The genetic landscape of neuro-related proteins in human plasma.

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.
Competing Interests: Competing interests P.R.H.J.T. is a salaried employee of BioAge Labs, Inc. R.E.M. has received a speaker fee from Illumina, is an advisor to the Epigenetic Clock Development Foundation and is a scientific consultant for Optima Partners. E.W. is now an employee of AstraZeneca. Y.S.A. is now an employee of GSK. A.S.B. has received grants from AstraZeneca, Bayer, Biogen, BioMarin and Sanofi. A.M. is an employee of Pfizer. X.S. is the founder of Quantix BioSciences and has received a speaker fee from Olink Proteomics. The remaining authors declare no competing interests.
(© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)