Genome-Wide Meta-Analyses of FTND and TTFC Phenotypes-Reference-Cited by-同舟云学术

Genome-Wide Meta-Analyses of FTND and TTFC Phenotypes

Published:2019-07-11 Issue:6 Volume:22 Page:900-909
ISSN:1469-994X
Container-title:Nicotine & Tobacco Research
language:en
Short-container-title:

Author:

Chen Jingchun¹,Loukola Anu²³,Gillespie Nathan A⁴,Peterson Roseann⁴,Jia Peilin⁵,Riley Brien⁴,Maes Hermine⁴,Dick Daniella M⁶,Kendler Kenneth S⁴,Damaj M Imad⁷,Miles Michael F⁷,Zhao Zhongming⁵,Li Ming D⁸,Vink Jacqueline M⁹¹⁰,Minica Camelia C⁹¹¹¹²,Willemsen Gonneke⁹¹¹¹²,Boomsma Dorret I⁹¹¹¹²,Qaiser Beenish²³,Madden Pamela A F¹³,Korhonen Tellervo²¹⁴,Jousilahti Pekka¹⁵,Hällfors Jenni³,Gelernter Joel¹⁶,Kranzler Henry R¹⁷,Sherva Richard¹⁸,Farrer Lindsay¹⁸,Maher Brion¹⁹,Vanyukov Michael²⁰,Taylor Michelle²¹,Ware Jenifer J²¹,Munafò Marcus R²¹,Lutz Sharon M²²,Hokanson John E²²,Gu Fangyi²³,Landi Maria T²³,Caporaso Neil E²³,Hancock Dana B²⁴,Gaddis Nathan C²⁵,Baker Timothy B²⁶,Bierut Laura J¹³,Johnson Eric O²⁴²⁷,Chenoweth Meghan²⁸,Lerman Caryn²⁹,Tyndale Rachel²⁸,Kaprio Jaakko²³,Chen Xiangning¹⁴³⁰

Affiliation:

1. Nevada Institute of Personalized Medicine, University of Nevada Las Vegas, Las Vegas, NV

2. Department of Public Health, University of Helsinki, Helsinki, FI, Finland

3. Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland

4. Virginia Institute of Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA

5. School of Biomedical Informatics, University of Texas Health Science Center at Houston, Houston, TX

6. Department of Psychology, Virginia Commonwealth University, Richmond, VA

7. Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA

8. 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

9. Netherlands Twin Register, Department of Biological Psychology, VU University, the Netherlands

10. Behavioural Science Institute, Radboud University, Nijmegen, the Netherlands

11. Neuroscience Campus Amsterdam, the Netherlands

12. EMGO+ Institute for Health and Care Research, VU Medical Center, Amsterdam, the Netherlands

13. Department of Psychiatry, Washington University, St. Louis, MO

14. Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Finland

15. National Institute for Health and Welfare, Helsinki, Finland

16. Department of Psychiatry, Yale University, New Haven, CT

17. Department of Psychiatry, University of Pennsylvania, Philadelphia, PA

18. Section of Biomedical Genetics, Department of Medicine, Boston University School of Medicine, Boston, MA

19. Department of Mental Health, Johns Hopkins University, Baltimore, MD

20. Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA

21. MRC Integrative Epidemiology Unit (IEU) at the University of Bristol, Bristol, BS, UK

22. Department of Biostatistics and Informatics, University of Colorado Anschutz Medical Campus, Aurora, CO

23. 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

24. Behavioral Health and Criminal Justice Division, RTI International, Research Triangle Park, NC

25. Research Computing Division, RTI International, Research Triangle Park, NC

26. Center for Tobacco Research and Intervention, University of Wisconsin, Madison, WI

27. Fellow Program, RTI International, Research Triangle Park, NC

28. Centre for Addiction and Mental Health, and Departments of Pharmacology and Toxicology, and Psychiatry, University of Toronto, Toronto, Canada

29. Center for Interdisciplinary Research on Nicotine Addiction, Department of Psychiatry, University of Pennsylvania, Philadelphia, PA

30. Department of Psychology, University of Nevada Las Vegas, Las Vegas, NV

Abstract

Abstract 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.

Funder

National Institutes of Health

Publisher

Oxford University Press (OUP)

Subject

Public Health, Environmental and Occupational Health

Link

http://academic.oup.com/ntr/advance-article-pdf/doi/10.1093/ntr/ntz099/28927391/ntz099.pdf

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