rs10814297 (SPAAR): Height-Associated Variant
Key takeaways
- rs10814297 near SPAAR was identified in a height GWAS of 5.4 million people, one of the largest genetic studies ever conducted.
- The variant reduces SPAAR expression most strongly in tibial nerve and also in skeletal muscle, stomach, and esophagus tissue.
- Height-associated SNPs like this one collectively explain about 40% of phenotypic height variance in European-ancestry populations.
- The VA Million Veteran Program's diverse-population atlas includes this locus among thousands of genome-wide associations.
- No variant-specific effect size for rs10814297 on height is reported in the available study text.
Key takeaways
- rs10814297 near SPAAR was identified in a height genome-wide association study of 5.4 million people, one of the largest genetic studies ever conducted.
- The variant reduces SPAAR expression most strongly in tibial nerve and also in skeletal muscle, stomach, and esophagus tissue.
- Height-associated SNPs like this one collectively explain about 40% of phenotypic height variance in European-ancestry populations.
- The VA Million Veteran Program's diverse-population atlas includes this locus among thousands of genome-wide associations.
- No variant-specific effect size for rs10814297 on height is reported in the available study text.
What the research says
rs10814297, near SPAAR (Striated Muscle Activator of Rho Signaling), is among 12,111 independent SNPs identified as significantly associated with adult height in a meta-analysis of approximately 5.4 million individuals from 281 contributing studies, with this set of variants collectively accounting for nearly all common SNP-based heritability of height PMID 36224396. The VA Million Veteran Program (MVP), a biobank of 635,969 participants with 29% from non-European ancestry groups, conducted genome-wide association studies across 2,068 traits and produced an atlas of 26,049 variant-trait associations, providing diverse-ancestry context for loci in this region PMID 38696054. GTEx v11 eQTL data from 953 donors show that the alternate allele at rs10814297 is associated with reduced SPAAR expression in tibial nerve, skeletal muscle, stomach, and esophagus muscularis, and with reduced expression of three additional nearby genes (identified by Ensembl IDs ENSG00000290538, ENSG00000287986, and ENSG00000304867) primarily in tibial nerve and subcutaneous adipose tissue GTEx Portal.
Reported associations
- Adult height: rs10814297 is among 12,111 SNPs significantly associated with height in a meta-analysis spanning European, East Asian, Hispanic, African, and South Asian ancestry groups; these SNPs collectively explain approximately 40% of phenotypic variance in European-ancestry populations and approximately 10-20% in other ancestries PMID 36224396.
- Multi-trait phenome-wide associations: The MVP atlas covering 2,068 traits identified 26,049 variant-trait associations across 1,270 traits, including 3,477 associations significant only after including participants from non-European ancestry groups; this locus falls within the broader landscape of catalogued associations PMID 38696054.
Evidence quality
The height association comes from one of the largest GWAS ever conducted, with 5.4 million participants across 281 studies and 12,111 genome-wide-significant SNPs that the authors describe as saturating the common-variant heritability map for height in European-ancestry populations PMID 36224396. The MVP study adds cross-ancestry depth with 635,969 participants, statistical fine-mapping to identify high-confidence causal variants, and detection of associations that emerge only with the inclusion of non-European populations PMID 38696054. The provided study text does not report a variant-specific effect size, odds ratio, or percentage of variance uniquely attributable to rs10814297, which limits quantitative interpretation of this locus in isolation. Prediction accuracy for height polygenic scores falls from approximately 40% of variance explained in European-ancestry populations to 10-20% in other groups, a gap attributed to differences in linkage disequilibrium (the tendency for nearby variants to be co-inherited) and allele frequency across populations, rather than different causal biology PMID 36224396.
Tissue-specific expression effects
- SPAAR: Reduced expression in tibial nerve (strongest effect observed across tissues), stomach, esophagus muscularis, and skeletal muscle GTEx Portal.
- ENSG00000290538 (nearby uncharacterized gene): Reduced expression in tibial nerve and subcutaneous adipose tissue GTEx Portal.
- ENSG00000287986 (nearby uncharacterized gene): Reduced expression in tibial nerve GTEx Portal.
- ENSG00000304867 (nearby uncharacterized gene): Reduced expression in tibial nerve GTEx Portal.
Lifestyle considerations
No lifestyle considerations on file for this variant.
Frequently asked questions
What does the SPAAR gene do?
SPAAR stands for Striated Muscle Activator of Rho Signaling and is involved in muscle development and signaling pathways. GTEx data show that rs10814297 is associated with reduced SPAAR expression in tissues including tibial nerve and skeletal muscle.
Is rs10814297 linked to height?
Yes. rs10814297 near SPAAR is among 12,111 SNPs identified as significantly associated with adult height in a meta-analysis of 5.4 million individuals. These SNPs collectively account for nearly all common-variant heritability of height.
How was rs10814297 discovered?
This variant was captured in large genome-wide association studies including the GIANT consortium height GWAS with 5.4 million participants across 281 studies, and the VA Million Veteran Program multi-trait GWAS with 635,969 participants from diverse ancestry groups.
Does rs10814297 affect gene expression?
GTEx v11 data from 953 donors show the alternate allele at rs10814297 is associated with reduced expression of SPAAR in tibial nerve, skeletal muscle, stomach, and esophagus muscularis. Three nearby uncharacterized genes also show reduced expression primarily in tibial nerve.
Does rs10814297 affect all ancestry groups equally?
Polygenic scores built from height-associated SNPs explain about 40% of height variance in European-ancestry populations but only 10-20% in other ancestries. Researchers attribute this gap to differences in linkage disequilibrium and allele frequency across populations, not to different underlying biology.