ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2022
Integrating human brain proteomic data with genome-wide association study findings identifies novel brain proteins in substance use traits.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.
- Multi-ancestry meta-analysis of tobacco use disorder identifies 461 potential risk genes and reveals associations with multiple health outcomes.Nature human behaviour · 2024Pooled it
- Deciphering cell type-specific causal genetic effects on brain imaging-derived phenotypes and disorders with single-cell Mendelian randomization.PLoS computational biology · 2026Article
- Identification of Mood Disorders Causal Genes by Integrating the Brain Proteome and Transcriptome.Molecular neurobiology · 2025Article
- A multi-omics Mendelian randomization study identifies new therapeutic targets for alcohol use disorder and problem drinking.Nature human behaviour · 2025Article
- Statistically and functionally fine-mapped blood eQTLs and pQTLs from 1,405 humans reveal distinct regulation patterns and disease relevance.Nature genetics · 2024Article
- Proteome-wide mendelian randomization identifies causal plasma proteins in venous thromboembolism development.Journal of human genetics · 2023Article
- 5. Collaborative Study on the Genetics of Alcoholism: Functional genomics.Genes, brain, and behavior · 2023Review
- Multi-ancestry meta-analysis of tobacco use disorder prioritizes novel candidate risk genes and reveals associations with numerous health outcomes.medRxiv : the preprint server for health sciences · 2023Article
- Inter-Regional Proteomic Profiling of the Human Brain Using an Optimized Protein Extraction Method from Formalin-Fixed Tissue to Identify Signaling Pathways.International journal of molecular sciences · 2023Article
- Identifying Genes Associated with Alzheimer's Disease Using Gene-Based Polygenic Risk Score.Journal of Alzheimer's disease : JAD · 2023Article
- MicroRNA-mRNA networks are dysregulated in opioid use disorder postmortem brain: Further evidence for opioid-induced neurovascular alterations.Frontiers in psychiatry · 2022Article
- Peripheral signature of altered synaptic integrity in young onset cannabis use disorder: A proteomic study of circulating extracellular vesicles.The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological PsychiatryArticle
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Despite the identification of a growing number of genetic risk loci for substance use traits (SUTs), the impact of these loci on protein abundance and the potential utility of relevant proteins as therapeutic targets are unknown. We conducted a proteome-wide association study (PWAS) in which we integrated human brain proteomes from discovery (Banner; N = 152) and validation (ROSMAP; N = 376) datasets with genome-wide association study (GWAS) summary statistics for 4 SUTs. The 4 samples comprised GWAS of European-ancestry individuals for smoking initiation [Smk] (N = 1,232,091), alcohol use disorder [AUD] (N = 313,959), cannabis use disorder [CUD] (N = 384,032), and opioid use disorder [OUD] (N = 302,585). We conducted transcriptome-wide association studies (TWAS) with human brain transcriptomic data to examine the overlap of genetic effects at the proteomic and transcriptomic levels and characterize significant genes through conditional, colocalization, and fine-mapping analyses. We identified 27 genes (Smk = 21, AUD = 3, CUD = 2, OUD = 1) that were significantly associated with cis-regulated brain protein abundance. Of these, 7 showed evidence for causality (Smk: NT5C2, GMPPB, NQO1, RHOT2, SRR and ACTR1B; and AUD: CTNND1). Cis-regulated transcript levels for 8 genes (Smk = 6, CUD = 1, OUD = 1) were associated with SUTs, indicating that genetic loci could confer risk for these SUTs by modulating both gene expression and proteomic abundance. Functional studies of the high-confidence risk proteins identified here are needed to determine whether they are modifiable targets and useful in developing medications and biomarkers for these SUTs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.