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

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Item Type:Article
Title:Expanding the genetic architecture of nicotine dependence and its shared genetics with multiple traits
Creators Name:Quach, B.C. and Bray, M.J. and Gaddis, N.C. and Liu, M. and Palviainen, T. and Minica, C.C. and Zellers, S. and Sherva, R. and Aliev, F. and Nothnagel, M. and Young, K.A. and Marks, J.A. and Young, H. and Carnes, M.U. and Guo, Y. and Waldrop, A. and Sey, N..A. and Landi, M.T. and McNeil, D.W. and Drichel, D. and Farrer, L.A. and Markunas, C.A. and Vink, J.M. and Hottenga, J.J. and Iacono, W.G. and Kranzler, H.R. and Saccone, N.L. and Neale, M.C. and Madden, P. and Rietschel, M. and Marazita, M.L. and McGue, M. and Won, H. and Winterer, G. and Grucza, R. and Dick, D.M. and Gelernter, J. and Caporaso, N.E. and Baker, T.B. and Boomsma, D.I. and Kaprio, J. and Hokanson, J.E. and Vrieze, S. and Bierut, L.J. and Johnson, E.O. and Hancock, D.B.
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 (r(g) = 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.
Keywords:Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Heritable Quantitative Trait, Inheritance Patterns, Linkage Disequilibrium, Meta-Analysis as Topic, Molecular Sequence Annotation, Phenotype, Single Nucleotide Polymorphism, Tobacco Use Disorder
Source:Nature Communications
Publisher:Nature Publishing Group
Page Range:5562
Date:3 November 2020
Official Publication:https://doi.org/10.1038/s41467-020-19265-z
PubMed:View item in PubMed

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