AuraGen — Women's Complete<br><em>Hormonal Health</em>

Condition 1 of 4

Endometriosis Polygenic Risk

Endometriosis PRS

WNT4 · GREB1 · CDKN2B-AS1 · 7p15.2 locus

Slightly elevated · 66th %ile

66th percentile

0th50th100th

GWAS-validated endometriosis variants

rs7521902 A/G

WNT4 (1p36.12)

A: Risk allele, p=1.8×10⁻¹⁵, OR~1.2

rs13394619 G/A

GREB1 (2p25.1)

A: Risk allele, p=4.5×10⁻⁸, hormonal pathway

rs12700667 G/A

7p15.2 intergenic

A: Risk allele, p=1.6×10⁻⁹

rs1537377 C/T

CDKN2B-AS1 (9p21.3)

T: Risk allele, p=1.5×10⁻⁸

rs10859871 G/A

VEZT (12q22)

G: Risk allele, p=4.7×10⁻¹⁵

rs7739264 A/G

ID4 (6p22.3)

A: Risk allele, p=6.2×10⁻¹⁰

Your endometriosis PRS is driven by the WNT4 (rs7521902) and GREB1 (rs13394619) loci — two of the most robustly replicated endometriosis GWAS signals across European and Japanese populations (Nyholt et al., Nature Genetics 2012; Mortlock et al., Human Reproduction Update 2014). WNT4 plays a critical role in female reproductive development and ovarian steroidogenesis. GREB1 is an estrogen-responsive gene implicated in endometrial proliferation. Endometriosis is diagnosed an average of 7–10 years after symptom onset. Genetic risk data can accelerate this trajectory.

Supporting literature

Nyholt et al. (2012). Genome-wide association meta-analysis identifies new endometriosis risk loci. Nature Genetics. 44, 1355–1359. 4,604 cases, 9,393 controls — established WNT4 and GREB1 loci.
Mortlock et al. (2014). Genetic variants underlying risk of endometriosis: insights from meta-analysis of eight GWAS and replication datasets. Human Reproduction Update. 20(5):702-716. Six GWS loci confirmed across populations.
Frontera et al. (2024). Dissecting the shared genetic architecture between endometriosis and PCOS. Frontiers in Endocrinology. doi:10.3389/fendo.2024.1359236

Condition 2 of 4

PCOS Polygenic Risk

Polycystic Ovary Syndrome (PCOS) PRS

LHCGR · THADA · DENND1A · INSR pathway

Average risk · 49th %ile

49th percentile

0th50th100th

GWAS-validated PCOS variants

rs2470152 C/T

LHCGR (2p16.3)

C: Wild-type, LH receptor function normal

rs13405728 A/G

THADA (2p21)

A: Wild-type, no PCOS signal

rs10818854 A/G

DENND1A (9q33.3)

A: Wild-type, clathrin pathway normal

Your PCOS PRS is at population average (49th %ile), with wild-type alleles at the three most robustly replicated PCOS GWAS loci. However, note the metabolic overlap: your TCF7L2 rs7903146 C/T genotype (T2D panel) creates insulin resistance pathways that phenotypically overlap with PCOS — particularly the metabolic subtype. Annual metabolic screening (fasting insulin, HOMA-IR, testosterone) remains appropriate.

Supporting literature

Day et al. (2015). Causal mechanisms and balancing selection inferred from genetic associations with polycystic ovary syndrome. Nature Genetics. 47, 1452–1456. First large-scale PCOS GWAS in European women.
Chen et al. (2011). Meta-analysis of eight genome-wide association studies identifies common variants associated with PCOS. Human Molecular Genetics. LHCGR, THADA, DENND1A confirmed.

Condition 3 of 4

Osteoporosis & Bone Density

Bone Mineral Density PRS

LRP5 · ESR1 · COL1A1 · RANKL/OPG pathway

Slightly elevated · 63rd %ile

63th percentile

0th50th100th

Bone density and osteoporosis variants

rs4870061 C/T

LRP5 (11q13.2)

T: Reduced Wnt/LRP5 signaling → lower peak BMD

rs1999805 G/A

ESR1 (6q25.1)

A: Altered estrogen receptor → bone resorption risk

rs9594738 C/T

RANKL (13q14.11)

T: ↑ osteoclast activity → ↓ bone density

rs2073618 G/C

OPG (8q24.12)

G: Normal OPG — partially protective

Your bone density PRS is driven by LRP5 and ESR1 variants affecting the Wnt signaling and estrogen receptor pathways respectively — two of the most important determinants of peak bone mass. Combined with your CYP2R1 vitamin D synthesis variant (Skin Genomics report), your overall bone health picture warrants proactive intervention. Estrogen's protective effect on bone makes your predicted later menopause timing (see below) a partially compensating factor.

