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Expanding the genetic architecture of nicotine dependence and its shared genetics with multiple traits

Author

Listed:
  • Bryan C. Quach

    (GenOmics, Bioinformatics, and Translational Research Center, Biostatistics and Epidemiology Division, RTI International)

  • Michael J. Bray

    (Washington University)

  • Nathan C. Gaddis

    (GenOmics, Bioinformatics, and Translational Research Center, Biostatistics and Epidemiology Division, RTI International)

  • Mengzhen Liu

    (University of Minnesota Twin Cities)

  • Teemu Palviainen

    (Institute for Molecular Medicine Finland (FIMM), University of Helsinki)

  • Camelia C. Minica

    (Vrije Universiteit)

  • Stephanie Zellers

    (University of Minnesota Twin Cities)

  • Richard Sherva

    (Boston University School of Medicine)

  • Fazil Aliev

    (Virginia Commonwealth University
    Karabuk University)

  • Michael Nothnagel

    (Cologne Center for Genomics, University of Cologne
    University Hospital Cologne)

  • Kendra A. Young

    (University of Colorado Anschutz Medical Campus)

  • Jesse A. Marks

    (GenOmics, Bioinformatics, and Translational Research Center, Biostatistics and Epidemiology Division, RTI International)

  • Hannah Young

    (University of Minnesota Twin Cities)

  • Megan U. Carnes

    (GenOmics, Bioinformatics, and Translational Research Center, Biostatistics and Epidemiology Division, RTI International)

  • Yuelong Guo

    (GenOmics, Bioinformatics, and Translational Research Center, Biostatistics and Epidemiology Division, RTI International
    GeneCentric Therapeutics)

  • Alex Waldrop

    (GenOmics, Bioinformatics, and Translational Research Center, Biostatistics and Epidemiology Division, RTI International)

  • Nancy Y. A. Sey

    (University of North Carolina at Chapel Hill)

  • Maria T. Landi

    (National Cancer Institute, National Institutes of Health, United States Department of Health and Human Services)

  • Daniel W. McNeil

    (West Virginia University
    West Virginia University)

  • Dmitriy Drichel

    (Cologne Center for Genomics, University of Cologne
    University Hospital Cologne)

  • Lindsay A. Farrer

    (Boston University School of Medicine
    Boston University School of Medicine
    Boston University School of Medicine
    Boston University School of Public Health)

  • Christina A. Markunas

    (GenOmics, Bioinformatics, and Translational Research Center, Biostatistics and Epidemiology Division, RTI International)

  • Jacqueline M. Vink

    (Behavioural Science Institute, Radboud University)

  • Jouke-Jan Hottenga

    (Vrije Universiteit)

  • William G. Iacono

    (University of Minnesota Twin Cities)

  • Henry R. Kranzler

    (University of Pennsylvania Perelman School of Medicine
    VISN 4 MIRECC, Crescenz VA Medical Center)

  • Nancy L. Saccone

    (Washington University
    Washington University)

  • Michael C. Neale

    (Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University
    Virginia Commonwealth University)

  • Pamela Madden

    (Washington University)

  • Marcella Rietschel

    (Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg)

  • Mary L. Marazita

    (Center for Craniofacial and Dental Genetics, Department of Oral Biology, University of Pittsburgh)

  • Matthew McGue

    (University of Minnesota Twin Cities)

  • Hyejung Won

    (University of North Carolina at Chapel Hill)

  • Georg Winterer

    (Charité - University Medicine Berlin)

  • Richard Grucza

    (Saint Louis University)

  • Danielle M. Dick

    (Virginia Commonwealth University
    College Behavioral and Emotional Health Institute, Virginia Commonwealth University
    Virginia Commonwealth University)

  • Joel Gelernter

    (Yale University School of Medicine
    Yale University School of Medicine
    Yale University School of Medicine
    VA CT Healthcare Center)

  • Neil E. Caporaso

    (National Cancer Institute, National Institutes of Health, United States Department of Health and Human Services)

  • Timothy B. Baker

    (University of Wisconsin School of Medicine and Public Health)

  • Dorret I. Boomsma

    (Vrije Universiteit)

  • Jaakko Kaprio

    (Institute for Molecular Medicine Finland (FIMM), University of Helsinki
    University of Helsinki)

  • John E. Hokanson

    (University of Colorado Anschutz Medical Campus)

  • Scott Vrieze

    (University of Minnesota Twin Cities)

  • Laura J. Bierut

    (Washington University)

  • Eric O. Johnson

    (GenOmics, Bioinformatics, and Translational Research Center, Biostatistics and Epidemiology Division, RTI International
    Fellow Program, RTI International)

  • Dana B. Hancock

    (GenOmics, Bioinformatics, and Translational Research Center, Biostatistics and Epidemiology Division, RTI International)

Abstract

Cigarette smoking is the leading cause of preventable morbidity and mortality. Genetic variation contributes to initiation, regular smoking, nicotine dependence, and cessation. We present a Fagerström Test for Nicotine Dependence (FTND)-based genome-wide association study in 58,000 European or African ancestry smokers. We observe five genome-wide significant loci, including previously unreported loci MAGI2/GNAI1 (rs2714700) and TENM2 (rs1862416), and extend loci reported for other smoking traits to nicotine dependence. Using the heaviness of smoking index from UK Biobank (N = 33,791), rs2714700 is consistently associated; rs1862416 is not associated, likely reflecting nicotine dependence features not captured by the heaviness of smoking index. Both variants influence nearby gene expression (rs2714700/MAGI2-AS3 in hippocampus; rs1862416/TENM2 in lung), and expression of genes spanning nicotine dependence-associated variants is enriched in cerebellum. Nicotine dependence (SNP-based heritability = 8.6%) is genetically correlated with 18 other smoking traits (rg = 0.40–1.09) and co-morbidities. Our results highlight nicotine dependence-specific loci, emphasizing the FTND as a composite phenotype that expands genetic knowledge of smoking.

Suggested Citation

  • Bryan C. Quach & Michael J. Bray & Nathan C. Gaddis & Mengzhen Liu & Teemu Palviainen & Camelia C. Minica & Stephanie Zellers & Richard Sherva & Fazil Aliev & Michael Nothnagel & Kendra A. Young & Jes, 2020. "Expanding the genetic architecture of nicotine dependence and its shared genetics with multiple traits," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-19265-z
    DOI: 10.1038/s41467-020-19265-z
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