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; Dana B. Hancock

doi:10.1038/s41467-020-19265-z

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, Dana B. Hancock^*

^*Corresponding author for this work

RTI International
Washington University St. Louis
University of Minnesota Twin Cities
University of Helsinki
Vrije Universiteit Amsterdam
Boston University
Virginia Commonwealth University
Karabuk University
University of Cologne
University of Colorado Anschutz Medical Campus
GeneCentric Therapeutics, Inc.
University of North Carolina at Chapel Hill
National Institutes of Health
West Virginia University
Radboud University Nijmegen
University of Pennsylvania
VA Medical Center
Heidelberg University
University of Pittsburgh
Charité – Universitätsmedizin Berlin
Saint Louis University
Yale University
Department of Veterans Affairs
University of Wisconsin-Madison

Research output: Contribution to journal › Article › peer-review

90 Citations (Scopus)

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.

Original language	English
Article number	5562
Journal	Nature Communications
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41467-020-19265-z
Publication status	Published - 1 Dec 2020
Externally published	Yes

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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. Y. A., Landi, M. T., McNeil, D. W., ... Hancock, D. B. (2020). Expanding the genetic architecture of nicotine dependence and its shared genetics with multiple traits. Nature Communications, 11(1), Article 5562. https://doi.org/10.1038/s41467-020-19265-z

@article{39865b5fb682420cad8ca10b06badbf3,

title = "Expanding the genetic architecture of nicotine dependence and its shared genetics with multiple traits",

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 Fagerstr{\"o}m 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{\textendash}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.",

author = "Quach, \{Bryan C.\} and Bray, \{Michael J.\} and Gaddis, \{Nathan C.\} and Mengzhen Liu and Teemu Palviainen and Minica, \{Camelia C.\} and Stephanie Zellers and Richard Sherva and Fazil Aliev and Michael Nothnagel and Young, \{Kendra A.\} and Marks, \{Jesse A.\} and Hannah Young and Carnes, \{Megan U.\} and Yuelong Guo and Alex Waldrop and Sey, \{Nancy Y.A.\} and Landi, \{Maria T.\} and McNeil, \{Daniel W.\} and Dmitriy Drichel and Farrer, \{Lindsay A.\} and Markunas, \{Christina A.\} and Vink, \{Jacqueline M.\} and Hottenga, \{Jouke Jan\} and Iacono, \{William G.\} and Kranzler, \{Henry R.\} and Saccone, \{Nancy L.\} and Neale, \{Michael C.\} and Pamela Madden and Marcella Rietschel and Marazita, \{Mary L.\} and Matthew McGue and Hyejung Won and Georg Winterer and Richard Grucza and Dick, \{Danielle M.\} and Joel Gelernter and Caporaso, \{Neil E.\} and Baker, \{Timothy B.\} and Boomsma, \{Dorret I.\} and Jaakko Kaprio and Hokanson, \{John E.\} and Scott Vrieze and Bierut, \{Laura J.\} and Johnson, \{Eric O.\} and Hancock, \{Dana B.\}",

note = "Publisher Copyright: {\textcopyright} 2020, The Author(s).",

year = "2020",

month = dec,

day = "1",

doi = "10.1038/s41467-020-19265-z",

language = "English",

volume = "11",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Research",

number = "1",

}

Quach, BC, Bray, MJ, Gaddis, NC, Liu, M, Palviainen, T, Minica, CC, Zellers, S, Sherva, R, Aliev, F, Nothnagel, M, Young, KA, Marks, JA, Young, H, Carnes, MU, Guo, Y, Waldrop, A, Sey, NYA, Landi, MT, McNeil, DW, Drichel, D, Farrer, LA, Markunas, CA, Vink, JM, Hottenga, JJ, Iacono, WG, Kranzler, HR, Saccone, NL, Neale, MC, Madden, P, Rietschel, M, Marazita, ML, McGue, M, Won, H, Winterer, G, Grucza, R, Dick, DM, Gelernter, J, Caporaso, NE, Baker, TB, Boomsma, DI, Kaprio, J, Hokanson, JE, Vrieze, S, Bierut, LJ, Johnson, EO & Hancock, DB 2020, 'Expanding the genetic architecture of nicotine dependence and its shared genetics with multiple traits', Nature Communications, vol. 11, no. 1, 5562. https://doi.org/10.1038/s41467-020-19265-z

TY - JOUR

T1 - Expanding the genetic architecture of nicotine dependence and its shared genetics with multiple traits

AU - Quach, Bryan C.

AU - Bray, Michael J.

AU - Gaddis, Nathan C.

AU - Liu, Mengzhen

AU - Palviainen, Teemu

AU - Minica, Camelia C.

AU - Zellers, Stephanie

AU - Sherva, Richard

AU - Aliev, Fazil

AU - Nothnagel, Michael

AU - Young, Kendra A.

AU - Marks, Jesse A.

AU - Young, Hannah

AU - Carnes, Megan U.

AU - Guo, Yuelong

AU - Waldrop, Alex

AU - Sey, Nancy Y.A.

AU - Landi, Maria T.

AU - McNeil, Daniel W.

AU - Drichel, Dmitriy

AU - Farrer, Lindsay A.

AU - Markunas, Christina A.

AU - Vink, Jacqueline M.

AU - Hottenga, Jouke Jan

AU - Iacono, William G.

AU - Kranzler, Henry R.

AU - Saccone, Nancy L.

AU - Neale, Michael C.

AU - Madden, Pamela

AU - Rietschel, Marcella

AU - Marazita, Mary L.

AU - McGue, Matthew

AU - Won, Hyejung

AU - Winterer, Georg

AU - Grucza, Richard

AU - Dick, Danielle M.

AU - Gelernter, Joel

AU - Caporaso, Neil E.

AU - Baker, Timothy B.

AU - Boomsma, Dorret I.

AU - Kaprio, Jaakko

AU - Hokanson, John E.

AU - Vrieze, Scott

AU - Bierut, Laura J.

AU - Johnson, Eric O.

AU - Hancock, Dana B.

PY - 2020/12/1

Y1 - 2020/12/1

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85094919852

U2 - 10.1038/s41467-020-19265-z

DO - 10.1038/s41467-020-19265-z

M3 - Article

C2 - 33144568

AN - SCOPUS:85094919852

SN - 2041-1723

VL - 11

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 5562

ER -

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

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