rs12211410 (TNXB): Educational Attainment Variant
Key takeaways
- rs12211410 (TNXB locus) was identified as genome-wide significant for years of schooling in a study of over 1.1 million individuals.
- Individual variant effects are small: the median bias-corrected effect across the study's significant variants was about 1.7 weeks of additional schooling per allele.
- The variant's influence on schooling showed heterogeneity across environments, suggesting social context modifies its apparent effect.
- rs12211410 increases TNXA gene expression in seven tissues including adrenal gland, ovary, testis, pituitary gland, and tibial nerve.
- It also reduces RNF5 expression in skeletal muscle, though the functional significance of this is not yet established.
Key takeaways
- rs12211410 (TNXB locus) was identified as genome-wide significant for years of schooling completed in a study of over 1.1 million individuals.
- Individual variant effects on educational attainment are small: the median bias-corrected effect across the study's 1,271 significant variants was about 1.7 weeks of additional schooling per allele.
- The variant's influence on schooling showed heterogeneity across environments, meaning social context appears to modify its apparent effect.
- rs12211410 increases expression of TNXA (a partial duplicate of the TNXB gene) in seven tissues including adrenal gland, ovary, testis, pituitary gland, and tibial nerve.
- It also reduces RNF5 expression in skeletal muscle, though the functional significance of this is not established by the evidence provided.
What the research says rs12211410 sits within or adjacent to the TNXB (Tenascin XB) locus on chromosome 6p21 and was identified among 1,271 genome-wide significant single-nucleotide polymorphisms (SNPs, common positions in the genome where individuals differ by a single DNA letter) for educational attainment measured as years of schooling completed in a meta-analysis of approximately 1.1 million European-descent individuals. The study found that the significant variants as a group implicated genes involved in brain development and neuron-to-neuron communication, and reported heterogeneous effects across environments, meaning the variants' apparent influence on schooling was not uniform across different social and environmental settings. In tissue-expression data from GTEx v11 (953 donors), rs12211410 is separately identified as an eQTL (a variant associated with how actively a nearby gene is expressed) for both TNXA, a partial duplicate of the TNXB gene in the same chromosomal region, and for RNF5 (Ring Finger Protein 5) in skeletal muscle, though neither molecular effect has a directly established connection to educational attainment GTEx Portal.
Reported associations
- Educational attainment (years of schooling): Identified as one of 1,271 genome-wide significant variants in a sample of approximately 1.1 million European-descent individuals; the median Bayesian-adjusted effect size (a statistical correction for the tendency of SNPs selected as significant to overestimate their true effects) across all significant variants corresponded to approximately 1.7 weeks of additional schooling per allele (5th to 95th percentile: 1.1 to 2.6 weeks per allele); a polygenic score from the primary analysis explained approximately 11% of variance in educational attainment, rising to approximately 12% under a joint multi-phenotype analysis that also explained 7 to 10% of variance in cognitive performance.
- TNXA expression (seven tissues): This variant is an eQTL for TNXA with increased expression observed in adrenal gland, ovary, testis, pituitary gland, tibial nerve, visceral adipose tissue, and esophageal muscularis; effect slopes ranged from +0.60 to +1.07 across these tissues (all FDR < 0.05, GTEx v11, 953 donors) GTEx Portal.
- RNF5 expression (skeletal muscle): Associated with reduced RNF5 expression in skeletal muscle (effect slope -0.31, p = 6.3e-28, GTEx v11, 953 donors) GTEx Portal.
Evidence quality The educational attainment association derives from one of the largest behavioral GWAS ever conducted, with approximately 1.1 million European-descent participants. Of the 1,271 genome-wide significant SNPs (p < 5e-8), 995 held significance at the stricter threshold of p < 1e-8. LD Score regression indicated that roughly 5% of observed test-statistic inflation reflected bias, with the remainder attributed to genuine polygenic signal. Within-family analyses across 22,135 sibling pairs provide partial evidence against confounding by population stratification, though within-family effect magnitudes may differ from the reported population-level estimates. The sample was restricted to European-descent individuals, limiting generalizability to other ancestry groups. No PMID was available in the study metadata provided for this entry. The GTEx eQTL data are based on 953 donors at FDR < 0.05 across multiple tissue types; seven tissues showed TNXA expression effects and one showed an RNF5 effect, but no brain-tissue eQTL for this variant was reported in the GTEx data provided GTEx Portal.
Tissue-specific expression effects
- TNXA: Increased expression in adrenal gland, ovary, testis, pituitary gland, tibial nerve, visceral adipose tissue, and esophageal muscularis GTEx Portal.
- RNF5: Reduced expression in skeletal muscle GTEx Portal.
Lifestyle considerations No lifestyle considerations on file for this variant.
Frequently asked questions
What is the TNXB gene?
TNXB (Tenascin XB) is a gene on chromosome 6 that encodes a large protein found in connective tissue and the extracellular matrix. The rs12211410 variant is annotated to the TNXB locus, though GTEx eQTL data show its clearest expression effects are on TNXA, a closely related partial duplicate in the same chromosomal region.
Is rs12211410 linked to educational attainment?
Yes. It was identified as one of 1,271 genome-wide significant variants for years of schooling in a meta-analysis of approximately 1.1 million European-descent individuals. Individual SNP effects are small, and these findings describe population-level statistical associations, not individual predictions.
Does rs12211410 affect how genes are expressed in the body?
Yes. GTEx data from 953 donors show that rs12211410 is an eQTL (a variant that predicts gene activity levels) for TNXA in seven tissues and for RNF5 in skeletal muscle. These are molecular observations and do not have a directly established link to any health outcome.
Does rs12211410 affect brain gene expression?
The GTEx data provided for rs12211410 do not include brain tissues among its significant eQTL findings. Its documented expression effects are in peripheral and endocrine tissues such as adrenal gland, ovary, testis, tibial nerve, and visceral fat.
How much does rs12211410 contribute to educational attainment?
The contribution of any single variant from this study is small. The median bias-corrected effect across all 1,271 significant SNPs was about 1.7 weeks of additional schooling per allele, and the full set of significant variants together (as a polygenic score) explained roughly 11% of educational attainment variance, with the rest driven by other genetic variants, environmental factors, and their interactions.