Unraveling Neuro-Proteogenomic Landscape and Therapeutic Implications for Human Behaviors and Psychiatric Disorders.
Journal
Research square
Titre abrégé: Res Sq
Pays: United States
ID NLM: 101768035
Informations de publication
Date de publication:
31 Mar 2023
31 Mar 2023
Historique:
pubmed:
11
4
2023
medline:
11
4
2023
entrez:
10
4
2023
Statut:
epublish
Résumé
Understanding the genetic basis of neuro-related proteins is essential for dissecting the molecular basis of human behavioral traits and the disease etiology of neuropsychiatric disorders. Here, the SCALLOP Consortium conducted a genome-wide association meta-analysis of over 12,500 individuals for 184 neuro-related proteins in human plasma. The analysis identified 117 cis-regulatory protein quantitative trait loci (cis-pQTL) and 166 trans-pQTL. The mapped pQTL capture on average 50% of each protein's heritability. Mendelian randomization analyses revealed multiple proteins showing potential causal effects on neuro-related traits such as sleeping, smoking, feelings, alcohol intake, mental health, and psychiatric disorders. Integrating with established drug information, we validated 13 out of 13 matched combinations of protein targets and diseases or side effects with available drugs, while suggesting hundreds of re-purposing and new therapeutic targets. This consortium effort provides a large-scale proteogenomic resource for biomedical research on human behaviors and other neuro-related phenotypes.
Identifiants
pubmed: 37034613
doi: 10.21203/rs.3.rs-2720355/v1
pmc: PMC10081382
pii:
doi:
Types de publication
Preprint
Langues
eng
Déclaration de conflit d'intérêts
Competing interests statement P.R.H.J.T is a salaried employee of BioAge Labs, Inc. The remaining authors declare no competing financial interests. R.E.M has received a speaker fee from Illumina, is an advisor to the Epigenetic Clock Development Foundation, and a scientific consultant for Optima Partners. E.W. is now an employee of AstraZeneca.