rs10903108 (CLIC4-RUNX3): Human Height Variant
Key takeaways
- rs10903108 is in the CLIC4-RUNX3 locus and was identified in the largest common-variant study of human height to date, covering more than 5.4 million people.
- It is one of 12,111 independent genetic signals that together account for nearly all of the common genetic contribution to adult height.
- All 12,111 height-associated variants explain about 40% of height differences in European-ancestry populations and roughly 10-20% in other ancestry groups.
- GTEx tissue data show the alternate allele is linked to reduced CLIC4 gene activity in the pancreas and increased NCMAP gene activity in tibial nerve tissue.
Key takeaways
- rs10903108 is in the CLIC4-RUNX3 locus and was identified in the largest common-variant study of human height to date, covering more than 5.4 million people.
- It is one of 12,111 independent genetic signals that together account for nearly all of the common genetic contribution to adult height.
- All 12,111 height-associated variants explain about 40% of height differences in European-ancestry populations and roughly 10-20% in other ancestry groups.
- GTEx tissue data show the alternate allele is linked to reduced CLIC4 gene activity in the pancreas and increased NCMAP gene activity in tibial nerve tissue.
What the research says A genome-wide association study (GWAS - a method that scans the genome to find statistical links between genetic variants and a trait) of up to 5,380,080 individuals across 281 studies identified 12,111 independent single-nucleotide polymorphisms (SNPs - single-letter differences in DNA sequence) significantly associated with adult height, clustered within approximately 7,209 genomic segments averaging about 90 kilobases in length. Together, these variants account for roughly 40% of phenotypic variance in height (the share of height differences that can be statistically explained) in populations of predominantly European ancestry and roughly 10-20% in other ancestries. Effect sizes and associated genomic regions were broadly consistent across ancestry groups, with lower prediction accuracy in non-European populations attributed to differences in linkage disequilibrium (the correlation structure among nearby variants) and allele frequency rather than distinct biology.
Reported associations
- Adult height: rs10903108, in this locus, was identified as one of 12,111 independent SNPs significantly associated with adult height in a multi-ancestry GWAS of up to 5,380,080 participants; together, these 12,111 SNPs explain roughly 40% of height variance in European-ancestry populations, but a per-SNP effect size for rs10903108 specifically was not reported in the supplied study text.
Evidence quality The primary association for this locus comes from a very large GWAS involving up to 5,380,080 individuals from 281 contributing studies, representing the most statistically powered common-variant height study as of its 2022 publication. The authors describe the European-ancestry map as essentially saturated, meaning additional common variants with meaningful effects on height are unlikely to be discovered in that ancestry group using current approaches. Prediction accuracy is substantially lower in non-European populations (roughly 10-20% compared with about 40% in European-ancestry groups), a limitation the authors attribute to differences in linkage disequilibrium and allele frequency rather than genuinely different underlying biology. No per-SNP effect size for rs10903108 is provided in the supplied study text, and no replication data specific to this variant were included in the provided evidence.
Tissue-specific expression effects
- CLIC4: the alternate allele at rs10903108 is associated with reduced expression of this gene in pancreatic tissue GTEx Portal.
- NCMAP: the alternate allele at rs10903108 is associated with increased expression of this gene in tibial nerve tissue GTEx Portal.
Lifestyle considerations No lifestyle considerations on file for this variant.
Frequently asked questions
What is rs10903108?
rs10903108 is a common genetic variant located in the CLIC4-RUNX3 genomic region. It was identified as one of 12,111 independent variants significantly associated with adult height in a genome-wide study of more than 5.4 million people.
Is rs10903108 linked to height?
Yes. A genome-wide study of up to 5,380,080 individuals included this variant among 12,111 independent SNPs significantly associated with adult height. An individual effect size for this specific variant was not reported in the available study text.
What genes are in the CLIC4-RUNX3 region?
The region spans the CLIC4 and RUNX3 genes. Tissue expression data from GTEx also show effects on NCMAP, a gene active in tibial nerve tissue. Which specific gene or genes drive the height association has not been established by the provided studies.
How strong is the evidence behind rs10903108?
The height association comes from the largest common-variant GWAS published to date, with more than 5.4 million participants across 281 studies. The authors describe the European-ancestry findings as essentially saturated, though prediction accuracy is substantially lower in non-European ancestry groups.
Does rs10903108 affect gene activity in specific tissues?
Yes. GTEx data show the alternate allele is linked to reduced CLIC4 gene activity in pancreatic tissue and increased NCMAP gene activity in tibial nerve tissue. These are gene expression findings and do not establish a connection to specific diseases or clinical outcomes.