Large‐scale pQTL analysis of over 3,000 CSF samples

Background Expression quantitative trait locus (eQTL) studies have been influential in identifying gene targets for many complex diseases. However, levels of mRNA often correlate poorly with the protein that they encode, due to rates degradation, translation, or alternative splicing, among other reasons. By correlating genetic variation, pQTLs can elucidate a more accurate architecture underlies disease. While few large-scale considered cerebrospinal fluid (CSF) levels, CSF biomarker are one primary diagnostic tools Alzheimer’s disease (AD), highlighting CSF’s relevance brain aging and AD pathology. Here, we present pQTL analysis over 3,000 individuals. Method We generated 7,584 analytes 3,065 samples using aptamer-based SOMAscan 7k platform. 4,884 additional 1,158 were also included. After stringent quality control, 3,107 unrelated European selected analysis. performed linear model as outcome variable, three-stage study design: discovery, replication, meta-analysis. colocalization our eQTLs GWAS loci, compared results from plasma identify CSF-specific pQTLs. used Mendelian Randomization (MR) proteins potentially causative traits. Result This represents first use platform CSF, well largest date. Of 3818 currently tested discovery set, 1480 at least SNP associated analyte level p < 5×10−8. Analyses ongoing. Conclusion previously 1.3k platform, where 425 identified 3 (PTP1B, Siglec-3, SLAF5) found through MR be involved risk, 48 associations neurodegenerative expands on those findings by including 6,000 much larger samples, allowing greater power. will vital novel drug disorders.