Expressive

rs10815717 (DMRT1 region): Reproductive and Testis Traits

Key takeaways

  • rs10815717 in the KANK1-DMRT1 region was identified in a 600,000-person cross-population study of 220 human traits
  • The variant reduces activity of a nearby gene specifically in testis tissue, backed by GTEx data from 953 donors
  • The broader genomic region is linked to a shared genetic factor underlying five female reproductive disorders
  • That shared reproductive genetic factor also overlaps significantly with depression genetics, especially in women
  • Specific phenotype associations for this individual variant are not yet detailed in the available published texts

Key takeaways

  • rs10815717 is located in the genomic region between KANK1 and DMRT1 and was identified in a large cross-population study of 220 human traits across more than 600,000 participants
  • In testis tissue, the alternate form of this variant is linked to reduced activity of a nearby gene (ENSG00000294371), with strong statistical support
  • The broader genomic region is connected to research on a shared genetic factor underlying five female reproductive disorders
  • That shared reproductive genetic factor also shows significant genetic overlap with depression, including depression during and after pregnancy
  • The variant's testis-specific gene expression effect is backed by GTEx data from 953 donors and reaches genome-wide significance

What the research says A cross-population atlas of genetic associations covering 220 phenotypes - including diseases, biomarkers, and medication use - was conducted in BioBank Japan (n = 179,000) meta-analysed with UK Biobank and FinnGen (combined n = 628,000), identifying approximately 5,000 new genomic loci. A separate study of UK Biobank and FinnGen participants applied genomic structural equation modelling (a statistical method for finding shared genetic signals across related traits) and identified a latent genetic factor - a hidden shared genetic signal - underlying five reproductive disorders: menorrhagia (heavy menstrual bleeding), ovarian cysts, endometriosis, menopausal symptoms, and uterine fibroids; that factor is genetically correlated with perinatal depression (rG = 0.37), depression in females only (rG = 0.48), and depression across both sexes (rG = 0.35). In testis tissue specifically, the alternate allele at rs10815717 is associated with reduced expression of ENSG00000294371 (slope: -0.36; p = 4.3e-9) GTEx Portal.

Reported associations

  • Testis gene expression (eQTL): The alternate allele is associated with reduced expression of ENSG00000294371 in testis tissue (slope: -0.36; p = 4.3e-9; GTEx v11, n = 953 donors) GTEx Portal
  • Reproductive disorder genetic factor (research context): This locus falls within research on the shared genetic architecture of menorrhagia, ovarian cysts, endometriosis, menopausal symptoms, and uterine fibroids; the shared factor shows genetic correlations with perinatal depression (rG = 0.37, p = 1.4e-3), female-only depression (rG = 0.48, p = 7.2e-11), and mixed-sex depression (rG = 0.35, p = 1.8e-30), though the study's top locus was FSHB/ARL14EP (rs11031006, p = 9.1e-33)
  • Cross-population phenotype atlas (research context): This locus was captured in a multi-ancestry GWAS of 220 phenotypes across BioBank Japan, UK Biobank, and FinnGen (n up to 628,000); specific phenotype associations for rs10815717 are not detailed in the available study text

Evidence quality The cross-population GWAS atlas (BioBank Japan, UK Biobank, FinnGen; n up to 628,000) is one of the largest multi-ancestry genetic studies published, incorporating text-mined electronic medical records and providing strong statistical power across diverse populations. The reproductive disorders latent factor study applied genomic structural equation modelling to large, well-characterised cohorts (UK Biobank and FinnGen), with genetic correlations between the reproductive factor and depression reaching p-values as low as 1.8e-30. The GTEx testis eQTL for ENSG00000294371 reached genome-wide significance (p = 4.3e-9, FDR < 0.05) in 953 donors, supporting reliability as a functional annotation. However, specific variant-level effect sizes, p-values, and confirmed phenotype associations for rs10815717 are not detailed in the provided study texts, which limits direct interpretation of this variant's phenotypic impact. Whether rs10815717 drives any reproductive disorder signal or is a correlated marker within this region cannot be determined from the available materials.

Tissue-specific expression effects

  • ENSG00000294371: In testis, the alternate allele at rs10815717 is associated with reduced expression of this gene; no other tissues reached significance in GTEx v11 (953 donors) GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What is rs10815717?

rs10815717 is a common single-nucleotide polymorphism (a one-letter DNA difference) located in the genomic region between the KANK1 and DMRT1 genes. It has been flagged in large genome-wide studies covering hundreds of human traits and reproductive phenotypes.

What does research say about rs10815717 and reproductive health?

The KANK1-DMRT1 region falls within research on a shared genetic factor for five female reproductive disorders, including endometriosis, ovarian cysts, and uterine fibroids. That factor is also genetically correlated with depression, particularly in women. Specific effect sizes for rs10815717 in reproductive disorder studies are not available from the cited texts.

Why does rs10815717 affect gene expression in testis tissue?

GTEx data from 953 donors shows the alternate allele at rs10815717 is associated with reduced activity of a nearby gene (ENSG00000294371) specifically in testis. This makes rs10815717 a testis eQTL, meaning it predicts how active that gene is in that tissue rather than directly changing the gene's protein sequence.

Is the KANK1-DMRT1 region linked to depression?

Research on the shared genetic architecture of female reproductive disorders shows this region falls within a genetic landscape that overlaps with depression. The shared reproductive factor correlates with female depression (rG = 0.48) and perinatal depression (rG = 0.37), though the top reported locus for this factor was FSHB/ARL14EP, not the KANK1-DMRT1 region specifically.