND1A gene. In epidemiological and genetic association studies, this homozygous genotype has been correlated with higher odds of polycystic ovary syndrome (PCOS), ovarian theca cell hyperfunction, and hyperandrogenism compared to the baseline genotype. This reflects a statistical susceptibility rather than a direct clinical diagnosis, as many complex factors contribute to endocrine and reproductive health.
Carried by approximately 10% to 15% of individuals of European and East Asian ancestries.
Genomic Location and Characteristics
Variant rs10986105 is mapped to the long arm of chromosome 9 at cytogenetic band 9q33.3 within an intronic region of the DENND1A (DENN domain containing 1A) gene. Because rs10986105 resides within non-coding sequence rather than directly altering an amino acid code, it does not rewrite the primary structural sequence of the encoded protein. Instead, intronic variants like rs10986105 frequently serve as tagging markers that reside in strong linkage disequilibrium with other regulatory variants, or they may directly influence regulatory processes such as alternative pre-mRNA splicing, nuclear factor binding, or transcription efficiency. In genome builds based on the forward genomic strand, the variant typically involves a thymine (T) to cytosine (C) nucleotide transition, with the minor C allele acting as the primary risk allele identified in major reproductive GWAS reports.
Function of the DENND1A Gene
The DENND1A gene encodes a protein known as connecdenn 1, which functions as a guanine nucleotide exchange factor (GEF). Connecdenn 1 interacts directly with clathrin and adaptor protein complexes, facilitating endocytosis and regulating the activation of the small GTPase RAB35. Through these endocytic and intracellular trafficking networks, DENND1A helps govern how cell-surface receptors are internalized, recycled, or degraded. In ovarian biology, DENND1A is expressed in androgen-producing theca cells. Functional investigations have highlighted an alternative splice variant known as DENND1A.V2. When DENND1A.V2 is upregulated, it drives increased transcription of key steroidogenic enzymes—notably CYP17A1 and CYP11A1—prompting excessive androgen biosynthesis and reproducing the hyperandrogenic cellular phenotype characteristic of PCOS theca cells.
Research Findings and Strength of Evidence
The link between rs10986105 and PCOS was initially reported in large Han Chinese GWAS discovery cohorts and later replicated in women of European descent, where the C allele was tied to a higher odds of meeting National Institutes of Health diagnostic criteria for PCOS (odds ratios typically ranging between 1.4 and 1.7). Researchers also noted that the C allele correlated with elevated androgen markers in unaffected populations, suggesting a fundamental effect on androgen synthesis pathways. Despite these findings, the strength of clinical evidence is rated as limited. Several replication attempts in Middle Eastern and other ethnically diverse groups failed to demonstrate a statistically significant independent association with PCOS diagnosis or related metabolic parameters. Furthermore, rs10986105 confers small individual effect sizes rather than deterministic diagnostic outcomes, highlighting that polygenic architecture and non-genetic contributors drive PCOS development.
Population Frequency
The minor allele frequency (MAF) of rs10986105 is estimated at roughly 0.30 to 0.35 among individuals of European and East Asian ancestries. In these groups, the homozygous minor genotype (CC) appears in roughly 10% to 15% of individuals, the heterozygous genotype (CT) in approximately 40% to 45%, and the homozygous major genotype (TT) in about 40% to 50%. In contrast, allele distributions vary substantially across African, South Asian, and Middle Eastern ancestral backgrounds. Because genetic backgrounds and linkage disequilibrium blocks differ widely across distinct continental lineages, an association documented in one ancestry cannot be automatically assumed to confer identical biological risks in another.
What You Can and Cannot Do With This Information
Genotypic information for rs10986105 provides insight into personal genetic background and susceptibility trends, but it is not a clinical test. Having one or two copies of the C allele does not mean an individual has or will inevitably develop PCOS. Conversely, carrying the TT genotype does not guarantee protection against hyperandrogenism, irregular menses, or metabolic complications. PCOS is a complex, multifactorial disorder shaped by dozens of common genetic loci interacting with diet, physical activity, body composition, and endocrine physiology. Anyone experiencing irregular menstrual cycles, hirsutism, persistent acne, or difficulty conceiving should consult a licensed healthcare professional for standard diagnostic evaluations (such as pelvic ultrasonography and serum hormone testing) rather than relying on direct-to-consumer genetic variants.
How common is this variant?
The minor C allele frequency is approximately 0.30 to 0.35 in European and East Asian ancestries, but allele and genotype frequencies vary substantially across other global populations.
Frequently asked questions
Does having the rs10986105 C allele mean I have PCOS?
No. Genetic variants identified through association studies, including rs10986105, represent subtle statistical tendencies across large populations rather than direct causes of disease. A clinical diagnosis of PCOS requires formal evaluation using recognized diagnostic criteria, such as ovulatory dysfunction, androgen excess, or polycystic ovaries on ultrasound.
Why do different ethnic groups show different results for this variant?
Human populations differ in their underlying genetic architecture, including patterns of linkage disequilibrium and the frequencies of surrounding variants. An intronic variant like rs10986105 may be tightly linked to a causal regulatory element in European and East Asian groups, but uncoupled from that element in Middle Eastern or African populations.
Can this genetic result determine how I should be treated or dosed for PCOS?
No. Variant rs10986105 has no approved pharmacogenomic indications and should not be used to select or adjust medications. Any medical management, including lifestyle modifications, hormonal contraceptives, or insulin-sensitizing agents, must be determined directly with your physician or pharmacist.
How does DENND1A affect hormone production?
DENND1A plays an essential role in intracellular receptor trafficking within ovarian theca cells. Specific splice variants of this gene can increase the expression of steroid-producing enzymes like CYP17A1, leading to elevated production of androgenic hormones such as testosterone.
If I carry the TT genotype, am I protected from ovarian cysts and irregular cycles?
Carrying the TT genotype means you do not have the specific risk-associated alleles at this locus, but it does not protect you from PCOS. PCOS is polygenic and multifactorial, meaning hundreds of other genetic factors alongside environmental influences contribute to overall risk.
Sources & further reading
Educational information only, last refreshed 9/13/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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This variant in the DENND1A gene has been investigated for polycystic ovary syndrome (PCOS) susceptibility, though recent studies indicate it lacks a significant correlation with PCOS in certain populations like the Chinese Han.
Intronic variant in DENND1A associated with PCOS susceptibility; evidence suggests population-specific effects with inconsistent replication across European and Asian cohorts.
This variant in the DENND1A gene is associated with the development of polycystic ovary syndrome (PCOS) and abnormal hormone levels.