rs10744637 (CCND2-AS1): Height-Associated Variant
Key takeaways
- rs10744637 is located near HSPA8P5 (a pseudogene) and CCND2-AS1 (a long non-coding RNA) and is associated with adult height.
- It is one of 12,111 common variants found in a study of 5.4 million people that collectively account for nearly all common genetic heritability of height.
- These 12,111 variants together explain about 40% of height variation in European-ancestry populations, rising to 45% with a broader panel of common variants.
- Prediction accuracy using these variants is substantially lower in non-European populations (10-24%), underscoring the need for more ancestry-diverse genetic research.
Key takeaways
- rs10744637 is located near HSPA8P5 (a pseudogene, meaning a non-functional copy of a heat-shock protein gene) and CCND2-AS1 (a long non-coding RNA near the cyclin D2 gene) and is associated with adult human height.
- It is one of 12,111 common genetic variants (single-nucleotide polymorphisms, or SNPs) identified in a genome-wide association study of 5.4 million people that together account for nearly all common-variant heritability of height.
- These 12,111 variants collectively explain about 40% of height variation in European-ancestry populations, or about 45% when expanded to all variants on the HapMap 3 reference panel.
- Prediction accuracy using these variants is substantially lower in non-European populations (roughly 10-24%), likely due to differences in linkage disequilibrium patterns and allele frequencies across ancestries.
What the research says
A genome-wide association study (GWAS) -- a method that scans the genome to find positions statistically linked to a trait -- of 5.4 million 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 human genome PMID 36224396. rs10744637, mapping to the HSPA8P5 - CCND2-AS1 locus, is among these height-associated variants; the density of independent associations varies across the genome and regions of increased density are enriched for biologically relevant genes PMID 36224396. The full set of 12,111 SNPs accounts for approximately 40% of phenotypic variance in height in European-ancestry samples (or 45% with all HapMap 3 panel variants), representing near-saturation of common-variant heritability for height in that ancestry group PMID 36224396.
Reported associations
- Adult human height: rs10744637 is among 12,111 common SNPs found to be significantly associated with adult height in a meta-analysis of 5.4 million individuals spanning five broad ancestry groups; a locus-specific effect size for this individual SNP is not reported in the available study text PMID 36224396.
Evidence quality
The source study (Yengo et al., Nature 2022) is one of the largest genetic analyses ever conducted, comprising 5.4 million individuals from 281 cohorts with representation across five broad ancestry groups: approximately 4.1 million predominantly European, 473,000 predominantly East Asian, 455,000 Hispanic/admixed, 294,000 predominantly African, and 78,000 predominantly South Asian PMID 36224396. The 12,111 identified SNPs met genome-wide significance thresholds and the authors describe the common-variant map as near-saturated for European-ancestry populations, meaning the vast majority of common height-linked regions in that group are likely captured PMID 36224396. A key limitation is that locus-specific effect size data for rs10744637 individually are not available in the provided study text; additionally, prediction accuracy is substantially lower in non-European ancestries, and the authors note that further research is needed to achieve equivalent coverage across all population groups PMID 36224396. No independent replication data specific to this locus are available in the provided study materials.
Lifestyle considerations
No lifestyle considerations on file for this variant.
Frequently asked questions
What is rs10744637 associated with?
rs10744637 is associated with adult human height. It was identified as one of 12,111 common genetic variants linked to height in a genome-wide study of 5.4 million people published in Nature in 2022.
What is CCND2-AS1?
CCND2-AS1 is a long non-coding RNA - a type of RNA molecule that does not produce a protein - located near the CCND2 gene, which plays a role in cell cycle regulation. Its specific function in height differences has not been fully characterized.
What is HSPA8P5?
HSPA8P5 is a pseudogene, meaning it is a non-functional genomic copy of the HSPA8 gene, which normally encodes a heat shock protein involved in protein folding and cellular stress responses. Its specific role in height variation is not characterized in the available study data.
How much does rs10744637 affect height?
The individual effect size for rs10744637 is not available from the provided study text. Collectively, the 12,111 height-associated SNPs from the same study explain about 40% of height variation in European-ancestry populations.
Is this height variant relevant to all ancestries?
Height associations were studied across multiple ancestry groups, but prediction accuracy using the identified variants is substantially lower in non-European populations - accounting for roughly 10-24% of height variation - compared to about 40-45% in European-ancestry groups. This difference is attributed to variation in linkage disequilibrium patterns and allele frequencies.