rs112607667 (RAB37): Neurological Protein pQTL

Key takeaways

• rs112607667, near RAB37, was identified as influencing the blood levels of neurological proteins in a GWAS of 750 healthy older adults.
• The study found 41 genome-wide significant loci across 33 proteins using a strict significance threshold.
• Evidence is from a single discovery cohort; effect sizes may be overestimated and independent replication is needed.
• No lifestyle, dietary, or drug-response information is on record for this variant.

What the research says rs112607667 is located near RAB37 and was identified through a genome-wide association study (GWAS) of plasma levels of 92 neurological proteins (the Olink neurology panel) in 750 healthy older adults from the Lothian Birth Cohort 1936, a Scottish longitudinal ageing study, with participants having a mean age of approximately 73 years and protein levels adjusted for age, sex, population structure, and array plate. Across all 92 proteins tested, 41 independent genome-wide significant loci were identified for 33 proteins using a Bonferroni-corrected significance threshold of P < 5.4 x 10-10; the specific protein whose plasma level is associated with this locus, and its effect size, are not stated in the available study text. The study also integrated epigenome-wide association data and applied Mendelian randomisation - a statistical approach that uses genetic variants as proxies to test whether an association is likely causal rather than coincidental - to examine molecular mechanisms linking circulating protein levels to neurological disease states.

Reported associations

• Neurological protein plasma levels: rs112607667 was identified as a protein quantitative trait locus (pQTL) in a GWAS of 92 neurological proteins in 750 healthy older adults; the identity of the specific protein and its effect size are not available in the provided study text.
• Biological pathways: The full set of pQTLs identified in this study collectively implicate neurological, immunological, and extracellular matrix metabolic pathways as determined by functional enrichment analysis.

Evidence quality All evidence derives from a single discovery cohort of 750 healthy older adults in the Lothian Birth Cohort 1936, which is a modest sample size by current GWAS standards. The study authors explicitly noted that variance-explained estimates may be inflated owing to winner's curse or over-fitting in the discovery sample, a well-known issue in GWAS where the largest observed effect sizes tend to be overestimates. The applied significance threshold of P < 5.4 x 10-10 is a conservative Bonferroni correction across 92 proteins, which limits false positives. The replication status of this variant specifically is not described in the available study text. Findings should be considered preliminary.

Lifestyle considerations No lifestyle considerations on file for this variant.