ArticleNature genetics2023
Multi-ancestry transcriptome-wide association analyses yield insights into tobacco use biology and drug repurposing.
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Article in Nature genetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 3 of them syntheses that pooled it.
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39citing papers in PubMed, 3 pooled it
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Who cites it
39 citing papers in PubMed, 3 syntheses or guidelines pooled it.
- 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
- The landscape of the methodology in drug repurposing using human genomic data: a systematic review.Briefings in bioinformatics · 2024Pooled it
- Multi-ancestry and multi-trait genome-wide association meta-analyses inform clinical risk prediction for systemic lupus erythematosus.Nature communications · 2023Pooled it
- Multi-ancestry transcriptome-wide association study reveals shared and population-specific genetic effects in Alzheimer disease.American journal of human genetics · 2026Article
- Ancestral diversity in complex disease genetics: from discovery to translation.Nature reviews. Genetics · 2026Review
- scTWAS: a powerful statistical framework for single-cell transcriptome-wide association studies.Nature communications · 2026Article
- Review
- Integrating multi-omics and multi-context QTL data with GWAS reveals the genetic architecture of complex traits and improves the discovery of risk genes.medRxiv : the preprint server for health sciences · 2026Article
- Transcriptome-wide association studies at cell-state level using single-cell eQTL data.Cell genomics · 2026Article
- The China Brain Multi-omics Atlas Project (CBMAP).Molecular psychiatry · 2026Review
- Leveraging genomic and transcriptomic data of diverse ancestry to uncover mechanisms of psychiatric risk in the adult and developing brain.Nature communications · 2025Article
- Proteomic signatures of smoking and their associations with risk of incident diseases and mortality in diverse populations.Nature communications · 2025Article
- Integrating axis quantitative trait loci looks beyond cell types and offers insights into brain-related traits.Nature communications · 2025Article
- Unlocking biological insights from differentially expressed genes: Concepts, methods, and future perspectives.Journal of advanced research · 2025Review
- scTWAS: A powerful statistical framework for single-cell transcriptome-wide association studies.Research square · 2025Article
- Incorporating local ancestry information to predict genetically associated DNA methylation in admixed populations.Briefings in bioinformatics · 2025Observational
- An atlas of single-cell eQTLs dissects autoimmune disease genes and identifies novel drug classes for treatment.Cell genomics · 2025Article
- Genetically regulated eRNA expression predicts chromatin contact frequency and reveals genetic mechanisms at GWAS loci.Nature communications · 2025Article
- Enhancing nonlinear transcriptome- and proteome-wide association studies via trait imputation with applications to Alzheimer's disease.PLoS genetics · 2025Article
- Integrative genomics sheds light on the immunogenetics of tuberculosis in cattle.Communications biology · 2025Article
Corrections and comments
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Authors and funding
90 authors.
Fang Chen *Department of Public Health Sciences, Penn State College of Medicine, Hershey, PA, USA.ORCID http://orcid.org/0000-0003-3108-8204
Xingyan Wang *Department of Public Health Sciences, Penn State College of Medicine, Hershey, PA, USA.
Seon-Kyeong Jang *Department of Psychology, University of Minnesota, Minneapolis, MN, USA.
Bryan C QuachRTI International, Research Triangle, NC, USA.ORCID http://orcid.org/0000-0002-1094-3104
J Dylan WeissenkampenDepartment of Genetics, University of Pennsylvania, Philadelphia, PA, USA.
Chachrit KhunsriraksakulDeparment of Bioinformatics and Genomics, Penn State College of Medicine, Hershey, PA, USA.ORCID http://orcid.org/0000-0001-5131-1229
Lina YangDepartment of Public Health Sciences, Penn State College of Medicine, Hershey, PA, USA.
Renan SauteraudDepartment of Public Health Sciences, Penn State College of Medicine, Hershey, PA, USA.
