Multi-ancestry transcriptome-wide association analyses yield insights into tobacco use biology and drug repurposing.

Autor:	Chen F; Department of Public Health Sciences, Penn State College of Medicine, Hershey, PA, USA., Wang X; Department of Public Health Sciences, Penn State College of Medicine, Hershey, PA, USA., Jang SK; Department of Psychology, University of Minnesota, Minneapolis, MN, USA., Quach BC; RTI International, Research Triangle, NC, USA., Weissenkampen JD; Department of Genetics, University of Pennsylvania, Philadelphia, PA, USA.; Department of Psychology, Penn State College of Medicine, Hershey, PA, USA., Khunsriraksakul C; Deparment of Bioinformatics and Genomics, Penn State College of Medicine, Hershey, PA, USA., Yang L; Department of Public Health Sciences, Penn State College of Medicine, Hershey, PA, USA., Sauteraud R; Department of Public Health Sciences, Penn State College of Medicine, Hershey, PA, USA., Albert CM; Department of Cardiology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.; Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, USA., Allred NDD; Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, USA., Arnett DK; College of Public Health, University of Kentucky, Lexington, KY, USA., Ashley-Koch AE; Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC, USA.; Department of Medicine, Duke University Medical Center, Durham, NC, USA.; Duke Comprehensive Sickle Cell Center, Duke University Medical Center, Durham, NC, USA., Barnes KC; Colorado Center for Personalized Medicine, University of Colorado Anschutz Medical Center, Aurora, CO, USA., Barr RG; Department of Medicine, Columbia University Medical Center, New York, NY, USA., Becker DM; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Bielak LF; Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA., Bis JC; Department of Medicine, Cardiovascular Health Research Unit, University of Washington, Seattle, WA, USA., Blangero J; Department of Human Genetics, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, USA.; South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, USA., Boorgula MP; Colorado Center for Personalized Medicine, University of Colorado Anschutz Medical Center, Aurora, CO, USA., Chasman DI; Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA., Chavan S; Colorado Center for Personalized Medicine, University of Colorado Anschutz Medical Center, Aurora, CO, USA., Chen YI; Department of Pediatrics, Institute for Translational Genomics and Population Sciences, Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA., Chuang LM; Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan., Correa A; Department of Medicine, Jackson Heart Study, University of Mississippi Medical Center, Jackson, MS, USA., Curran JE; Department of Human Genetics, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, USA.; South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, USA., David SP; University of Chicago, Chicago, IL, USA.; NorthShore University Health System, Evanston, IL, USA., de las Fuentes L; Department of Medicine, Division of Biostatistics and Cardiovascular Division, Washington University School of Medicine, St. Louis, MO, USA., Deka R; Department of Environmental and Public Health Sciences, College of Medicine, University of Cincinnati, Cincinnati, OH, USA., Duggirala R; Department of Human Genetics, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, USA.; South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, USA., Faul JD; Institute for Social Research, Survey Research Center, University of Michigan, Ann Arbor, MI, USA., Garrett ME; Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC, USA.; Department of Medicine, Duke University Medical Center, Durham, NC, USA., Gharib SA; Department of Medicine, Cardiovascular Health Research Unit, University of Washington, Seattle, WA, USA.; Computational Medicine Core at Center for Lung Biology, Division of Pulmonary, Critical Care and Sleep Medicine, University of Washington, Seattle, WA, USA., Guo X; Department of Pediatrics, Institute for Translational Genomics and Population Sciences, Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA., Hall ME; Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA., Hawley NL; Department of Epidemiology (Chronic Disease), School of Public Health, Yale University, New Haven, CT, USA., He J; Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA., Hobbs BD; Harvard Medical School, Boston, MA, USA.; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA, USA., Hokanson JE; Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Hsiung CA; Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan., Hwang SJ; The Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.; The Framingham Heart Study, Framingham, MA, USA., Hyde TM; Lieber Institute for Brain Development, Baltimore, MD, USA.; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Irvin MR; Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA., Jaffe AE; Lieber Institute for Brain Development, Baltimore, MD, USA.; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Department of Mental Health and Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.; Department of Human Genetics and Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Johnson EO; RTI International, Research Triangle, NC, USA., Kaplan R; Department of Epidemiology and Population Health, Albert Einstein College of Medicine, The Bronx, NY, USA.; Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA., Kardia SLR; Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA., Kaufman JD; Departments of Environmental & Occupational Health Sciences, Medicine, and Epidemiology, University of Washington