rs11773147 (TRA2A): Blood Cells and Memory Genetics

Key takeaways

• This variant at the TRA2A - CLK2P1 locus has been examined in large-scale research on blood cell traits and late-life memory performance
• The ALT allele is associated with reduced expression of a nearby gene (ENSG00000234286) across seven tissues, including esophagus lining, tibial nerve, skin, thyroid, and visceral abdominal fat
• The same ALT allele is linked to increased expression of CCDC126 in EBV-transformed lymphocytes (a laboratory model for B immune cells)
• Blood cell research at this locus spanned over 746,000 individuals from five global populations; memory research included over 27,500 older adults with sex-specific analyses
• Precise trait-level effect sizes for this specific variant are not reported in the available evidence, and its trait associations should be considered preliminary

What the research says GTEx v11 eQTL data from 953 donors show the ALT allele at this locus reduces expression of ENSG00000234286 across seven tissues, with effect sizes (log2-normalized) ranging from -0.40 in visceral adipose tissue to -0.50 in esophagus mucosa, all at genome-wide significance (p-values 2.3e-10 to 7.1e-16) GTEx Portal. The same allele increases CCDC126 expression in EBV-transformed lymphocytes (effect size +0.54, p=3.0e-12) GTEx Portal. This locus was included in a trans-ethnic meta-analysis of 15 hematological traits in 746,667 individuals from five global populations, and in a sex-stratified genome-wide study of late-life memory composite scores in 27,583 older adults drawn from four cohorts of cognitive aging.

Reported associations

• Hematological (blood cell) traits: A trans-ethnic meta-analysis of 15 blood cell measures - including red cell, white cell, and platelet indices - in 746,667 individuals from European, African, East Asian, South Asian, and Hispanic/Latino populations identified this locus; the study confirmed 83 of 88 testable novel associations in an independent replication cohort (the Million Veteran Program), with 44 meeting a Bonferroni-adjusted significance threshold of P<6e-4
• Late-life memory performance: A sex-stratified genome-wide study of harmonized memory composite scores in 27,583 older adults (11,942 males, 15,641 females) drawn from four cohorts of cognitive aging and Alzheimer's disease research examined this locus; the study found memory heritability to be comparable across sexes, with some sex-specific contributing loci identified

Evidence quality The most directly quantified evidence for rs11773147 comes from GTEx v11 eQTL analyses (953 donors), which document highly significant expression effects across seven tissues for ENSG00000234286 and in lymphocytes for CCDC126, with all p-values well below conventional genome-wide significance thresholds GTEx Portal. The blood cell GWAS used a large, ancestry-diverse sample (N=746,667) and demonstrated replication; that study also showed trans-ethnic fine-mapping narrowed 95% credible variant sets by approximately 30% versus European-only analyses, improving localization precision. The memory GWAS used a more modest sample (N=27,583) with harmonized composite scores from four independent cohorts, enabling cross-study comparison. Neither study's available text reports a specific p-value or effect size for rs11773147 at the blood cell or memory trait level, so the strength of these trait associations cannot be precisely determined from the available evidence.

Tissue-specific expression effects

• ENSG00000234286: The ALT allele is associated with reduced expression in esophagus mucosa, tibial nerve, esophagus muscularis, sun-unexposed suprapubic skin, thyroid, sun-exposed lower leg skin, and visceral adipose tissue GTEx Portal
• CCDC126: The ALT allele is associated with increased expression in EBV-transformed lymphocytes GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.