Multi-omics integration analysis identifies novel genes for alcoholism with potential overlap with neurodegenerative diseases

Manav Kapoor (), Michael J. Chao, Emma C. Johnson, Gloriia Novikova, Dongbing Lai, Jacquelyn L. Meyers, Jessica Schulman, John I. Nurnberger, Bernice Porjesz, Yunlong Liu, Tatiana Foroud, Howard J. Edenberg, Edoardo Marcora, Arpana Agrawal and Alison Goate ()
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Manav Kapoor: Icahn School of Medicine at Mount Sinai
Michael J. Chao: Icahn School of Medicine at Mount Sinai
Emma C. Johnson: Washington University School of Medicine
Gloriia Novikova: Icahn School of Medicine at Mount Sinai
Dongbing Lai: Indiana University School of Medicine
Jacquelyn L. Meyers: State University of New York, Downstate Medical Center
Jessica Schulman: Icahn School of Medicine at Mount Sinai
John I. Nurnberger: Indiana University School of Medicine
Bernice Porjesz: State University of New York, Downstate Medical Center
Yunlong Liu: Indiana University School of Medicine
Tatiana Foroud: Indiana University School of Medicine
Howard J. Edenberg: Indiana University School of Medicine
Edoardo Marcora: Icahn School of Medicine at Mount Sinai
Arpana Agrawal: Washington University School of Medicine
Alison Goate: Icahn School of Medicine at Mount Sinai

Nature Communications, 2021, vol. 12, issue 1, 1-12

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-25392-y

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