rs11185281 (SLC25A24): Height and Expression
Key takeaways
- One of 12,111 common SNPs linked to adult height, from the largest genetic study of height ever conducted, spanning 5.4 million people
- Located near SLC25A24, a gene that helps transport calcium and potassium across the inner membrane of mitochondria (the cell's energy-producing structures)
- The alternate allele is associated with increased SLC25A24 expression in cerebellar brain tissue but decreased expression in skin, esophageal tissue, and whole blood
- All 12,111 height-associated SNPs together explain about 40% of height variation in people of European ancestry, and less in other ancestry groups
Key takeaways
- One of 12,111 common SNPs linked to adult height, from the largest genetic study of height ever conducted, spanning 5.4 million people
- Located near SLC25A24, a gene that helps transport calcium and potassium across the inner membrane of mitochondria (the cell's energy-producing structures)
- The alternate allele is associated with increased SLC25A24 expression in cerebellar brain tissue but decreased expression in skin, esophageal tissue, and whole blood
- All 12,111 height-associated SNPs together explain about 40% of height variation in people of European ancestry, and less in other ancestry groups
What the research says rs11185281 lies near SLC25A24 (Solute Carrier Family 25 Member 24, which encodes a protein that transports calcium and potassium across the inner mitochondrial membrane) and was identified among 12,111 independent SNPs significantly associated with adult height in a genome-wide association study (GWAS, a large-scale statistical scan of millions of genetic variants across many people to find associations with a trait) of approximately 5.4 million individuals of diverse ancestries. These height-associated SNPs cluster in 7,209 non-overlapping genomic segments covering roughly 21% of the human genome, and collectively account for approximately 40% of height variation (or 45% when using the full HapMap 3 reference panel of common genetic variants) in European-ancestry populations. Their predictive power is substantially lower in non-European populations (roughly 10-20%, or 14-24% using the HapMap 3 panel), reflecting differences in linkage disequilibrium (the tendency for nearby genetic variants to be inherited together) and in allele frequency (how common specific variants are) across ancestry groups.
Reported associations
- Adult height: Identified as one of 12,111 independent SNPs significantly associated with adult height in a multi-ancestry GWAS of approximately 5.4 million individuals; individual SNP-level effect sizes for each of the 12,111 variants were not reported in the study abstract
- SLC25A24 expression, cerebellar brain: The alternate allele is associated with increased expression in the cerebellum and cerebellar hemisphere GTEx Portal
- SLC25A24 expression, peripheral tissues: The alternate allele is associated with decreased expression in esophageal mucosa, sun-exposed skin, non-sun-exposed skin, and whole blood GTEx Portal
- ENSG00000260879 expression, skin: The alternate allele is associated with decreased expression of a neighboring gene (ENSG00000260879) in both sun-exposed and non-sun-exposed skin GTEx Portal
Evidence quality The height association is derived from a GWAS of approximately 5.4 million individuals representing five broad ancestry groups (predominantly European, East Asian, Hispanic, African, and South Asian), making it the largest height genetics study reported to date. The 12,111 identified SNPs are predicted to account for nearly all common SNP-based heritability for height in European-ancestry populations, providing high confidence in the overall genetic map; however, individual effect sizes for each SNP were not reported in the available abstract, so the specific contribution of rs11185281 to height variation cannot be precisely quantified. Prediction accuracy is substantially lower in non-European populations (10-24% of height variation explained vs. 40-45% in European populations), and the authors note that equivalent coverage in other ancestries requires further research. The GTEx eQTL (expression quantitative trait locus, meaning a variant statistically linked to gene activity levels in a tissue) data from 953 donors, evaluated at a false discovery rate (FDR) threshold below 0.05, provide moderate-confidence evidence for tissue-specific regulatory effects on SLC25A24 and on the neighboring gene ENSG00000260879; these expression associations represent mechanistic context rather than confirmed causal pathways for the height association.
Tissue-specific expression effects
- SLC25A24: Increased expression in cerebellar and cerebellar hemisphere brain tissue; reduced expression in esophageal mucosa, sun-exposed skin, non-sun-exposed skin, and whole blood GTEx Portal
- ENSG00000260879: Reduced expression in sun-exposed and non-sun-exposed skin GTEx Portal
Lifestyle considerations No lifestyle considerations on file for this variant.
Frequently asked questions
What is SLC25A24?
SLC25A24 (Solute Carrier Family 25 Member 24) is a gene encoding a protein that transports calcium and small molecules across the inner membrane of mitochondria, the structures inside cells that produce energy. It plays a role in how cells regulate energy and calcium signaling.
Is rs11185281 linked to human height?
Yes. rs11185281, located near SLC25A24, is one of 12,111 common genetic variants identified as significantly associated with adult height in a genome-wide study of approximately 5.4 million people of diverse ancestries.
What does rs11185281 do to gene expression?
According to GTEx data from 953 tissue donors, the alternate allele at rs11185281 is associated with increased SLC25A24 expression in cerebellar brain tissue and decreased expression in skin, esophageal mucosa, and whole blood. These are mechanistic observations and do not by themselves explain the height association.
How much of height is explained by variants like rs11185281?
The 12,111 common height-associated SNPs as a group explain roughly 40-45% of height variation in people of European ancestry, and roughly 10-24% in other ancestry groups. No single variant accounts for a large fraction of that variation on its own.
Why is height prediction less accurate in non-European populations?
The height GWAS authors attribute lower prediction accuracy in non-European populations to differences in linkage disequilibrium (patterns of genetic variants being inherited together) and differences in how common specific variants are across ancestry groups. Further research in non-European populations is needed to close this gap.