Christine M AlbertDepartment of Cardiology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0002-2081-1121
Nicholette D D AllredDepartment of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, USA.ORCID http://orcid.org/0000-0001-8883-2511
Donna K ArnettCollege of Public Health, University of Kentucky, Lexington, KY, USA.ORCID http://orcid.org/0000-0003-2219-657X
Allison E Ashley-KochDuke Molecular Physiology Institute, Duke University Medical Center, Durham, NC, USA.ORCID http://orcid.org/0000-0001-5409-9155
Kathleen C BarnesColorado Center for Personalized Medicine, University of Colorado Anschutz Medical Center, Aurora, CO, USA.ORCID http://orcid.org/0000-0002-3030-4705
R Graham BarrDepartment of Medicine, Columbia University Medical Center, New York, NY, USA.
Diane M BeckerDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Lawrence F BielakDepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0002-3443-8030
Joshua C BisDepartment of Medicine, Cardiovascular Health Research Unit, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-3409-1110
John BlangeroDepartment of Human Genetics, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, USA.ORCID http://orcid.org/0000-0001-6250-5723
Meher Preethi BoorgulaColorado Center for Personalized Medicine, University of Colorado Anschutz Medical Center, Aurora, CO, USA.
Daniel I ChasmanDivision of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, USA.ORCID http://orcid.org/0000-0003-3357-0862
Sameer ChavanColorado Center for Personalized Medicine, University of Colorado Anschutz Medical Center, Aurora, CO, USA.ORCID http://orcid.org/0000-0002-0220-0845
Yii-Der I ChenDepartment of Pediatrics, Institute for Translational Genomics and Population Sciences, Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
Lee-Ming ChuangDepartment of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.ORCID http://orcid.org/0000-0003-0978-2662
Adolfo CorreaDepartment of Medicine, Jackson Heart Study, University of Mississippi Medical Center, Jackson, MS, USA.ORCID http://orcid.org/0000-0002-9501-600X
Joanne E CurranDepartment of Human Genetics, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, USA.ORCID http://orcid.org/0000-0002-6898-155X
Sean P DavidUniversity of Chicago, Chicago, IL, USA.
Lisa de las FuentesDepartment of Medicine, Division of Biostatistics and Cardiovascular Division, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0002-4689-325X
Ranjan DekaDepartment of Environmental and Public Health Sciences, College of Medicine, University of Cincinnati, Cincinnati, OH, USA.
Ravindranath DuggiralaDepartment of Human Genetics, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, USA.
Jessica D FaulInstitute for Social Research, Survey Research Center, University of Michigan, Ann Arbor, MI, USA.
Melanie E GarrettDuke Molecular Physiology Institute, Duke University Medical Center, Durham, NC, USA.ORCID http://orcid.org/0000-0003-2302-6150
Sina A GharibDepartment of Medicine, Cardiovascular Health Research Unit, University of Washington, Seattle, WA, USA.
Xiuqing GuoDepartment of Pediatrics, Institute for Translational Genomics and Population Sciences, Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.ORCID http://orcid.org/0000-0002-5264-5068
Michael E HallDepartment of Medicine, University of Mississippi Medical Center, Jackson, MS, USA.
Nicola L HawleyDepartment of Epidemiology (Chronic Disease), School of Public Health, Yale University, New Haven, CT, USA.ORCID http://orcid.org/0000-0002-2601-3454
Jiang HeDepartment of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA.
Brian D HobbsHarvard Medical School, Boston, MA, USA.
John E HokansonDepartment of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Chao A HsiungInstitute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan.
Shih-Jen HwangThe Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Thomas M HydeLieber Institute for Brain Development, Baltimore, MD, USA.ORCID http://orcid.org/0000-0002-8746-3037
Marguerite R IrvinDepartment of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA.
Andrew E JaffeLieber Institute for Brain Development, Baltimore, MD, USA.
Eric O JohnsonRTI International, Research Triangle, NC, USA.ORCID http://orcid.org/0000-0002-8870-1949
Robert KaplanDepartment of Epidemiology and Population Health, Albert Einstein College of Medicine, The Bronx, NY, USA.
