rs12135289 (RD3/SLC30A1): Height and Gene Expression
Key takeaways
- rs12135289 was identified in a 5.4 million-person study as a height-associated variant.
- The variant reduces expression of ENSG00000300476 in heart muscle tissue.
- It also reduces RD3 expression in the nucleus accumbens, a brain reward region.
- Height predictions based on this class of variants work better for European ancestry than for other ancestry groups.
Key takeaways
- rs12135289 was identified in a 5.4 million-person study as a height-associated variant.
- The variant reduces expression of ENSG00000300476 in heart muscle tissue.
- It also reduces RD3 expression in the nucleus accumbens, a brain reward region.
- Height predictions based on this class of variants work better for European ancestry than for other ancestry groups.
What the research says A genome-wide association study of 5,380,080 individuals from 281 studies identified 12,111 independent SNPs significantly associated with adult height, clustered within 7,209 non-overlapping genomic segments covering approximately 21% of the genome; rs12135289 falls within this mapped set of height-associated regions. In tissue-specific expression analysis, the ALT allele at this locus is associated with reduced expression of ENSG00000300476 in heart left ventricle tissue (p=1.5e-5) and heart atrial appendage tissue (p=1.4e-4), and with reduced expression of RD3 in the nucleus accumbens (p=3.7e-6) GTEx Portal.
Reported associations
- Adult height: A meta-analysis of 5,380,080 individuals identified 12,111 height-associated SNPs in this and other genomic regions, which collectively explain approximately 40% of phenotypic variance in European-ancestry populations (up to 45% when all HapMap 3 panel SNPs are included).
- ENSG00000300476 expression (heart): The ALT allele is associated with reduced expression in heart atrial appendage tissue (p=1.4e-4) and left ventricle tissue (p=1.5e-5) GTEx Portal.
- RD3 expression (brain): The ALT allele is associated with reduced expression of RD3 in the nucleus accumbens, a region of the basal ganglia (p=3.7e-6) GTEx Portal.
Evidence quality The height association is drawn from a large-scale meta-analysis (n=5,380,080) spanning individuals of European (approximately 76%), East Asian (approximately 9%), Hispanic (approximately 9%), African (approximately 6%), and South Asian (approximately 1%) ancestries. The study notes that prediction accuracy is substantially lower in non-European populations, attributed to differences in allele frequencies and linkage disequilibrium (the tendency for nearby genetic variants to be inherited together) across populations. The GTEx eQTL evidence is based on 953 donors at FDR less than 0.05, with the strongest signal for RD3 in the nucleus accumbens (p=3.7e-6), followed by ENSG00000300476 in left ventricle (p=1.5e-5) and atrial appendage (p=1.4e-4) GTEx Portal. No conflicting findings were identified across the provided data.
Tissue-specific expression effects
- ENSG00000300476: The ALT allele is associated with reduced expression in heart atrial appendage tissue and heart left ventricle tissue GTEx Portal.
- RD3: The ALT allele is associated with reduced expression in the nucleus accumbens (basal ganglia) of the brain GTEx Portal.
Lifestyle considerations No lifestyle considerations on file for this variant.
Frequently asked questions
What genes are near rs12135289?
rs12135289 is located near two genes: RD3 and SLC30A1. Gene expression studies show that the variant reduces expression of a nearby gene (ENSG00000300476) in heart tissue and reduces RD3 expression in a brain region called the nucleus accumbens.
Is rs12135289 linked to height?
Yes. A genome-wide study of more than 5.4 million people found this variant's region is associated with human height. The 12,111 height-related variants identified in that study collectively explain about 40-45% of height variation in European-ancestry populations.
What does rs12135289 do in the heart?
GTEx expression data shows that the ALT allele at rs12135289 is associated with reduced expression of a nearby gene (ENSG00000300476) in both the heart atrial appendage and left ventricle. The clinical significance of this expression change has not been established by the provided research.
What is the RD3 gene and how does this variant affect it?
The provided data identifies RD3 as a gene whose expression is reduced by the ALT allele of rs12135289 in the nucleus accumbens region of the brain. The provided studies do not describe RD3's biological function in detail.
Does rs12135289 affect all ancestries equally?
The large height study found that predictions based on height-associated variants explain about 40-45% of height variation in European-ancestry populations but are less accurate in East Asian, African, Hispanic, and South Asian ancestry groups, because the patterns of genetic variation differ across populations.