rs10993413 (AOPEP): Common Height-Associated Variant

Key takeaways

• rs10993413 near the AOPEP gene is one of thousands of common variants linked to adult human height identified in genetic research
• The finding comes from one of the largest genetic studies ever conducted, with 5.4 million participants across five ancestry groups
• All known common height variants together explain about 40 to 45 percent of height differences in people of European ancestry
• These same variants explain far less height variation in non-European populations, a recognized gap that ongoing research is working to close

What the research says rs10993413, near the AOPEP gene (aminopeptidase O), is among 12,111 independent common SNPs (single-nucleotide polymorphisms - positions in the genome where individuals commonly differ by a single DNA letter) found to be significantly associated with adult human height in a genome-wide association study (GWAS) of 5,380,080 individuals from five ancestry groups PMID 36224396. These 12,111 SNPs are distributed across 7,209 non-overlapping genomic segments covering roughly 21% of the human genome and together account for approximately 40% of height's phenotypic variance in populations of European ancestry, or about 45% when all HapMap 3 panel variants are included PMID 36224396. Prediction accuracy using these variants drops to 10-20% in non-European populations, a difference attributed to linkage disequilibrium (the tendency of nearby genetic variants to be inherited together) and differences in how common specific alleles are across ancestry groups PMID 36224396.

Reported associations

• Adult height: rs10993413 is one of 12,111 common genetic variants reaching genome-wide significance for adult height in a multi-ancestry meta-analysis of 5,380,080 participants from 281 studies; a specific per-SNP effect size for this individual variant was not reported in the provided study excerpt PMID 36224396.

Evidence quality Evidence for the height association at this locus comes from the largest height GWAS conducted to date, drawing on 5,380,080 individuals from 281 studies through the GIANT consortium and 23andMe, representing five major ancestry groups (approximately 76% European, 9% East Asian, 9% Hispanic, 6% African, and 1% South Asian) PMID 36224396. The study achieved near-saturation of common variant associations in European-ancestry populations, with the 12,111 identified SNPs accounting for nearly all common SNP-based heritability of height PMID 36224396. The authors noted that effect sizes and associated regions were broadly consistent across ancestries, and that reduced prediction accuracy in non-European groups is more likely explained by structural differences in the genome across populations than by distinct biological effects PMID 36224396. No separate replication study specific to rs10993413 is documented in the provided sources, and a per-SNP effect size for this variant was not available in the provided study text.

Lifestyle considerations No lifestyle considerations on file for this variant.