Sharon L R KardiaDepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
Joel D KaufmanDepartments of Environmental & Occupational Health Sciences, Medicine, and Epidemiology, University of Washington Seattle, Seattle, WA, USA.
Tanika N KellyDepartment of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA.
Joel E KleinmanLieber Institute for Brain Development, Baltimore, MD, USA.ORCID http://orcid.org/0000-0002-4210-6052
Charles KooperbergFred Hutchinson Cancer Center, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-7986-8560
I-Te LeeDepartment of Internal Medicine, Division of Endocrinology and Metabolism, Taichung Veterans General Hospital, Taichung, Taiwan.
Daniel LevyThe Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0003-1843-8724
Sharon M LutzDepartment of Population Medicine, Harvard Pilgrim Health Care, Boston, MA, USA.
Ani W ManichaikulCenter for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.
Lisa W MartinDivision of Cardiology, George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
Olivia MarxDepartment of Biomedical Sciences, Penn State College of Medicine, Hershey, PA, USA.
Stephen T McGarveyDepartment of Epidemiology, International Health Institute, Brown University School of Public Health, Providence, RI, USA.ORCID http://orcid.org/0000-0003-1233-6970
Ryan L MinsterDepartment of Human Genetics and Department of Biostatistics, University of Pittsburgh, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0001-7382-6717
Matthew MollChanning Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Karine A MoussaPenn State Huck Institutes of Life Sciences, Penn State College of Medicine, University Park, PA, USA.
Take NaseriMinistry of Health, Government of Samoa, Apia, Samoa.
Kari E NorthDepartment of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID http://orcid.org/0000-0002-8903-0366
Elizabeth C OelsnerDepartment of Medicine, Columbia University Medical Center, New York, NY, USA.ORCID http://orcid.org/0000-0002-7481-9671
Juan M PeraltaDepartment of Human Genetics, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, USA.ORCID http://orcid.org/0000-0002-8811-5579
Patricia A PeyserDepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0002-9717-8459
Bruce M PsatyDepartment of Medicine, Cardiovascular Health Research Unit, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-7278-2190
Nicholas RafaelsColorado Center for Personalized Medicine, University of Colorado Anschutz Medical Center, Aurora, CO, USA.
Laura M RaffieldDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Muagututi'a Sefuiva ReupenaLutia I Puava Ae Mapu I Fagalele, Apia, Samoa.
Stephen S RichCenter for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.ORCID http://orcid.org/0000-0003-3872-7793
Jerome I RotterDepartment of Pediatrics, Institute for Translational Genomics and Population Sciences, Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
David A SchwartzDepartment of Medicine, University of Colorado, Aurora, CO, USA.ORCID http://orcid.org/0000-0001-6743-8443
Aladdin H ShadyabHerbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, La Jolla, CA, USA.
Wayne H-H SheuTaipei Veterans General Hospital, Taipei, Taiwan.
Mario SimsDepartment of Medicine, University of Mississippi Medical Center, Jackson, MS, USA.
Jennifer A SmithDepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0002-3575-5468
Xiao SunDepartment of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA.ORCID http://orcid.org/0000-0001-8802-2957
Kent D TaylorDepartment of Pediatrics, Institute for Translational Genomics and Population Sciences, Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
Marilyn J TelenDepartment of Medicine, Duke University Medical Center, Durham, NC, USA.
Harold WatsonFaculty of Medical Sciences, University of the West Indies, Cave Hill Campus, Barbados.
