Expressive

rs12211124 (GCM2-SYCP2L): Reproductive Aging

Key takeaways

  • Identified in a GWAS of up to 67,029 Japanese women as one of 26 signals for the timing of puberty or menopause
  • Allele frequencies at reproductive aging loci differ by an average of 17% between Japanese and European populations, so findings may not fully generalize across ancestries
  • The alternate allele is linked to higher SYCP2L expression in pancreas and lower expression in multiple brain regions, testis, and whole blood
  • Evidence comes from a single large study; no independent replication specific to this locus is available in the current data

Key takeaways

  • Identified in a GWAS of up to 67,029 Japanese women as one of 26 signals for the timing of puberty or menopause
  • Allele frequencies at reproductive aging loci differ by an average of 17% between Japanese and European populations, so findings may not fully generalize across ancestries
  • The alternate allele is linked to higher SYCP2L expression in pancreas and lower expression in multiple brain regions, testis, and whole blood
  • Evidence comes from a single large study; no independent replication specific to this locus is available in the current data

What the research says A GWAS of up to 67,029 Japanese women identified 26 genetic loci at genome-wide significance (P < 5 x 10-8) for reproductive aging (puberty timing and age at menopause), with the GCM2 - SYCP2L locus (rs12211124) among the identified signals PMID 30242230. Genotype-array heritability (the share of trait variation attributable to measured genetic variants) was 10.4% for menopause and 13% for menarche in this Japanese cohort, substantially lower than European estimates of 36% and 32%, respectively PMID 30242230. Allele frequencies at known reproductive aging signals differed by an average of 17% between Japanese and European populations, and 23 such signals were entirely absent (monomorphic) in the Japanese dataset PMID 30242230.

Reported associations

  • Reproductive aging (puberty timing or age at menopause): This locus was among 26 signals reaching genome-wide significance (P < 5 x 10-8) in a Japanese ancestry GWAS of up to 67,029 women; no variant-specific effect size is reported in the available study excerpt PMID 30242230.

Evidence quality The association derives from a single large Japanese GWAS (up to 67,029 women for menarche timing, 43,861 for menopause timing) at the standard genome-wide significance threshold of P < 5 x 10-8 PMID 30242230. No odds ratio or beta coefficient specific to rs12211124 is reported in the provided study excerpt. The study demonstrates broad directional consistency (same allele raising or lowering the trait) between Japanese and European populations for many reproductive aging signals, at 88.4% for menopause-related and 81.0% for menarche-related loci, but also identifies substantial population-level differences in allele frequencies and effect sizes PMID 30242230. No independent replication of this locus specifically is described in the available data, and the finding should be considered preliminary.

Tissue-specific expression effects

  • SYCP2L: The alternate allele at this locus is associated with increased expression in pancreas and cultured fibroblasts, and with reduced expression in cerebellum, anterior cingulate cortex, nucleus accumbens (basal ganglia), cerebellar hemisphere, testis, and whole blood GTEx Portal.

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What is rs12211124?

rs12211124 is a genetic variant located near the GCM2 and SYCP2L genes. It was identified in a large genome-wide study of Japanese women as one of 26 signals associated with the timing of puberty or menopause.

What traits is rs12211124 associated with?

The variant has been linked to reproductive aging traits, specifically age at menarche (first menstrual period) and age at natural menopause, in a genome-wide association study of Japanese ancestry.

Does rs12211124 affect gene expression?

GTEx data shows the alternate allele is linked to increased SYCP2L expression in pancreas and cultured fibroblasts, and reduced expression in several brain regions, testis, and whole blood. These are tissue-level expression signals and do not directly predict health outcomes.

Are the rs12211124 findings the same in European populations?

Not necessarily. The research notes widespread differences in allele frequencies and effect sizes between Japanese and European populations at reproductive aging loci, with an average 17% allele frequency gap and 23 such loci entirely absent from the Japanese dataset.

How strong is the evidence for rs12211124?

The association reached genome-wide significance (P < 5 x 10-8) in a cohort of up to 67,029 Japanese women, which is a stringent statistical threshold. However, no independent replication of this specific locus is included in the available data, so the finding should be considered preliminary.