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

Quach, B.C.; Bray, M.J.; Gaddis, N.C.; Liu, M.; Palviainen, T.; Minica, C.C.; Zellers, S.; Sherva, R.; Aliev, F.; Nothnagel, M.; Young, K.A.; Marks, J.A.; Young, H.; Carnes, M.U.; Guo, Y.; Waldrop, A.; Sey, N..A.; Landi, M.T.; McNeil, D.W.; Drichel, D.; Farrer, L.A.; Markunas, C.A.; Vink, J.M.; Hottenga, J.J.; Iacono, W.G.; Kranzler, H.R.; Saccone, N.L.; Neale, M.C.; Madden, P.; Rietschel, M.; Marazita, M.L.; McGue, M.; Won, H.; Winterer, G.; Grucza, R.; Dick, D.M.; Gelernter, J.; Caporaso, N.E.; Baker, T.B.; Boomsma, D.I.; Kaprio, J.; Hokanson, J.E.; Vrieze, S.; Bierut, L.J.; Johnson, E.O.; Hancock, D.B.

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., Bray, M.J., Gaddis, N.C., Liu, M., Palviainen, T., Minica, C.C., Zellers, S., Sherva, R., Aliev, F., Nothnagel, M., Young, K.A., Marks, J.A., Young, H., Carnes, M.U., Guo, Y., Waldrop, A., Sey, N..A., Landi, M.T., McNeil, D.W., Drichel, D., Farrer, L.A., Markunas, C.A., Vink, J.M., Hottenga, J.J., Iacono, W.G., Kranzler, H.R., Saccone, N.L., Neale, M.C., Madden, P., Rietschel, M., Marazita, M.L., McGue, M., Won, H., Winterer, G., Grucza, R., Dick, D.M., Gelernter, J., Caporaso, N.E., Baker, T.B., Boomsma, D.I., Kaprio, J., Hokanson, J.E., Vrieze, S., Bierut, L.J., 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
ISSN:	2041-1723
Publisher:	Nature Publishing Group
Volume:	11
Number:	1
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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