Daniel E WeeksDepartment of Human Genetics and Department of Biostatistics, University of Pittsburgh, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0001-9410-7228
David R WeirInstitute for Social Research, Survey Research Center, University of Michigan, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0002-1661-2402
Lisa R YanekDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID http://orcid.org/0000-0001-7117-1075
Kendra A YoungDepartment of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.ORCID http://orcid.org/0000-0002-8664-7635
Kristin L YoungDepartment of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID http://orcid.org/0000-0003-0070-6145
Wei ZhaoDepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0001-7388-0692
Dana B HancockRTI International, Research Triangle, NC, USA.ORCID http://orcid.org/0000-0003-2240-3604
Bibo JiangDepartment of Public Health Sciences, Penn State College of Medicine, Hershey, PA, USA. bjiang@phs.psu.edu.ORCID http://orcid.org/0000-0001-8336-9302
Scott VriezeDepartment of Psychology, University of Minnesota, Minneapolis, MN, USA. vrieze@umn.edu.ORCID http://orcid.org/0000-0003-3861-7930
Dajiang J LiuDepartment of Public Health Sciences, Penn State College of Medicine, Hershey, PA, USA. dajiang.liu@psu.edu.ORCID http://orcid.org/0000-0001-6553-858X
Funding
Women's Cancer Research ProgramP30CA014236 · NCI · DUKE UNIVERSITY · PI DONNA NIEDZWIECKI · 1985 to 2026
$174.8MYale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9MFramingham Project/LevyZIAHL006001 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI LEVY, DANIEL · 2009 to 2025
$51.1MXENOBIOTIC BIOTRANSFORMATION AND DISPOSITIONP30ES007033 · NIEHS · UNIVERSITY OF WASHINGTON · PI ALI SHOJAIE · 1995 to 2026
$42.5MPulmonary microvascular perfusion in the Multi-Ethnic Study of AtherosclerosisR01HL077612 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI R Graham BARR · 2004 to 2026
$18.8MPulmonary Vascular Changes in Early Chronic Obstructive Pulmonary Disease (COPD)R01HL093081 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI R Graham BARR · 2008 to 2026
$17.2MCHARGE Consortium: Omics Discovery for CVD and Aging PhenotypesR01HL105756 · NHLBI · UNIVERSITY OF WASHINGTON · PI Bruce M Psaty, NICHOLAS L SMITH · 2011 to 2026
$9.5MTranslational Research Training Program in Environmental Health SciencesT32ES019851 · NIEHS · UNIVERSITY OF PENNSYLVANIA · PI Kara A Bernstein, Trevor M Penning · 2012 to 2026
$6.0MMethods to unveil sex-specific genetic architecture in trans-ancestry meta-analysisR01HG011035 · NHGRI · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · PI Bibo Jiang · 2022 to 2026
$3.8MMulti-omic studies of asthma severity in an African ancestry populationR01AI132476 · NIAID · UNIVERSITY OF COLORADO DENVER · PI BARNES, KATHLEEN C, MATHIAS, RASIKA ANN · 2018 to 2022
$3.5MDeep Sequencing, Phenotyping, and Imputation in Large-Scale Biobanks: A Novel and Cost-Effective Framework to Identify Rare Mutations Associated with AddictionR01DA044283 · NIDA · UNIVERSITY OF MINNESOTA · PI ALBERT, FRANK WOLFGANG, VRIEZE, SCOTT IAN · 2019 to 2024
$3.2MMulti-omic Subtyping of Chronic Obstructive Pulmonary DiseaseK08HL136928 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI HOBBS, BRIAN DANIEL · 2017 to 2021
$864kNCATS NIH HHS UL1 TR001863NCI NIH HHS P30 CA014236NHGRI NIH HHS R01 HG011035NHGRI NIH HHS R56 HG011035NHGRI NIH HHS R56 HG012358NHLBI NIH HHS K08 HL136928NHLBI NIH HHS R01 HL077612NHLBI NIH HHS R01 HL093081NHLBI NIH HHS R01 HL105756NIAID NIH HHS R01 AI132476NIDA NIH HHS R01 DA044283NIEHS NIH HHS P30 ES007033NIEHS NIH HHS T32 ES019851NIH HHS R03 OD032630
Abstract
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.
Indexed as
Drug RepositioningTranscriptomeBiologyGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansPolymorphism, Single NucleotideTobacco Use
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