The genetic landscape of neuro-related proteins in human plasma.
Repetto L., Chen J., Yang Z., Zhai R., Timmers PRHJ., Feng X., Li T., Yao Y., Maslov D., Timoshchuk A., Tu F., Twait EL., May-Wilson S., Muckian MD., Prins BP., Png G., Kooperberg C., Johansson Å., Hillary RF., Wheeler E., Pan L., He Y., Klasson S., Ahmad S., Peters JE., Gilly A., Karaleftheri M., Tsafantakis E., Haessler J., Gyllensten U., Harris SE., Wareham NJ., Göteson A., Lagging C., Ikram MA., van Duijn CM., Jern C., Landén M., Langenberg C., Deary IJ., Marioni RE., Enroth S., Reiner AP., Dedoussis G., Zeggini E., Sharapov S., Aulchenko YS., Butterworth AS., Mälarstig A., Wilson JF., Navarro P., Shen X.
Understanding the genetic basis of neuro-related proteins is essential for dissecting the molecular basis of human behavioural traits and the disease aetiology of neuropsychiatric disorders. Here the SCALLOP Consortium conducted a genome-wide association meta-analysis of over 12,000 individuals for 184 neuro-related proteins in human plasma. The analysis identified 125 cis-regulatory protein quantitative trait loci (cis-pQTL) and 164 trans-pQTL. The mapped pQTL capture on average 50% of each protein's heritability. At the cis-pQTL, multiple proteins shared a genetic basis with human behavioural traits such as alcohol and food intake, smoking and educational attainment, as well as neurological conditions and psychiatric disorders such as pain, neuroticism and schizophrenia. Integrating with established drug information, the causal inference analysis validated 52 out of 66 matched combinations of protein targets and diseases or side effects with available drugs while suggesting hundreds of repurposing and new therapeutic targets.