Genome-Wide Meta-Analyses of FTND and TTFC Phenotypes

Jingchun Chen; Anu Loukola; Nathan A. Gillespie; Roseann Peterson; Peilin Jia; Brien Riley; Hermine Maes; Daniella M. Dick; Kenneth S. Kendler; M. Imad Damaj; Michael F. Miles; Zhongming Zhao; Ming D. Li; Jacqueline M. Vink; Camelia C. Minica; Gonneke Willemsen; Dorret I. Boomsma; Beenish Qaiser; Pamela A.F. Madden; Tellervo Korhonen; Pekka Jousilahti; Jenni Hällfors; Joel Gelernter; Henry R. Kranzler; Richard Sherva; Lindsay Farrer; Brion Maher; Michael Vanyukov; Michelle Taylor; Jenifer J. Ware; Marcus R. Munafò; Sharon M. Lutz; John E. Hokanson; Fangyi Gu; Maria T. Landi; Neil E. Caporaso; Dana B. Hancock; Nathan C. Gaddis; Timothy B. Baker; Laura J. Bierut; Eric O. Johnson; Meghan Chenoweth; Caryn Lerman; Rachel Tyndale; Jaakko Kaprio; Xiangning Chen

doi:10.1093/ntr/ntz099

Genome-Wide Meta-Analyses of FTND and TTFC Phenotypes

Jingchun Chen, Anu Loukola, Nathan A. Gillespie, Roseann Peterson, Peilin Jia, Brien Riley, Hermine Maes, Daniella M. Dick, Kenneth S. Kendler, M. Imad Damaj, Michael F. Miles, Zhongming Zhao, Ming D. Li, Jacqueline M. Vink, Camelia C. Minica, Gonneke Willemsen, Dorret I. Boomsma, Beenish Qaiser, Pamela A.F. Madden, Tellervo KorhonenPekka Jousilahti, Jenni Hällfors, Joel Gelernter, Henry R. Kranzler, Richard Sherva, Lindsay Farrer, Brion Maher, Michael Vanyukov, Michelle Taylor, Jenifer J. Ware, Marcus R. Munafò, Sharon M. Lutz, John E. Hokanson, Fangyi Gu, Maria T. Landi, Neil E. Caporaso, Dana B. Hancock, Nathan C. Gaddis, Timothy B. Baker, Laura J. Bierut, Eric O. Johnson, Meghan Chenoweth, Caryn Lerman, Rachel Tyndale, Jaakko Kaprio, Xiangning Chen

Bloomberg School of Public Health

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

1 Scopus citations

Abstract

Introduction: FTND (Fagerström test for nicotine dependence) and TTFC (time to smoke first cigarette in the morning) are common measures of nicotine dependence (ND). However, genome-wide meta-analysis for these phenotypes has not been reported. Methods: Genome-wide meta-analyses for FTND (N = 19,431) and TTFC (N = 18,567) phenotypes were conducted for adult smokers of European ancestry from 14 independent cohorts. Results: We found that SORBS2 on 4q35 (p = 4.05 × 10-8), BG182718 on 11q22 (p = 1.02 × 10-8), and AA333164 on 14q21 (p = 4.11 × 10-9) were associated with TTFC phenotype. We attempted replication of leading candidates with independent samples (FTND, N = 7010 and TTFC, N = 10 061), however, due to limited power of the replication samples, the replication of these new loci did not reach significance. In gene-based analyses, COPB2 was found associated with FTND phenotype, and TFCP2L1, RELN, and INO80C were associated with TTFC phenotype. In pathway and network analyses, we found that the interconnected interactions among the endocytosis, regulation of actin cytoskeleton, axon guidance, MAPK signaling, and chemokine signaling pathways were involved in ND. Conclusions: Our analyses identified several promising candidates for both FTND and TTFC phenotypes, and further verification of these candidates was necessary. Candidates supported by both FTND and TTFC (CHRNA4, THSD7B, RBFOX1, and ZNF804A) were associated with addiction to alcohol, cocaine, and heroin, and were associated with autism and schizophrenia. We also identified novel pathways involved in cigarette smoking. The pathway interactions highlighted the importance of receptor recycling and internalization in ND. Implications: Understanding the genetic architecture of cigarette smoking and ND is critical to develop effective prevention and treatment. Our study identified novel candidates and biological pathways involved in FTND and TTFC phenotypes, and this will facilitate further investigation of these candidates and pathways.