Supporting literature

Estrada et al. (2012). Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture. Nature Genetics. 44, 491–501. N=32,961. LRP5 and ESR1 among top validated loci.
Rivadeneira & Mäkitie (2016). Osteoporosis and bone mass disorders: from gene pathways to treatments. Trends in Endocrinology & Metabolism. 27(5):262-281.

Condition 4 of 4

Predicted Age at Natural Menopause

Menopause Timing PRS — Predicted Later Onset

MCM8 · BRSK1 · UIMC1 · DACH2 pathway

Favorable — Later onset predicted

32th percentile

0th50th100th

Menopause timing variants

rs16991615 A/G

MCM8 (10q22.2)

G: Associated with later menopause onset

rs2277339 C/T

BRSK1 (9q34.3)

C: Preserved ovarian reserve signal

rs1046089 G/A

UIMC1 (5p13.3)

G: Later menopause, extended estrogen exposure

Your menopause timing PRS predicts later natural menopause onset (estimated 52–54 years), which has several compounding implications. Extended endogenous estrogen exposure is: (1) partially protective for your bone density (compensates for LRP5/ESR1 variants), (2) modestly relevant to breast cancer risk trajectory — discuss with your oncologist given your breast cancer PRS (82nd %ile), and (3) beneficial for cardiovascular protection in the perimenopausal decade. These are risk-benefit tradeoffs to discuss with your gynecologist.

Supporting literature

Stolk et al. (2012). Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways. Nature Genetics. 44, 260–268. MCM8 and BRSK1 among top loci.
Day et al. (2015). Large-scale genomic analyses link reproductive aging to hypothalamic signaling, breast cancer susceptibility and BRCA1-mediated DNA repair. Nature Genetics. 47, 1294–1303.

AuraGen Women's Health Integration

How your four findings interact

Endometriosis and PCOS share overlapping genetic architecture through Wnt signaling and metabolic pathways. Your LRP5/ESR1 bone variants and predicted later menopause create a complex estrogen-exposure picture. Your TCF7L2 metabolic burden connects PCOS risk to glucose metabolism. These four panels are not independent — they form a hormonal health narrative that a single-condition test cannot reveal.

Endometriosis WNT4 signal + PCOS — average, metabolic overlap + Bone — LRP5/ESR1 + Later menopause — estrogen extended → Gynecologist + endocrinologist team approach

Discuss endometriosis risk with your gynecologist

If you experience dysmenorrhea, pelvic pain, or subfertility, share your WNT4 and GREB1 findings. These variants, combined with symptoms, support early laparoscopic evaluation rather than years of watchful waiting.

Proactive bone health protocol — start now

1200mg calcium/day (food + supplement), 2000 IU D3 daily (especially given your CYP2R1 vitamin D synthesis variant), resistance training 3×/week. DEXA scan at perimenopause onset.

Breast cancer risk context for estrogen exposure

Your later menopause prediction extends estrogen exposure, which is one of several factors relevant to your breast cancer PRS (82nd %ile, main report). Discuss hormone therapy decisions and screening timing with your oncologist — this is particularly important at perimenopause.

⚠ Research Use Only (RUO) — Important Disclaimer

This report is provided for Research Use Only and is not FDA-cleared, FDA-approved, or CE-IVD certified. Polygenic risk scores and pharmacogenomic findings reported here are derived from peer-reviewed published genome-wide association studies (GWAS) and are provided for informational and research purposes only. These results are not diagnostic and do not predict with certainty whether any condition will or will not develop. Results must not be used as the sole basis for any medical, pharmacological, or lifestyle decision. Always consult a licensed physician, genetic counselor, or pharmacist before acting on any finding in this report. AuraGen Wellness does not practice medicine. Sequencing performed by Intelliseq sp. z o.o. © 2026 AuraGen Wellness · auragenwellness.com

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Hormonal Health