@article{73d919442d374a3ba98e8fbc590a8567,
title = "Multi-omics integration analysis identifies novel genes for alcoholism with potential overlap with neurodegenerative diseases",
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.",
author = "{The Collaborative Study on the Genetics of Alcoholism (COGA)} and Manav Kapoor and Chao, {Michael J.} and Johnson, {Emma C.} and Gloriia Novikova and Dongbing Lai and Meyers, {Jacquelyn L.} and Jessica Schulman and Nurnberger, {John I.} and Bernice Porjesz and Yunlong Liu and Victor Hesselbrock and Samual Kuperman and John Kramer and Chella Kamarajan and Ashwini Pandey and Laura Bierut and Rice, {John P.} and Bucholz, {Kathleen K.} and Marc Schuckit and Jay Tischfield and Andrew Brooks and Hart, {Ronald P.} and Laura Almasy and Danielle Dick and Jessica Salvatore and Paul Slesinger and Tatiana Foroud and Edenberg, {Howard J.} and Edoardo Marcora and Arpana Agrawal and Alison Goate",
note = "Funding Information: COGA: The Collaborative Study on the Genetics of Alcoholism (COGA), Principal Investigators B. Porjesz, V. Hesselbrock, T. Foroud; Scientific Director, A. Agrawal; Translational Director, D. Dick, includes 11 different centers: University of Connecticut (V. Hesselbrock); Indiana University (H.J. Edenberg, T. Foroud, J. Nurnberger Jr., Y. Liu); University of Iowa (S. Kuperman, J. Kramer); SUNY Downstate (B. Porjesz, J. Meyers, C. Kamarajan, A. Pandey); Washington University in St. Louis (L. Bierut, J. Rice, K. Bucholz, A. Agrawal); University of California at San Diego (M. Schuckit); Rutgers University (J. Tischfield, A. Brooks, R. Hart); The Children{\textquoteright}s Hospital of Philadelphia, University of Pennsylvania (L. Almasy); Virginia Commonwealth University (D. Dick, J. Salvatore); Icahn School of Medicine at Mount Sinai (A. Goate, M. Kapoor, P. Slesinger); and Howard University (D. Scott). Other COGA collaborators include: L. Bauer (University of Connecticut); L. Wetherill, X. Xuei, D. Lai, S. O{\textquoteright}Connor, M. Plawecki, S. Lourens (Indiana University); L. Acion (University of Iowa); G. Chan (University of Iowa; University of Connecticut); D.B. Chorlian, J. Zhang, S. Kinreich, G. Pandey (SUNY Downstate); M. Chao (Icahn School of Medicine at Mount Sinai); A. Anokhin, V. McCutcheon, S. Saccone (Washington University); F. Aliev, P. Barr (Virginia Commonwealth University); H. Chin and A. Parsian are the NIAAA Staff Collaborators. We continue to be inspired by our memories of Henri Begleiter and Theodore Reich, founding PI and Co‐PI of COGA, and also owe a debt of gratitude to other past organizers of COGA, including Ting‐Kai Li, P. Michael Conneally, Raymond Crowe, Wendy Reich, and Robert E. Taylor, for their critical contributions. This national collaborative study is supported by NIH Grant U10AA008401 from the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and the National Institute on Drug Abuse (NIDA). The authors acknowledge the Office of Research Infrastructure of the National Institutes of Health under award numbers S10OD018522 and S10OD026880. Dr. Kapoor{\textquoteright}s also receives part of his salary from NIAAA funded R21 grant R21AA 026388. We also want to thank all investigators, volunteers, and participants of NSW Brain Tissue Resource Centre to provide the valuable brain samples of people with AUD and controls. Publisher Copyright: {\textcopyright} 2021, The Author(s).",
year = "2021",
month = dec,
day = "1",
doi = "10.1038/s41467-021-25392-y",
language = "English",
volume = "12",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}