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

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, Jesse A. Marks, Hannah Young, Megan U. Carnes, Yuelong Guo, Alex Waldrop, Nancy Y. A. Sey, Maria T. Landi, Daniel W. McNeil, Dmitriy Drichel, Lindsay A. Farrer, Christina A. Markunas, Jacqueline M. Vink, Jouke-Jan Hottenga, William G. Iacono, Henry R. Kranzler, Nancy L. Saccone, Michael C. Neale, Pamela Madden, Marcella Rietschel, Mary L. Marazita, Matthew McGue, Hyejung Won, Georg Winterer, Richard Grucza, Danielle M. Dick, Joel Gelernter, Neil E. Caporaso, Timothy B. Baker, Dorret I. Boomsma, Jaakko Kaprio, John E. Hokanson, Scott Vrieze, Laura J. Bierut, Eric O. Johnson and Dana B. Hancock ()
Additional contact information
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
Michael Nothnagel: Cologne Center for Genomics, University of 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
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
Dmitriy Drichel: Cologne Center for Genomics, University of Cologne
Lindsay A. Farrer: Boston University School of Medicine
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
Nancy L. Saccone: Washington University
Michael C. Neale: Virginia Institute for Psychiatric and Behavioral Genetics, 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
Joel Gelernter: Yale University School of Medicine
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
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
Dana B. Hancock: GenOmics, Bioinformatics, and Translational Research Center, Biostatistics and Epidemiology Division, RTI International

Nature Communications, 2020, vol. 11, issue 1, 1-13

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-19265-z

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