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DENND1A and Fertility: What Your rs10818854 Genotype Means

Infertility is typically defined as not conceiving after one year of trying. Many factors contribute to fertility, including age, lifestyle, underlying health conditions, and genetics. One gene that can influence reproductive hormones is DENND1A. Variants at the rs10818854 position in DENND1A are linked to changes in androgen production in ovarian cells. Higher androgen levels can interfere with regular ovulation and menstrual cycles and are commonly seen in polycystic ovary syndrome or PCOS, a leading cause of infertility in people with ovaries.

How DENND1A affects hormones and fertility

DENND1A plays a role in signaling pathways that influence androgen synthesis in ovarian theca cells. Certain variants increase activity in this pathway, which can raise ovarian androgen production. Elevated androgens may disrupt the normal development and release of eggs, contributing to irregular cycles, anovulation, and clinical features often associated with PCOS such as acne, excess hair growth, and ovarian cysts. Your genotype at rs10818854 gives insight into one genetic factor that may affect androgen-related reproductive risk, but it is not a definitive diagnosis. Many other genes, environmental exposures, and health conditions also shape fertility.

Practical steps to support reproductive and hormonal health

The following recommendations are educational and intended to support overall reproductive wellness. They are not medical advice. Discuss any changes with your healthcare provider before starting new supplements, tests, or treatments.

  • Nutrition: Focus on a whole-food, nutrient-dense diet that emphasizes vegetables, fruits, lean proteins, healthy fats, and fiber. Prioritize low-glycemic carbohydrates to help stabilize blood sugar and insulin, which can influence androgen levels. Examples include non-starchy vegetables, legumes, whole grains in moderate amounts, and berries.
  • Weight and activity: Even modest weight loss in people with overweight can improve menstrual regularity and ovulation. Aim for regular aerobic and resistance exercise to support insulin sensitivity and metabolic health.
  • Stress, sleep, and recovery: Chronic stress and poor sleep can disrupt hormones. Practices such as mindfulness, moderate physical activity, and building a consistent sleep schedule help support balanced reproductive hormones.
  • Limit endocrine disruptors: Reduce exposure to substances that mimic hormones where possible. This can include choosing BPA-free food containers, avoiding unnecessary fragrances, and minimizing exposure to pesticides by washing produce or choosing organic when feasible.
  • Consider supplements thoughtfully: Some supplements have evidence for supporting reproductive outcomes in the context of PCOS and insulin resistance. Myo-inositol is commonly used to improve ovulatory function and metabolic parameters for some people, but it should be used under healthcare supervision. Other nutrients to review with your provider include vitamin D, omega-3 fatty acids, and magnesium if deficiencies are suspected.
  • Monitor health markers: If you are concerned about PCOS or infertility, discuss targeted blood tests with your care team. Typical panels to consider include reproductive hormones (FSH, LH, estradiol, progesterone), total and free testosterone, SHBG, fasting glucose and insulin or HbA1c, lipid profile, and vitamin D. Imaging such as pelvic ultrasound may be used to evaluate ovarian morphology.

Genetic Interpretations

2 effect alleles (AA) — Higher risk for DENND1A-related PCOS

If your genotype is AA at rs10818854, you carry two copies of the effect allele. This genotype is associated with increased androgen synthesis in ovarian cells and up to approximately a twofold higher risk of developing PCOS compared to people without the effect allele.

What this may mean for you

  • Greater likelihood of higher ovarian androgen levels and symptoms such as irregular periods, infrequent ovulation, acne, or excess hair growth.
  • Increased chance of insulin resistance and metabolic features that sometimes co-occur with PCOS.
  • Higher genetic predisposition does not guarantee PCOS or infertility. Many people with this genotype have normal cycles and fertility.

Recommended considerations

  • Discuss targeted evaluation with your healthcare provider if you have symptoms: reproductive hormone testing, metabolic screening, and pelvic ultrasound as appropriate.
  • Work with a clinician or registered dietitian on a balanced, lower-glycemic eating plan and exercise program to support insulin sensitivity and ovulatory function.
  • Talk to your provider about evidence-based supplements such as myo-inositol and whether they are appropriate for you.
  • Address lifestyle factors: sleep, stress reduction, avoiding endocrine disruptors, and maintaining a healthy weight where applicable.
1 effect allele (AG) — Moderate increased risk

If your genotype is AG, you carry one copy of the effect allele. This variant is associated with increased ovarian androgen synthesis and up to an approximately twofold increased risk of PCOS compared to people without the A allele, but the effect is often smaller than with two copies.

What this may mean for you

  • A modestly higher predisposition to hormonal imbalances that can affect ovulation and menstrual regularity.
  • Potential increased sensitivity to metabolic and lifestyle factors that influence hormonal balance.
  • Carrying one effect allele is not a diagnosis. Many people with AG have typical cycles and normal fertility.

Recommended considerations

  • Be proactive about healthy eating, regular physical activity, and stress and sleep hygiene to support hormone balance.
  • If you notice menstrual irregularities, acne, or hair changes, seek medical evaluation to assess hormones and metabolic health.
  • Discuss with your clinician whether supplements such as myo-inositol or a supervised plan to support insulin sensitivity are appropriate.
  • Consider periodic monitoring of fasting glucose or HbA1c and lipids if there are metabolic risk factors in your personal or family history.
0 effect alleles (GG) — Typical risk for this variant

If your genotype is GG, you carry two copies of the non-effect allele. This is the most common genotype and is associated with typical DENND1A-related androgen production.

What this may mean for you

  • Your risk for DENND1A-related elevated ovarian androgen synthesis and PCOS is not increased based on this variant.
  • This single result does not rule out other genetic or environmental causes of infertility or hormonal imbalance.

Recommended considerations

  • Continue general reproductive wellness practices: a balanced diet, regular activity, good sleep, and stress management.
  • If you experience fertility concerns or menstrual irregularities, pursue evaluation since many factors beyond this variant can affect reproductive health.
  • Discuss routine screening and preventive care with your healthcare provider based on your broader health history.

When to talk with a healthcare provider

  • If you have irregular or absent menstrual cycles, difficulty conceiving, or symptoms of high androgens such as worsening acne or excess facial or body hair.
  • If you have metabolic concerns such as significant weight gain, fasting blood sugar abnormalities, or a family history of diabetes or cardiovascular disease.
  • Before starting supplements like myo-inositol or making major dietary or medication changes.

PlexusDx provides educational information about genetic predispositions only and does not provide medical advice, diagnosis, or treatment. Always consult your healthcare provider or a specialist for personalized medical care and before starting any new supplement, test, or treatment plan.