rs10467770 (CHD8): Height Variant and TOX4 Expression
Key takeaways
- rs10467770 is one of 12,111 genetic variants linked to adult height in a study of 5.4 million people
- It increases TOX4 gene expression in at least seven tissues, including frontal cortex, tibial artery, and skeletal muscle
- A separate effect reduces expression of ENSG00000305385 in testis
- Height variants like this one together explain roughly 40% of height differences in European populations
- No lifestyle or drug-response data are currently on file for this variant
Key takeaways
- rs10467770 is one of 12,111 genetic variants linked to adult height in a study of 5.4 million people
- It increases TOX4 gene expression in at least seven tissues, including frontal cortex, tibial artery, and skeletal muscle
- A separate effect reduces expression of ENSG00000305385 in testis
- Height variants like this one together explain roughly 40% of height differences in European populations
- No lifestyle or drug-response data are currently on file for this variant
What the research says A meta-analysis of 5.4 million individuals from 281 studies identified 12,111 independent variants significantly associated with adult height, clustering within 7,209 non-overlapping genomic segments averaging roughly 90 kilobases each; rs10467770, near the CHD8 locus, is among these associations. The full set of height-associated variants explains approximately 40% of phenotypic variance in European-ancestry populations but only around 10-20% in populations of other ancestries, reflecting differences in linkage disequilibrium and allele frequency. GTEx v11 data from 953 donors (FDR < 0.05) show that the alternate allele at this locus is associated with increased TOX4 expression across seven tissues and with reduced expression of ENSG00000305385 in testis GTEx Portal.
Reported associations
- Adult height: One of 12,111 independent SNPs reaching genome-wide significance in a multi-ancestry GWAS of 5.4 million participants across 281 studies; the associated regions cover approximately 21% of the genome and collectively account for nearly all common-SNP-based heritability for height
- TOX4 expression (multiple tissues): Increased expression in frontal cortex (BA9), tibial artery, thyroid, lung, subcutaneous adipose tissue, skeletal muscle, and sun-exposed lower-leg skin GTEx Portal
- ENSG00000305385 expression (testis): Reduced expression in testis GTEx Portal
Evidence quality The height association is supported by one of the largest genetic meta-analyses conducted to date (n=5.4 million, 281 studies), with associations passing genome-wide significance thresholds; the authors report that associated regions are enriched for biologically relevant genes, and the density of independent associations varies meaningfully across the genome. Prediction accuracy reaches approximately 40% of phenotypic height variance in European-ancestry populations but falls to roughly 10-20% in other ancestry groups, a gap the study attributes to differences in linkage disequilibrium (the tendency for nearby variants to be inherited together) and allele frequency across populations. The eQTL signals from GTEx (953 donors, FDR < 0.05) show consistent increased expression of TOX4 across seven independent tissues, providing convergent support for a functional effect at this locus GTEx Portal. The individual effect size of this locus on height is not enumerated in the provided study text, and the functional connection between the observed expression changes and height biology is not established in the available data.
Tissue-specific expression effects
- TOX4: Increased expression in frontal cortex (BA9), tibial artery, thyroid, lung, subcutaneous adipose tissue, skeletal muscle, and sun-exposed lower-leg skin; the tibial artery association is the strongest signal (p=4.3e-11) GTEx Portal
- ENSG00000305385: Reduced expression in testis (p=1.9e-6) GTEx Portal
Lifestyle considerations No lifestyle considerations on file for this variant.
Frequently asked questions
What is rs10467770?
rs10467770 is a common genetic variant located near the CHD8 gene. It is one of 12,111 independent variants significantly associated with adult height in a genome-wide study of 5.4 million individuals across diverse ancestries.
Is rs10467770 linked to height?
Yes. It is among 12,111 independent genetic signals identified in a large multi-ancestry genome-wide association study of 5.4 million people. The full set of these variants explains roughly 40% of height variation in people of European ancestry, and around 10-20% in other ancestry groups.
What genes does rs10467770 affect?
GTEx v11 data show that this variant is associated with increased expression of TOX4 in at least seven tissues, including the brain's frontal cortex, tibial artery, and skeletal muscle. It is also linked to reduced expression of ENSG00000305385 in testis. These are gene-expression effects, and their functional connection to height has not been established in the available data.
What does the CHD8 gene do?
The provided studies do not describe CHD8 function directly. rs10467770 is catalogued near CHD8, but the available data covers its association with height and its tissue-specific effects on TOX4 and ENSG00000305385 expression.
How reliable is the height association for rs10467770?
The association comes from one of the largest genetic studies ever conducted, with 5.4 million participants across 281 studies, and the variant passes genome-wide significance thresholds. The specific effect size for this variant alone is not reported in the available study text.