Quach, Bryan C., Bray, Michael J., Gaddis, Nathan C., Liu, Mengzhen, Palviainen, Teemu ORCID: 0000-0002-7847-8384, Minica, Camelia C., Zellers, Stephanie, Sherva, Richard, Aliev, Fazil ORCID: 0000-0001-8357-4699, Nothnagel, Michael, Young, Kendra A., Marks, Jesse A., Young, Hannah, Carnes, Megan U., Guo, Yuelong, Waldrop, Alex, Sey, Nancy Y. A., Landi, Maria T., McNeil, Daniel W., Drichel, Dmitriy, Farrer, Lindsay A., Markunas, Christina A., Vink, Jacqueline M., Hottenga, Jouke-Jan, Iacono, William G., Kranzler, Henry R., Saccone, Nancy L., Neale, Michael C., Madden, Pamela, Rietschel, Marcella, Marazita, Mary L., McGue, Matthew, Won, Hyejung, Winterer, Georg, Grucza, Richard, Dick, Danielle M., Gelernter, Joel, Caporaso, Neil E., Baker, Timothy B., Boomsma, Dorret I., Kaprio, Jaakko ORCID: 0000-0002-3716-2455, Hokanson, John E., Vrieze, Scott, Bierut, Laura J., Johnson, Eric O. and Hancock, Dana B. (2020). Expanding the genetic architecture of nicotine dependence and its shared genetics with multiple traits. Nat. Commun., 11 (1). BERLIN: NATURE RESEARCH. ISSN 2041-1723

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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 Fagerstrom 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. There is strong genetic evidence for cigarette smoking behaviors, yet little is known on nicotine dependence (ND). Here, the authors perform a genome-wide association study on ND in 58,000 smokers, identifying five genome-wide significant loci.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Quach, Bryan C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bray, Michael J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gaddis, Nathan C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Liu, MengzhenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Palviainen, TeemuUNSPECIFIEDorcid.org/0000-0002-7847-8384UNSPECIFIED
Minica, Camelia C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zellers, StephanieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sherva, RichardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Aliev, FazilUNSPECIFIEDorcid.org/0000-0001-8357-4699UNSPECIFIED
Nothnagel, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Young, Kendra A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Marks, Jesse A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Young, HannahUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Carnes, Megan U.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Guo, YuelongUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Waldrop, AlexUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sey, Nancy Y. A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Landi, Maria T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
McNeil, Daniel W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Drichel, DmitriyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Farrer, Lindsay A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Markunas, Christina A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vink, Jacqueline M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hottenga, Jouke-JanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Iacono, William G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kranzler, Henry R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Saccone, Nancy L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Neale, Michael C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Madden, PamelaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rietschel, MarcellaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Marazita, Mary L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
McGue, MatthewUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Won, HyejungUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Winterer, GeorgUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Grucza, RichardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dick, Danielle M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gelernter, JoelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Caporaso, Neil E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Baker, Timothy B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Boomsma, Dorret I.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kaprio, JaakkoUNSPECIFIEDorcid.org/0000-0002-3716-2455UNSPECIFIED
Hokanson, John E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vrieze, ScottUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bierut, Laura J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Johnson, Eric O.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hancock, Dana B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-312253
DOI: 10.1038/s41467-020-19265-z
Journal or Publication Title: Nat. Commun.
Volume: 11
Number: 1
Date: 2020
Publisher: NATURE RESEARCH
Place of Publication: BERLIN
ISSN: 2041-1723
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
GENOME-WIDE ASSOCIATION; TOBACCO DEPENDENCE; LUNG-CANCER; FAGERSTROM TEST; WISCONSIN INVENTORY; SMOKING-CESSATION; VARIANTS; EXPRESSION; INSIGHTS; LOCIMultiple languages
Multidisciplinary SciencesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/31225

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