rs11219666 (OR8A2P/OR8B9P): Metabolome GWAS Variant

Key takeaways

• rs11219666 sits near OR8A2P and OR8B9P, two non-functional copies (pseudogenes) of olfactory receptor genes on chromosome 11
• The alternate allele is associated with increased expression of a neighboring gene, OR8B10P, specifically in testis tissue
• This variant appeared in a genome-wide study of over 200 plasma metabolite levels conducted in the Framingham Heart Study
• No specific metabolite or disease association for this locus is detailed in the available study excerpts
• Current evidence is limited and preliminary, requiring replication in larger independent studies

What the research says A genome-wide association study (GWAS - a statistical scan of thousands of genetic variants for links to measured biological traits) of 217 plasma metabolites, encompassing both polar compounds and lipids, was conducted in 2,076 participants of the Framingham Heart Study, identifying 31 genetic loci significantly associated with circulating metabolite levels; for the majority of metabolites surveyed, the proportion of inter-individual variation explained by heritable factors exceeded that explained by measured clinical factors such as age, sex, and body-mass index. Gene expression data from GTEx v11 (953 donors, cis-window analysis, FDR<0.05) show that the alternate allele at rs11219666 is associated with increased expression of OR8B10P - a pseudogene in the same olfactory receptor gene cluster - specifically in testis tissue (eQTL slope +0.71, p=3.1×10^-6) GTEx Portal. The available study text does not specify which metabolite(s) the locus was associated with, so the precise biochemical pathway implicated cannot be described from the evidence at hand.

Reported associations

• Plasma metabolite levels: This locus was captured in a GWAS of 217 metabolites in 2,076 Framingham Heart Study participants; the study identified 31 genome-wide significant loci in total, but the specific metabolite association for rs11219666 is not described in the available study excerpt
• OR8B10P testis expression (eQTL): The alternate allele is associated with increased OR8B10P expression in testis tissue (slope +0.71, p=3.1×10^-6) GTEx Portal

Evidence quality The metabolome GWAS was conducted in 2,076 participants, a relatively modest sample by current GWAS standards, and no p-value or effect size specific to this variant's metabolite association appears in the available text. The GTEx eQTL result is drawn from 953 donors and passes a false discovery rate threshold below 5% (FDR<0.05), indicating moderate statistical confidence; the testis-specific signal (p=3.1×10^-6) is not reported in other tissues based on the available GTEx data, which limits mechanistic interpretation GTEx Portal. Overall, the evidence base for this variant is preliminary, and independent replication in larger cohorts would be needed before drawing firm conclusions about its biological role.

Tissue-specific expression effects

• OR8B10P: Increased expression in testis tissue associated with the alternate allele; no effect is reported in other tissues in the available GTEx data GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.