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

Autor:	Chen J; Nevada Institute of Personalized Medicine, University of Nevada Las Vegas, Las Vegas, NV., Loukola A; Department of Public Health, University of Helsinki, Helsinki, FI, Finland.; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland., Gillespie NA; Virginia Institute of Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA., Peterson R; Virginia Institute of Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA., Jia P; School of Biomedical Informatics, University of Texas Health Science Center at Houston, Houston, TX., Riley B; Virginia Institute of Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA., Maes H; Virginia Institute of Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA., Dick DM; Department of Psychology, Virginia Commonwealth University, Richmond, VA., Kendler KS; Virginia Institute of Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA., Damaj MI; Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA., Miles MF; Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA., Zhao Z; School of Biomedical Informatics, University of Texas Health Science Center at Houston, Houston, TX., Li MD; State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China., Vink JM; Netherlands Twin Register, Department of Biological Psychology, VU University, the Netherlands.; Behavioural Science Institute, Radboud University, Nijmegen, the Netherlands., Minica CC; Netherlands Twin Register, Department of Biological Psychology, VU University, the Netherlands.; Neuroscience Campus Amsterdam, the Netherlands.; EMGO+ Institute for Health and Care Research, VU Medical Center, Amsterdam, the Netherlands., Willemsen G; Netherlands Twin Register, Department of Biological Psychology, VU University, the Netherlands.; Neuroscience Campus Amsterdam, the Netherlands.; EMGO+ Institute for Health and Care Research, VU Medical Center, Amsterdam, the Netherlands., Boomsma DI; Netherlands Twin Register, Department of Biological Psychology, VU University, the Netherlands.; Neuroscience Campus Amsterdam, the Netherlands.; EMGO+ Institute for Health and Care Research, VU Medical Center, Amsterdam, the Netherlands., Qaiser B; Department of Public Health, University of Helsinki, Helsinki, FI, Finland.; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland., Madden PAF; Department of Psychiatry, Washington University, St. Louis, MO., Korhonen T; Department of Public Health, University of Helsinki, Helsinki, FI, Finland.; Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Finland., Jousilahti P; National Institute for Health and Welfare, Helsinki, Finland., Hällfors J; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland., Gelernter J; Department of Psychiatry, Yale University, New Haven, CT., Kranzler HR; Department of Psychiatry, University of Pennsylvania, Philadelphia, PA., Sherva R; Section of Biomedical Genetics, Department of Medicine, Boston University School of Medicine, Boston, MA., Farrer L; Section of Biomedical Genetics, Department of Medicine, Boston University School of Medicine, Boston, MA., Maher B; Department of Mental Health, Johns Hopkins University, Baltimore, MD., Vanyukov M; Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA., Taylor M; MRC Integrative Epidemiology Unit (IEU) at the University of Bristol, Bristol, BS, UK., Ware JJ; MRC Integrative Epidemiology Unit (IEU) at the University of Bristol, Bristol, BS, UK., Munafò MR; MRC Integrative Epidemiology Unit (IEU) at the University of Bristol, Bristol, BS, UK., Lutz SM; Department of Biostatistics and Informatics, University of Colorado Anschutz Medical Campus, Aurora, CO., Hokanson JE; Department of Biostatistics and Informatics, University of Colorado Anschutz Medical Campus, Aurora, CO., Gu F; Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, United States Department of Health and Human Services, Bethesda, MD., Landi MT; Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, United States Department of Health and Human Services, Bethesda, MD., Caporaso NE; Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, United States Department of Health and Human Services, Bethesda, MD., Hancock DB; Behavioral Health and Criminal Justice Division, RTI International, Research Triangle Park, NC., Gaddis NC; Research Computing Division, RTI International, Research Triangle Park, NC., Baker TB; Center for Tobacco Research and Intervention, University of Wisconsin, Madison, WI., Bierut LJ; Department of Psychiatry, Washington University, St. Louis, MO., Johnson EO; Behavioral Health and Criminal Justice Division, RTI International, Research Triangle Park, NC.; Fellow Program, RTI International, Research Triangle Park, NC., Chenoweth M; Centre for Addiction and Mental Health, and Departments of Pharmacology and Toxicology, and Psychiatry, University of Toronto, Toronto, Canada., Lerman C; Center for Interdisciplinary Research on Nicotine Addiction, Department of Psychiatry, University of Pennsylvania, Philadelphia, PA., Tyndale R; Centre for Addiction and Mental Health, and Departments of Pharmacology and Toxicology, and Psychiatry, University of Toronto, Toronto, Canada., Kaprio J; Department of Public Health, University of Helsinki, Helsinki, FI, Finland.; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland., Chen X; Nevada Institute of Personalized Medicine, University of Nevada Las Vegas, Las Vegas, NV.; Virginia Institute of Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA.; Department of Psychology, University of Nevada Las Vegas, Las Vegas, NV.
Jazyk:	angličtina
Zdroj:	Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco [Nicotine Tob Res] 2020 May 26; Vol. 22 (6), pp. 900-909.
DOI:	10.1093/ntr/ntz099
Abstrakt:	Introduction: FTND (Fagerstrӧm 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. (© 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.)
Databáze:	MEDLINE
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