Seattle, Seattle, WA, USA., Kelly TN; Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA., Kleinman JE; Lieber Institute for Brain Development, Baltimore, MD, USA.; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Kooperberg C; Fred Hutchinson Cancer Center, Seattle, WA, USA., Lee IT; Department of Internal Medicine, Division of Endocrinology and Metabolism, Taichung Veterans General Hospital, Taichung, Taiwan., Levy D; The Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA., Lutz SM; Department of Population Medicine, Harvard Pilgrim Health Care, Boston, MA, USA., Manichaikul AW; Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA., Martin LW; Division of Cardiology, George Washington University School of Medicine and Health Sciences, Washington, DC, USA., Marx O; Department of Biomedical Sciences, Penn State College of Medicine, Hershey, PA, USA., McGarvey ST; Department of Epidemiology, International Health Institute, Brown University School of Public Health, Providence, RI, USA., Minster RL; Department of Human Genetics and Department of Biostatistics, University of Pittsburgh, Pittsburgh, PA, USA., Moll M; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA, USA., Moussa KA; Penn State Huck Institutes of Life Sciences, Penn State College of Medicine, University Park, PA, USA., Naseri T; Ministry of Health, Government of Samoa, Apia, Samoa., North KE; Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Oelsner EC; Department of Medicine, Columbia University Medical Center, New York, NY, USA., Peralta JM; Department of Human Genetics, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, USA.; South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, USA., Peyser PA; Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA., Psaty BM; Department of Medicine, Cardiovascular Health Research Unit, University of Washington, Seattle, WA, USA.; Department of Epidemiology, University of Washington, Seattle, WA, USA.; Department of Health Systems and Population Health, University of Washington, Seattle, WA, USA., Rafaels N; Colorado Center for Personalized Medicine, University of Colorado Anschutz Medical Center, Aurora, CO, USA., Raffield LM; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Reupena MS; Lutia I Puava Ae Mapu I Fagalele, Apia, Samoa., Rich SS; Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA., Rotter JI; Department of Pediatrics, Institute for Translational Genomics and Population Sciences, Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA., Schwartz DA; Department of Medicine, University of Colorado, Aurora, CO, USA., Shadyab AH; Herbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, La Jolla, CA, USA., Sheu WH; Taipei Veterans General Hospital, Taipei, Taiwan., Sims M; Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA., Smith JA; Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.; Institute for Social Research, Survey Research Center, University of Michigan, Ann Arbor, MI, USA., Sun X; Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA., Taylor KD; Department of Pediatrics, Institute for Translational Genomics and Population Sciences, Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA., Telen MJ; Department of Medicine, Duke University Medical Center, Durham, NC, USA., Watson H; Faculty of Medical Sciences, University of the West Indies, Cave Hill Campus, Barbados., Weeks DE; Department of Human Genetics and Department of Biostatistics, University of Pittsburgh, Pittsburgh, PA, USA., Weir DR; Institute for Social Research, Survey Research Center, University of Michigan, Ann Arbor, MI, USA., Yanek LR; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Young KA; Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Young KL; Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Zhao W; Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.; Institute for Social Research, Survey Research Center, University of Michigan, Ann Arbor, MI, USA., Hancock DB; RTI International, Research Triangle, NC, USA., Jiang B; Department of Public Health Sciences, Penn State College of Medicine, Hershey, PA, USA. bjiang@phs.psu.edu., Vrieze S; Department of Psychology, University of Minnesota, Minneapolis, MN, USA. vrieze@umn.edu., Liu DJ; Department of Public Health Sciences, Penn State College of Medicine, Hershey, PA, USA. dajiang.liu@psu.edu.
Jazyk:	angličtina
Zdroj:	Nature genetics [Nat Genet] 2023 Feb; Vol. 55 (2), pp. 291-300. Date of Electronic Publication: 2023 Jan 26.
DOI:	10.1038/s41588-022-01282-x
Abstrakt:	Most transcriptome-wide association studies (TWASs) so far focus on European ancestry and lack diversity. To overcome this limitation, we aggregated genome-wide association study (GWAS) summary statistics, whole-genome sequences and expression quantitative trait locus (eQTL) data from diverse ancestries. We developed a new approach, TESLA (multi-ancestry integrative study using an optimal linear combination of association statistics), to integrate an eQTL dataset with a multi-ancestry GWAS. By exploiting shared phenotypic effects between ancestries and accommodating potential effect heterogeneities, TESLA improves power over other TWAS methods. When applied to tobacco use phenotypes, TESLA identified 273 new genes, up to 55% more compared with alternative TWAS methods. These hits and subsequent fine mapping using TESLA point to target genes with biological relevance. In silico drug-repurposing analyses highlight several drugs with known efficacy, including dextromethorphan and galantamine, and new drugs such as muscle relaxants that may be repurposed for treating nicotine addiction. (© 2023. The Author(s).)
Databáze:	MEDLINE
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