rs10489209 (SFT2D2): Infertility GWAS Locus
Key takeaways
- Identified as one of 25 genome-wide significant infertility loci in a study of over 780,000 participants across seven cohorts.
- The alternate allele increases SFT2D2 expression in ovary and decreases it in liver.
- This variant also reduces expression of TBX19, a pituitary-development gene, across blood, spleen, and skin.
- The evidence base is a single large meta-analysis; independent replication specific to this locus was not described in available study materials.
Key takeaways
- Identified as one of 25 genome-wide significant infertility loci in a study of over 780,000 participants across seven cohorts.
- The alternate allele increases SFT2D2 expression in ovary and decreases it in liver.
- This variant also reduces expression of TBX19, a pituitary-development gene, across blood, spleen, and skin.
- The evidence base is a single large meta-analysis; independent replication specific to this locus was not described in available study materials.
What the research says A genome-wide association meta-analysis across seven cohorts studied up to 42,629 infertility cases and 740,619 controls, identifying 25 genetic loci for male and female infertility and up to 269 loci for reproductive hormones including follicle-stimulating hormone, luteinizing hormone, estradiol, and testosterone. The locus spanning SFT2D2 (a gene encoding a vesicle-trafficking protein) and RNU6-1310P (a small nuclear RNA pseudogene) was among the 25 identified infertility loci. Separately, GTEx v11 eQTL (expression quantitative trait locus, a type of genetic variant that influences how much a nearby gene is produced in a given tissue) data from 953 donors show that the alternate allele at this locus reduces SFT2D2 activity in liver and raises it in ovary, while also reducing expression of TBX19 (a transcription factor important in pituitary cell development) across blood, spleen, skin, and other peripheral tissues GTEx Portal.
Reported associations
- Female and male infertility: Identified as one of 25 genome-wide significant loci in a meta-analysis of up to 42,629 cases and 740,619 controls across seven cohorts of primarily European ancestry; specific effect sizes for this locus were not reported in the available study text.
- Reproductive hormone levels (FSH, LH, estradiol, testosterone): The same study performed sex-specific meta-analyses for these hormones in n = 6,095-246,862 participants; specific association statistics for this locus with hormone levels were not available in the provided excerpt.
- SFT2D2 tissue expression (eQTL): The alternate allele is associated with reduced SFT2D2 expression in liver (slope -0.47, p = 4.3e-21), increased expression in ovary (slope +0.29, p = 2.2e-7), and increased expression in cervical spinal cord (slope +0.22, p = 2.7e-6) GTEx Portal.
- TBX19 tissue expression (eQTL): The alternate allele is associated with reduced TBX19 expression in EBV-transformed lymphocytes (slope -0.31, p = 2.9e-14), spleen (slope -0.22, p = 1.3e-5), whole blood (slope -0.17, p = 1.3e-10), sun-exposed skin (slope -0.16, p = 2.4e-11), and cultured fibroblasts (slope -0.11, p = 1.5e-9) GTEx Portal.
Evidence quality The primary genetic association evidence comes from a single large GWAS meta-analysis spanning up to 42,629 infertility cases and 740,619 controls across seven cohorts of primarily European ancestry. The scale is substantial, but case definitions varied across cohorts (including primary care records, hospital records, and self-report), and the available study excerpt does not include specific effect size statistics or p-values for this individual locus. Notably, the study authors report that female infertility shows no local or genome-wide genetic correlation with reproductive hormones, a finding that warrants caution when inferring hormonal mechanisms from infertility-associated loci. The GTEx eQTL evidence is drawn from 953 donors and includes highly significant associations across multiple tissues for both SFT2D2 and TBX19 GTEx Portal. No conflicting studies were identified in the provided sources, and the overall infertility association evidence should be considered preliminary pending locus-specific replication.
Tissue-specific expression effects
- SFT2D2: The alternate allele is associated with reduced expression in liver, increased expression in ovary, and increased expression in cervical spinal cord GTEx Portal.
- TBX19: The alternate allele is associated with reduced expression in EBV-transformed lymphocytes, spleen, whole blood, sun-exposed skin, and cultured fibroblasts GTEx Portal.
Lifestyle considerations No lifestyle considerations on file for this variant.
Frequently asked questions
What is the SFT2D2 gene and what does it do?
SFT2D2 encodes a protein involved in the cell's vesicle-trafficking machinery, helping move molecules between compartments inside cells. GTEx data show that the rs10489209 variant alters how much of this protein is produced in ovary and liver, in opposite directions.
Is rs10489209 linked to infertility?
It was identified as one of 25 genome-wide significant loci for male and female infertility in a meta-analysis of up to 42,629 cases and 740,619 controls across seven cohorts. Specific effect sizes for this locus were not available in the materials reviewed.
What is TBX19 and why does its expression matter here?
TBX19 (also called TPIT) is a transcription factor important in developing pituitary cells that produce the hormone ACTH. GTEx data show that the alternate allele at rs10489209 is linked to lower TBX19 activity in blood, spleen, skin, and fibroblasts, though the clinical relevance of this eQTL effect has not been established.
Does this variant affect reproductive hormones?
The same infertility study analyzed follicle-stimulating hormone, luteinizing hormone, estradiol, and testosterone in up to 246,862 participants, but specific association data for rs10489209 with any of these hormone levels were not described in the available study excerpt.
How strong is the evidence linking rs10489209 to infertility?
The evidence comes from one large meta-analysis across seven cohorts with varied case definitions. The full effect size and p-value for this specific locus were not available in the provided text, making it difficult to assess strength of evidence beyond genome-wide significance.