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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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