rs10848218 (STX2): Height-Associated Variant

Key takeaways

• rs10848218 is one of 12,111 common genetic variants linked to adult height in a genome-wide study of 5.4 million individuals.
• The variant sits near STX2 (Syntaxin-2) and the pseudogene RNU6-1077P, a DNA sequence resembling a functional RNA gene but not known to produce a functional product.
• GTEx tissue data show the effect allele consistently increases STX2 expression in lung, whole blood, thyroid, fat tissue, tibial nerve, and skin.
• Height association evidence is strongest for European-ancestry populations; prediction accuracy falls to approximately 10-20% in other ancestries.

What the research says rs10848218, located near the STX2 (Syntaxin-2) - RNU6-1077P locus, was identified as one of 12,111 independent SNPs (single-nucleotide polymorphisms, meaning single-letter changes in DNA sequence) with genome-wide-significant associations with adult height in a study of up to 5,380,080 individuals across 281 research cohorts and five ancestry groups PMID 36224396. Collectively, these variants account for approximately 40% of the phenotypic variance in height (the measurable spread of heights across individuals) in European-ancestry populations and around 10-20% in other ancestries PMID 36224396. Independent expression-QTL (eQTL) data, which measure how a variant influences nearby gene activity, from GTEx v11 show the effect allele at this locus increases STX2 expression across multiple tissues GTEx Portal.

Reported associations

• Adult height: one of 12,111 genome-wide-significant height-associated common SNPs; the full set accounts for approximately 40% of phenotypic variance in height (45% when including variants from the broader HapMap 3 reference panel) in European-ancestry populations, in a sample of up to 5,380,080 individuals PMID 36224396

Evidence quality The height association at this locus is drawn from a study with up to 5,380,080 participants across 281 cohorts, comprising European (75.8%), East Asian (8.8%), Hispanic (8.5%), African (5.5%), and South Asian (1.4%) ancestry groups PMID 36224396. All 12,111 reported associations reached genome-wide significance, and the authors characterize the common-variant map as near-saturated for European-ancestry populations. Prediction accuracy is notably lower in non-European populations, falling to approximately 10-20% compared with 40% in European populations; the authors attribute this gap to linkage disequilibrium differences (the tendency of nearby genetic variants to be co-inherited as a block, which differs between populations) and allele-frequency variation rather than distinct causal biology PMID 36224396. The study text as provided does not include a per-SNP effect size for rs10848218 specifically. GTEx eQTL findings are based on 953 donors at FDR less than 0.05 GTEx Portal.

Tissue-specific expression effects

• STX2: the effect allele is linked to increased expression in lung, tibial nerve, whole blood, thyroid, subcutaneous fat, visceral fat (omentum), and sun-unexposed skin GTEx Portal
• ENSG00000256250: the effect allele is linked to reduced expression in cultured fibroblasts GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.