Original language	English (US)
Pages (from-to)	900-909
Number of pages	10
Journal	Nicotine and Tobacco Research
Volume	22
Issue number	6
DOIs	https://doi.org/10.1093/ntr/ntz099
State	Published - Jun 1 2020

ASJC Scopus subject areas

General Medicine

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10.1093/ntr/ntz099

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Chen, J., Loukola, A., Gillespie, N. A., Peterson, R., Jia, P., Riley, B., Maes, H., Dick, D. M., Kendler, K. S., Damaj, M. I., Miles, M. F., Zhao, Z., Li, M. D., Vink, J. M., Minica, C. C., Willemsen, G., Boomsma, D. I., Qaiser, B., Madden, P. A. F., ... Chen, X. (2020). Genome-Wide Meta-Analyses of FTND and TTFC Phenotypes. Nicotine and Tobacco Research, 22(6), 900-909. https://doi.org/10.1093/ntr/ntz099

Chen, J, Loukola, A, Gillespie, NA, Peterson, R, Jia, P, Riley, B, Maes, H, Dick, DM, Kendler, KS, Damaj, MI, Miles, MF, Zhao, Z, Li, MD, Vink, JM, Minica, CC, Willemsen, G, Boomsma, DI, Qaiser, B, Madden, PAF, Korhonen, T, Jousilahti, P, Hällfors, J, Gelernter, J, Kranzler, HR, Sherva, R, Farrer, L, Maher, B, Vanyukov, M, Taylor, M, Ware, JJ, Munafò, MR, Lutz, SM, Hokanson, JE, Gu, F, Landi, MT, Caporaso, NE, Hancock, DB, Gaddis, NC, Baker, TB, Bierut, LJ, Johnson, EO, Chenoweth, M, Lerman, C, Tyndale, R, Kaprio, J & Chen, X 2020, 'Genome-Wide Meta-Analyses of FTND and TTFC Phenotypes', Nicotine and Tobacco Research, vol. 22, no. 6, pp. 900-909. https://doi.org/10.1093/ntr/ntz099

@article{3abdc4e1e42f407196c117f3f1f17722,

title = "Genome-Wide Meta-Analyses of FTND and TTFC Phenotypes",

abstract = "Introduction: FTND (Fagerstr{\"o}m test for nicotine dependence) and TTFC (time to smoke first cigarette in the morning) are common measures of nicotine dependence (ND). However, genome-wide meta-analysis for these phenotypes has not been reported. Methods: Genome-wide meta-analyses for FTND (N = 19,431) and TTFC (N = 18,567) phenotypes were conducted for adult smokers of European ancestry from 14 independent cohorts. Results: We found that SORBS2 on 4q35 (p = 4.05 × 10-8), BG182718 on 11q22 (p = 1.02 × 10-8), and AA333164 on 14q21 (p = 4.11 × 10-9) were associated with TTFC phenotype. We attempted replication of leading candidates with independent samples (FTND, N = 7010 and TTFC, N = 10 061), however, due to limited power of the replication samples, the replication of these new loci did not reach significance. In gene-based analyses, COPB2 was found associated with FTND phenotype, and TFCP2L1, RELN, and INO80C were associated with TTFC phenotype. In pathway and network analyses, we found that the interconnected interactions among the endocytosis, regulation of actin cytoskeleton, axon guidance, MAPK signaling, and chemokine signaling pathways were involved in ND. Conclusions: Our analyses identified several promising candidates for both FTND and TTFC phenotypes, and further verification of these candidates was necessary. Candidates supported by both FTND and TTFC (CHRNA4, THSD7B, RBFOX1, and ZNF804A) were associated with addiction to alcohol, cocaine, and heroin, and were associated with autism and schizophrenia. We also identified novel pathways involved in cigarette smoking. The pathway interactions highlighted the importance of receptor recycling and internalization in ND. Implications: Understanding the genetic architecture of cigarette smoking and ND is critical to develop effective prevention and treatment. Our study identified novel candidates and biological pathways involved in FTND and TTFC phenotypes, and this will facilitate further investigation of these candidates and pathways.",

