rs11204264 (GDF10): Height-Associated Genetic Variant

Key takeaways

• Found among 12,111 height-linked variants in the largest height genetics study ever conducted, covering 5.4 million people across five ancestry groups
• Located near GDF10 (Growth Differentiation Factor 10), a bone morphogenetic protein family member with roles in skeletal development
• The alternate allele increases SYT15B expression in multiple brain reward regions (nucleus accumbens, caudate, amygdala), as well as in aorta and thyroid
• All 12,111 identified height variants together explain roughly 40% of height variation in European-ancestry populations and 10-20% in other ancestries
• Individual per-SNP effects on height are very small, reflecting the highly polygenic (many-gene) nature of height as a trait

What the research says rs11204264 is a common single-nucleotide polymorphism (SNP - a single-letter difference at a specific genomic position) located near PTPN20 (Protein Tyrosine Phosphatase Non-receptor Type 20) and GDF10 (Growth Differentiation Factor 10), a bone morphogenetic protein (BMP) family member with roles in skeletal development. It was identified as one of 12,111 independent SNPs significantly associated with adult height in a genome-wide meta-analysis (a pooled statistical analysis combining many studies) of 5,380,080 individuals from 281 studies spanning five major ancestry groups. Together, these 12,111 SNPs account for approximately 40% of the variance in adult height in European-ancestry populations and around 10-20% in populations of other ancestries, while all common variants in the HapMap 3 reference panel collectively explain 45% and 14-24%, respectively.

Reported associations

• Adult height: Identified as one of 12,111 independent SNPs significantly associated with adult height in a genome-wide meta-analysis of 5,380,080 participants of diverse ancestries; a specific per-SNP effect size for rs11204264 is not reported in the provided source material

Evidence quality The height association for rs11204264 derives from a single genome-wide meta-analysis with an exceptionally large sample (n = 5,380,080 across 281 studies), covering approximately 75.8% European, 8.8% East Asian, 8.5% Hispanic, 5.5% African, and 1.4% South Asian participants. The study authors note that effect sizes and associated genomic regions are similar across ancestries, but that prediction accuracy is substantially lower in non-European populations, likely because of differences in linkage disequilibrium (the tendency for nearby DNA variants to be co-inherited) and allele frequencies between groups. No specific p-value or per-SNP effect size for rs11204264 is reported in the provided source material. No conflicting findings are described in the provided evidence. Independent targeted replication of this specific variant is not described in the provided text, so its significance is best understood within the genome-wide statistical framework of a study of this scale rather than as a standalone finding.

Tissue-specific expression effects

• SYT15B (Synaptotagmin 15B, a gene involved in synaptic vesicle function): The alternate allele at this locus is linked to increased SYT15B expression in the nucleus accumbens basal ganglia, caudate basal ganglia, and amygdala (brain regions associated with reward and emotional processing), as well as in aorta, esophagus muscularis, and thyroid GTEx Portal
• ENSG00000309880 (an uncharacterized gene transcript): The alternate allele is linked to increased expression of this gene in the frontal cortex (Brodmann area 9, a region associated with executive function and decision-making) GTEx Portal
• BMS1P1 (BMS1 Ribosome Biogenesis Factor Pseudogene 1 - a pseudogene is a DNA sequence resembling a functional gene but not producing a known functional protein): The alternate allele is linked to increased BMS1P1 expression in testis GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.