rs10869719 (PCSK5): Adult Height Variant

Key takeaways

• rs10869719 is in the PCSK5 (Proprotein Convertase Subtilisin/Kexin Type 5) gene region and has been studied in connection with adult height in large-scale genetic research
• A 2022 genome-wide study of 5.4 million people found 12,111 common genetic variants significantly linked to height, with associated regions covering about 21% of the human genome
• Together, these height-associated variants account for about 40% of height differences in people of European ancestry, but only 10-20% in other ancestry groups
• The lower prediction accuracy in non-European populations likely reflects differences in how variants cluster together in different populations, not differences in underlying biology

What the research says A genome-wide association study (GWAS) - a method that systematically scans millions of DNA positions across large groups of people to find statistical links with a trait - of up to 5,380,080 individuals from 281 research studies identified 12,111 independent SNPs (single-nucleotide polymorphisms, or single-letter changes in the DNA sequence) significantly associated with adult height, clustered within 7,209 non-overlapping genomic segments averaging roughly 90 kilobases each and covering approximately 21% of the genome. In out-of-sample validation analyses, these 12,111 variants explained approximately 40% of height variation in European-ancestry populations (or 45% when all variants in the HapMap 3 reference panel are included), but only around 10-20% (or 14-24%) in other ancestry groups. The study further found that the biological pathways underlying height can be detected with smaller sample sizes than are needed to pinpoint individual causal genes, indicating that the broad genetic architecture of height is well-characterized even as specific variant-level mechanisms at many loci remain under active investigation.

Reported associations

• Adult height: This locus is among thousands of common variants studied in a GWAS of 5.4 million individuals for links to adult height; specific effect size or p-value data for rs10869719 individually are not described in the available study text, but the broader dataset found associations spanning about 21% of the genome that together explain roughly 40% of height variance in European-ancestry samples (n = up to 5,380,080)

Evidence quality The height GWAS providing context for this locus used up to 5,380,080 individuals across 281 studies, spanning five major ancestry groups: predominantly European (75.8%), East Asian (8.8%), Hispanic and admixed (8.5%), African (5.5%), and South Asian (1.4%). Out-of-sample prediction - testing whether the discovered variants actually predict height in independent samples - confirmed that the 12,111 variants explain about 40% of height variation in European-ancestry populations, validating the discovery findings. In non-European groups, out-of-sample prediction explained only 10-20%, a discrepancy the authors attributed to differences in linkage disequilibrium (the tendency of nearby DNA variants to be inherited together as a unit) and allele frequency patterns rather than differences in biological effect sizes. Effect sizes and associated regions are described as similar across ancestries. No specific replication statistics or effect size estimates for rs10869719 individually are provided in the available study text, limiting variant-level interpretation. No conflicting findings are noted within this study.

Lifestyle considerations No lifestyle considerations on file for this variant.