Journal article
Multi-omics integration analysis identifies novel genes for alcoholism with potential overlap with neurodegenerative diseases
Nature communications, Vol.12(1), pp.5071-5071
08/20/2021
DOI: 10.1038/s41467-021-25392-y
PMCID: PMC8379159
PMID: 34417470
Abstract
Identification of causal variants and genes underlying genome-wide association study (GWAS) loci is essential to understand the biology of alcohol use disorder (AUD) and drinks per week (DPW). Multi-omics integration approaches have shown potential for fine mapping complex loci to obtain biological insights to disease mechanisms. In this study, we use multi-omics approaches, to fine-map AUD and DPW associations at single SNP resolution to demonstrate that rs56030824 on chromosome 11 significantly reduces SPI1 mRNA expression in myeloid cells and lowers risk for AUD and DPW. Our analysis also identifies MAPT as a candidate causal gene specifically associated with DPW. Genes prioritized in this study show overlap with causal genes associated with neurodegenerative disorders. Multi-omics integration analyses highlight, genetic similarities and differences between alcohol intake and disordered drinking, suggesting molecular heterogeneity that might inform future targeted functional and cross-species studies.
Alcohol use disorder and drinks per week both have been studied genetically and have different correlations with psychiatric diseases. Here the authors integrate multi-omics data to identify unique and shared variants, genes and pathways for alcohol use disorder and drinks per week.
Details
- Title: Subtitle
- Multi-omics integration analysis identifies novel genes for alcoholism with potential overlap with neurodegenerative diseases
- Creators
- Manav Kapoor - Icahn School of Medicine at Mount SinaiMichael Chao - Icahn School of Medicine at Mount SinaiEmma C. Johnson - Washington University in St. LouisGloriia Novikova - Icahn School of Medicine at Mount SinaiDongbing Lai - Indiana UniversityJacquelyn Meyers - SUNY Downstate Health Sciences UniversityJessica Schulman - Icahn School of Medicine at Mount SinaiJohn I Nurnberger Jr - Indiana UniversityBernice Porjesz - SUNY Downstate Health Sciences UniversityYunlong Liu - Indiana UniversityTatiana Foroud - Indiana UniversityHoward J. Edenberg - Indiana UniversityEdoardo Marcora - Icahn School of Medicine at Mount SinaiArpana Agrawal - Washington University in St. LouisAlison Goate - Icahn School of Medicine at Mount SinaiCollaborative Study on the Genetics of Alcoholism (COGA)
- Contributors
- Samuel Kuperman (Contributor) - University of Iowa, Psychiatry
- Resource Type
- Journal article
- Publication Details
- Nature communications, Vol.12(1), pp.5071-5071
- DOI
- 10.1038/s41467-021-25392-y
- PMID
- 34417470
- PMCID
- PMC8379159
- NLM abbreviation
- Nat Commun
- ISSN
- 2041-1723
- eISSN
- 2041-1723
- Publisher
- NATURE PORTFOLIO
- Number of pages
- 12
- Grant note
- R21AA 026388 / NIAAA; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Alcohol Abuse & Alcoholism (NIAAA) U10AA008401 / NIH from the National Institute on Alcohol Abuse and Alcoholism (NIAAA); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Alcohol Abuse & Alcoholism (NIAAA) U10AA008401 / NIH Grant from National Institute on Drug Abuse (NIDA) S10OD018522; S10OD026880 / Office of Research Infrastructure of the National Institutes of Health
- Language
- English
- Date published
- 08/20/2021
- Academic Unit
- Psychiatry
- Record Identifier
- 9984293752402771
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