rs11708164 (TRANK1): Height and Brain Expression

Key takeaways

• rs11708164 was identified among 12,111 common DNA variants linked to adult human height in a genome-wide study of 5.4 million people, one of the largest genetic analyses ever conducted.
• The variant is associated with reduced activity of the TRANK1 gene in the brain cortex, esophagus lining, and whole blood.
• It also reduces expression of CBX3P10 across lab-cultured immune cells, the pituitary gland, the small intestine, and the spleen.
• A nearby gene, LRRFIP2, shows mildly increased expression in sun-exposed skin in people who carry this variant.
• These expression effects describe molecular mechanisms and do not directly predict any health outcome.

What the research says rs11708164, a common single-nucleotide polymorphism (SNP - a single-letter change in the DNA sequence) near the gene TRANK1, is one of 12,111 independent SNPs identified as significantly associated with adult human height in a meta-analysis of 5,380,080 individuals drawn from 281 studies across five ancestral groups; those variants together account for approximately 40 to 45 percent of the phenotypic variance in height among people of European ancestry, covering genomic segments spanning roughly 21 percent of the human genome. In tissue-level gene-expression analyses, the alternate allele at this locus is consistently associated with reduced expression of TRANK1 in the esophagus mucosa, brain cortex, and whole blood, and with reduced expression of CBX3P10 across four additional tissues including the pituitary gland and spleen GTEx Portal. The same allele also shows a smaller signal of increased LRRFIP2 expression in sun-exposed lower-leg skin GTEx Portal.

Reported associations

• Adult human height: rs11708164 is among 12,111 independent SNPs reaching genome-wide significance in a meta-analysis of 5,380,080 individuals across five ancestral groups; no variant-specific effect size was provided in the source text.
• TRANK1 expression (esophagus mucosa, brain cortex, whole blood): the alternate allele is associated with reduced TRANK1 gene expression across all three tissues GTEx Portal.
• CBX3P10 expression (EBV-transformed lymphocytes, pituitary, small intestine, spleen): the alternate allele is linked to reduced CBX3P10 expression across four tissue types GTEx Portal.
• LRRFIP2 expression (sun-exposed lower-leg skin): the alternate allele is associated with modestly increased LRRFIP2 expression in this tissue GTEx Portal.

Evidence quality The height association derives from a well-powered meta-analysis of approximately 5.38 million individuals, roughly 76 percent of whom were of European ancestry, pooled across 281 contributing studies; the 12,111 identified SNPs collectively account for nearly all common-variant heritability for height in European-ancestry populations, though prediction accuracy drops to roughly 10 to 20 percent in non-European groups. No individual p-value or effect size was reported in the source text for rs11708164 specifically. The tissue-expression associations from GTEx v11 (953 donors) all meet FDR less than 0.05; the strongest signals are CBX3P10 in EBV-transformed lymphocytes (p = 1.2 x 10^-16), CBX3P10 in the pituitary gland (p = 3.4 x 10^-14), and TRANK1 in esophagus mucosa (p = 3.6 x 10^-12); the LRRFIP2 signal in sun-exposed skin (p = 3.2 x 10^-5) is the least statistically robust of the three affected genes GTEx Portal. No conflicting findings are noted across the provided sources.

Tissue-specific expression effects

• CBX3P10: reduced expression in EBV-transformed lymphocytes (lab-cultured immune cells), the pituitary gland, the small intestine terminal ileum, and the spleen GTEx Portal.
• TRANK1: reduced expression in the esophagus mucosal lining, the brain cortex, and whole blood GTEx Portal.
• LRRFIP2: increased expression in sun-exposed skin on the lower leg GTEx Portal.

Lifestyle considerations No lifestyle considerations on file for this variant.