Genome-Wide Meta-Analyses of FTND and TTFC Phenotypes

2019, Nicotine & Tobacco Research

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...

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. (2019). Genome-Wide Meta-Analyses of FTND and TTFC Phenotypes. Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco, [ntz099]. https://doi.org/10.1093/ntr/ntz099 Peer reviewed version Link to published version (if available): 10.1093/ntr/ntz099 Link to publication record in Explore Bristol Research PDF-document This is the author accepted manuscript (AAM). The final published version (version of record) is available online via Oxford University Press at https://doi.org/10.1093/ntr/ntz099 . Please refer to any applicable terms of use of the publisher. University of Bristol - Explore Bristol Research General rights This document is made available in accordance with publisher policies. Please cite only the published version using the reference above. Full terms of use are available: http://www.bristol.ac.uk/red/research-policy/pure/user-guides/ebr-terms/ Supplementary Figures Figure S1.A. Manhattan plot of the FTND meta-analysis. The red line represents the genome-wide significance threshold (P < 5×10-8), while the blue line represents suggestive association threshold (P < 5×10-5). Figure S1.B. QQ plot of the FTND meta-analysis. Figure S1.C. Manhattan plot of the TTFC meta-analysis. The red line represents the genome-wide significance threshold (P<5×10-8), while the blue line represents suggestive association threshold (P < 5×10-5). Figure S1.D. QQ plot of the TTFC meta-analysis. Figure S2. Chromosomal regions with markers reaching genome-wide significance in FTND and TTFC meta-analyses. A. CHRNA5-CHRNA3-CHRNB4 region on chromosome 15 for FTND; B. CHRNA5-CHRNA3CHRNB4 region on chromosome 15 for TTFC; C. AA333164 region on chromosome 14 for TTFC; D. SORB2 region on chromosome 4 for TTFC; E. BG182718 region on chromosome 14 for TTFC.

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Genome-Wide Meta-Analyses of FTND and TTFC Phenotypes

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