author = "Jingchun Chen and Anu Loukola and Gillespie, {Nathan A.} and Roseann Peterson and Peilin Jia and Brien Riley and Hermine Maes and Dick, {Daniella M.} and Kendler, {Kenneth S.} and Damaj, {M. Imad} and Miles, {Michael F.} and Zhongming Zhao and Li, {Ming D.} and Vink, {Jacqueline M.} and Minica, {Camelia C.} and Gonneke Willemsen and Boomsma, {Dorret I.} and Beenish Qaiser and Madden, {Pamela A.F.} and Tellervo Korhonen and Pekka Jousilahti and Jenni H{\"a}llfors and Joel Gelernter and Kranzler, {Henry R.} and Richard Sherva and Lindsay Farrer and Brion Maher and Michael Vanyukov and Michelle Taylor and Ware, {Jenifer J.} and Munaf{\`o}, {Marcus R.} and Lutz, {Sharon M.} and Hokanson, {John E.} and Fangyi Gu and Landi, {Maria T.} and Caporaso, {Neil E.} and Hancock, {Dana B.} and Gaddis, {Nathan C.} and Baker, {Timothy B.} and Bierut, {Laura J.} and Johnson, {Eric O.} and Meghan Chenoweth and Caryn Lerman and Rachel Tyndale and Jaakko Kaprio and Xiangning Chen",

note = "Publisher Copyright: {\textcopyright} 2019 The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved.For permissions, please e-mail: journals.permissions@oup.com.",

year = "2020",

month = jun,

day = "1",

doi = "10.1093/ntr/ntz099",

language = "English (US)",

volume = "22",

pages = "900--909",

journal = "Nicotine and Tobacco Research",

issn = "1462-2203",

publisher = "Oxford University Press",

number = "6",

}

TY - JOUR

T1 - Genome-Wide Meta-Analyses of FTND and TTFC Phenotypes

AU - Chen, Jingchun

AU - Loukola, Anu

AU - Gillespie, Nathan A.

AU - Peterson, Roseann

AU - Jia, Peilin

AU - Riley, Brien

AU - Maes, Hermine

AU - Dick, Daniella M.

AU - Kendler, Kenneth S.

AU - Damaj, M. Imad

AU - Miles, Michael F.

AU - Zhao, Zhongming

AU - Li, Ming D.

AU - Vink, Jacqueline M.

AU - Minica, Camelia C.

AU - Willemsen, Gonneke

AU - Boomsma, Dorret I.

AU - Qaiser, Beenish

AU - Madden, Pamela A.F.

AU - Korhonen, Tellervo

AU - Jousilahti, Pekka

AU - Hällfors, Jenni

AU - Gelernter, Joel

AU - Kranzler, Henry R.

AU - Sherva, Richard

AU - Farrer, Lindsay

AU - Maher, Brion

AU - Vanyukov, Michael

AU - Taylor, Michelle

AU - Ware, Jenifer J.

AU - Munafò, Marcus R.

AU - Lutz, Sharon M.

AU - Hokanson, John E.

AU - Gu, Fangyi

AU - Landi, Maria T.

AU - Caporaso, Neil E.

AU - Hancock, Dana B.

AU - Gaddis, Nathan C.

AU - Baker, Timothy B.

AU - Bierut, Laura J.

AU - Johnson, Eric O.

AU - Chenoweth, Meghan

AU - Lerman, Caryn

AU - Tyndale, Rachel

AU - Kaprio, Jaakko

AU - Chen, Xiangning

N1 - Publisher Copyright: © 2019 The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved.For permissions, please e-mail: journals.permissions@oup.com.

