rs12285167 (DAGLA): Nerve & Liver Expression QTL

Key takeaways

• rs12285167 acts as an expression QTL (a variant that influences how much of a gene is produced in specific cells) in the DAGLA (Diacylglycerol Lipase Alpha) gene region, with the strongest signal in tibial nerve tissue (p=1.2e-11)
• The alternate allele is associated with increased DAGLA expression in tibial nerve and testis tissue
• The same variant increases MYRF (Myelin Regulatory Factor) expression in liver, whole blood, testis, and cultured fibroblasts, while simultaneously decreasing the neighboring antisense transcript MYRF-AS1 in liver by an equal magnitude
• A UK Biobank cohort study (n=92,246) found that metabolomic signatures of red and processed meat consumption were each independently associated with higher ischemic heart disease risk, with GWAS loci identified in lipid and lipoprotein metabolism; rs12285167 is not explicitly named in the provided study text

What the research says GTEx v11 eQTL (expression quantitative trait locus) data from 953 donors show that rs12285167 is associated with increased DAGLA expression in tibial nerve (slope +0.22, p=1.2e-11) and testis (slope +0.17, p=9.7e-7), all passing FDR (false discovery rate) less than 0.05 GTEx Portal. This variant is also an eQTL for two neighboring genes: MYRF shows increased expression in liver (slope +0.62, p=2.2e-10), testis (slope +0.24, p=3.6e-9), whole blood (slope +0.23, p=3.9e-10), and cultured fibroblasts (slope +0.16, p=1.7e-7), while MYRF-AS1, an antisense RNA gene on the complementary DNA strand, shows decreased liver expression of equal magnitude (slope -0.62, p=3.2e-7) GTEx Portal. A UK Biobank prospective cohort study (n=92,246, median follow-up 8.74 years, 3,059 incident ischemic heart disease events) built metabolomic signatures of red meat (157 metabolites) and processed meat (142 metabolites) consumption and found both positively associated with incident ischemic heart disease (IHD) - red meat signature: hazard ratio 1.11 per SD increment, 95% CI 1.06-1.16; processed meat signature: hazard ratio 1.16 per SD increment, 95% CI 1.11-1.21; both p<0.001 - with an accompanying GWAS identifying 45 loci (red meat) and 4 loci (processed meat) in lipid and lipoprotein metabolism, though rs12285167 is not explicitly named among these loci in the provided text.

Reported associations

• DAGLA expression - Tibial nerve: Alternate allele associated with increased expression (slope +0.22, p=1.2e-11, FDR<0.05) GTEx Portal
• DAGLA expression - Testis: Alternate allele associated with increased expression (slope +0.17, p=9.7e-7, FDR<0.05) GTEx Portal
• MYRF expression - Liver: Alternate allele associated with increased expression (slope +0.62, p=2.2e-10, FDR<0.05) GTEx Portal
• MYRF expression - Testis: Alternate allele associated with increased expression (slope +0.24, p=3.6e-9, FDR<0.05) GTEx Portal
• MYRF expression - Whole blood: Alternate allele associated with increased expression (slope +0.23, p=3.9e-10, FDR<0.05) GTEx Portal
• MYRF expression - Cultured fibroblasts: Alternate allele associated with increased expression (slope +0.16, p=1.7e-7, FDR<0.05) GTEx Portal
• MYRF-AS1 expression - Liver: Alternate allele associated with decreased expression (slope -0.62, p=3.2e-7, FDR<0.05), equal in magnitude but opposite in direction to the MYRF liver effect GTEx Portal
• Metabolomic signatures of meat consumption and IHD (observational context): A UK Biobank GWAS (n=92,246) identified 45 loci (red meat) and 4 loci (processed meat) in lipid and lipoprotein metabolism linked to IHD risk via metabolomic signatures; rs12285167 is not explicitly named as one of these loci in the provided source text

Evidence quality The eQTL evidence from GTEx v11 (953 donors, FDR<0.05) provides the most direct and explicit data for rs12285167, with highly significant p-values across multiple tissues and consistently positive effects on MYRF. The tibial nerve DAGLA signal (p=1.2e-11) is the strongest single-tissue association in the provided data. The UK Biobank IHD study (n=92,246) is large and prospectively designed, with both observational analyses (Cox proportional hazards) and Mendelian randomization (a genetic approach to infer causal relationships) converging on a link between meat-related metabolomic signatures and IHD risk; however, the provided study text lacks a PMID identifier and does not explicitly name rs12285167 as a discovered locus, making any direct connection between this variant and the IHD findings preliminary and inferential. The opposing MYRF and MYRF-AS1 expression directions in liver (both slope magnitude 0.62) are notable but their functional significance is not discussed in the provided sources. No conflicting findings are present within the provided data.

Tissue-specific expression effects

• DAGLA: Increased expression in tibial nerve and testis; the tibial nerve effect is the most significant eQTL signal for this gene reported in the provided data GTEx Portal
• MYRF: Increased expression in liver, testis, whole blood, and cultured fibroblasts; the liver effect is the largest across all tissues for this gene GTEx Portal
• MYRF-AS1: Reduced expression in liver, with an effect equal in magnitude but opposite in direction to the MYRF liver increase; this antisense transcript is transcribed from the complementary DNA strand overlapping MYRF GTEx Portal

Lifestyle considerations

• Unprocessed red meat (lifestyle, mixed, low): A UK Biobank cohort study found that metabolomic signatures reflecting red meat consumption were positively associated with ischemic heart disease risk, with GWAS loci identified in lipid metabolism; the direct role of rs12285167 in this pathway is not confirmed in the provided source.
• Processed meat (lifestyle, mixed, low): The same UK Biobank study found that metabolomic signatures of processed meat consumption showed a stronger association with ischemic heart disease risk (hazard ratio 1.16 per SD) than red meat signatures, with lipid and lipoprotein metabolism loci implicated; the role of rs12285167 specifically remains unconfirmed.