PY - 2020/6/1

Y1 - 2020/6/1

N2 - Introduction: FTND (Fagerström test for nicotine dependence) and TTFC (time to smoke first cigarette in the morning) are common measures of nicotine dependence (ND). However, genome-wide meta-analysis for these phenotypes has not been reported. Methods: Genome-wide meta-analyses for FTND (N = 19,431) and TTFC (N = 18,567) phenotypes were conducted for adult smokers of European ancestry from 14 independent cohorts. Results: We found that SORBS2 on 4q35 (p = 4.05 × 10-8), BG182718 on 11q22 (p = 1.02 × 10-8), and AA333164 on 14q21 (p = 4.11 × 10-9) were associated with TTFC phenotype. We attempted replication of leading candidates with independent samples (FTND, N = 7010 and TTFC, N = 10 061), however, due to limited power of the replication samples, the replication of these new loci did not reach significance. In gene-based analyses, COPB2 was found associated with FTND phenotype, and TFCP2L1, RELN, and INO80C were associated with TTFC phenotype. In pathway and network analyses, we found that the interconnected interactions among the endocytosis, regulation of actin cytoskeleton, axon guidance, MAPK signaling, and chemokine signaling pathways were involved in ND. Conclusions: Our analyses identified several promising candidates for both FTND and TTFC phenotypes, and further verification of these candidates was necessary. Candidates supported by both FTND and TTFC (CHRNA4, THSD7B, RBFOX1, and ZNF804A) were associated with addiction to alcohol, cocaine, and heroin, and were associated with autism and schizophrenia. We also identified novel pathways involved in cigarette smoking. The pathway interactions highlighted the importance of receptor recycling and internalization in ND. Implications: Understanding the genetic architecture of cigarette smoking and ND is critical to develop effective prevention and treatment. Our study identified novel candidates and biological pathways involved in FTND and TTFC phenotypes, and this will facilitate further investigation of these candidates and pathways.

AB - Introduction: FTND (Fagerström test for nicotine dependence) and TTFC (time to smoke first cigarette in the morning) are common measures of nicotine dependence (ND). However, genome-wide meta-analysis for these phenotypes has not been reported. Methods: Genome-wide meta-analyses for FTND (N = 19,431) and TTFC (N = 18,567) phenotypes were conducted for adult smokers of European ancestry from 14 independent cohorts. Results: We found that SORBS2 on 4q35 (p = 4.05 × 10-8), BG182718 on 11q22 (p = 1.02 × 10-8), and AA333164 on 14q21 (p = 4.11 × 10-9) were associated with TTFC phenotype. We attempted replication of leading candidates with independent samples (FTND, N = 7010 and TTFC, N = 10 061), however, due to limited power of the replication samples, the replication of these new loci did not reach significance. In gene-based analyses, COPB2 was found associated with FTND phenotype, and TFCP2L1, RELN, and INO80C were associated with TTFC phenotype. In pathway and network analyses, we found that the interconnected interactions among the endocytosis, regulation of actin cytoskeleton, axon guidance, MAPK signaling, and chemokine signaling pathways were involved in ND. Conclusions: Our analyses identified several promising candidates for both FTND and TTFC phenotypes, and further verification of these candidates was necessary. Candidates supported by both FTND and TTFC (CHRNA4, THSD7B, RBFOX1, and ZNF804A) were associated with addiction to alcohol, cocaine, and heroin, and were associated with autism and schizophrenia. We also identified novel pathways involved in cigarette smoking. The pathway interactions highlighted the importance of receptor recycling and internalization in ND. Implications: Understanding the genetic architecture of cigarette smoking and ND is critical to develop effective prevention and treatment. Our study identified novel candidates and biological pathways involved in FTND and TTFC phenotypes, and this will facilitate further investigation of these candidates and pathways.

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JO - Nicotine and Tobacco Research

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Genome-Wide Meta-Analyses of FTND and TTFC Phenotypes

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