Response to Kaufman and Harper Letter
Publication: American Journal of Psychiatry
To the Editor: A great deal of research shows that the CHRNA5-CHRNA3-CHRNB4 haplotypes are associated with measures of smoking quantity (1–4). However, earlier research presented inconsistent results with regard to the association of these haplotypes with smoking cessation likelihood. Our findings show that these haplotypes can predict cessation success and also that their association with cessation likelihood differs depending on the use of smoking cessation pharmacotherapy in the quit attempt. In essence, we obtained a significant interaction effect between haplotype and treatment condition such that individuals with haplotypes that confer a heightened risk of relapse benefited much more from cessation pharmacotherapy than did individuals without such haplotypes.
In our study, we used both the Cox proportional hazards model to estimate the likelihood of smoking relapse over time and the logistic regression model to estimate the odds of smoking abstinence, and both showed greater benefit from pharmacotherapy in individuals with risk haplotypes than in those without such haplotypes. However, at one point in the article, we discussed the odds ratio generated by the logistic regression as if it reflected relative risk. In their letter, Kaufman and Harper note that the odds ratio and the relative risk ratio diverge for analyses of common events.
We agree with Kaufman and Harper’s observation and appreciate their pointing out that the results of our research appear even more striking when portrayed in terms of number needed to treat. In our study, the number needed to treat is seven when computed across all individuals regardless of their haplotype status, supporting the established effect of pharmacotherapy. However, this number varies widely depending on the individual’s haplotype. Based on their absolute risks, the number needed to treat is four for smokers with the high-risk haplotype, seven for smokers with the intermediate-risk haplotype, and >1,000 for smokers with the low-risk haplotype. We agree with Kaufman and Harper that a number needed to treat of four is an impressive finding compared with the numbers needed to treat of many existing pharmacotherapies. The wide variation between smokers with different haplotypes supports the notion that personalized smoking cessation intervention based on genotype could meaningfully increase the efficiency of such treatment.
References
1.
Liu JZ, Tozzi F, Waterworth DM, Pillai SG, Muglia P, Middleton L, Berrettini W, Knouff CW, Yuan X, Waeber G, Vollenweider P, Preisig M, Wareham NJ, Zhao JH, Loos RJ, Barroso I, Khaw KT, Grundy S, Barter P, Mahley R, Kesaniemi A, McPherson R, Vincent JB, Strauss J, Kennedy JL, Farmer A, McGuffin P, Day R, Matthews K, Bakke P, Gulsvik A, Lucae S, Ising M, Brueckl T, Horstmann S, Wichmann HE, Rawal R, Dahmen N, Lamina C, Polasek O, Zgaga L, Huffman J, Campbell S, Kooner J, Chambers JC, Burnett MS, Devaney JM, Pichard AD, Kent KM, Satler L, Lindsay JM, Waksman R, Epstein S, Wilson JF, Wild SH, Campbell H, Vitart V, Reilly MP, Li M, Qu L, Wilensky R, Matthai W, Hakonarson HH, Rader DJ, Franke A, Wittig M, Schäfer A, Uda M, Terracciano A, Xiao X, Busonero F, Scheet P, Schlessinger D, St Clair D, Rujescu D, Abecasis GR, Grabe HJ, Teumer A, Völzke H, Petersmann A, John U, Rudan I, Hayward C, Wright AF, Kolcic I, Wright BJ, Thompson JR, Balmforth AJ, Hall AS, Samani NJ, Anderson CA, Ahmad T, Mathew CG, Parkes M, Satsangi J, Caulfield M, Munroe PB, Farrall M, Dominiczak A, Worthington J, Thomson W, Eyre S, Barton A, Mooser V, Francks C, Marchini JWellcome Trust Case Control Consortium: Meta-analysis and imputation refines the association of 15q25 with smoking quantity. Nat Genet 2010; 42:436–440
2.
Saccone NL, Culverhouse RC, Schwantes-An TH, Cannon DS, Chen X, Cichon S, Giegling I, Han S, Han Y, Keskitalo-Vuokko K, Kong X, Landi MT, Ma JZ, Short SE, Stephens SH, Stevens VL, Sun L, Wang Y, Wenzlaff AS, Aggen SH, Breslau N, Broderick P, Chatterjee N, Chen J, Heath AC, Heliövaara M, Hoft NR, Hunter DJ, Jensen MK, Martin NG, Montgomery GW, Niu T, Payne TJ, Peltonen L, Pergadia ML, Rice JP, Sherva R, Spitz MR, Sun J, Wang JC, Weiss RB, Wheeler W, Witt SH, Yang BZ, Caporaso NE, Ehringer MA, Eisen T, Gapstur SM, Gelernter J, Houlston R, Kaprio J, Kendler KS, Kraft P, Leppert MF, Li MD, Madden PA, Nöthen MM, Pillai S, Rietschel M, Rujescu D, Schwartz A, Amos CI, Bierut LJ: Multiple independent loci at chromosome 15q25.1 affect smoking quantity: a meta-analysis and comparison with lung cancer and COPD. PLoS Genet 2010; 6:e1001053
3.
Tobacco and Genetics Consortium: Genome-wide meta-analyses identify multiple loci associated with smoking behavior. Nat Genet 2010; 42:441–447
4.
Thorgeirsson TE, Gudbjartsson DF, Surakka I, Vink JM, Amin N, Geller F, Sulem P, Rafnar T, Esko T, Walter S, Gieger C, Rawal R, Mangino M, Prokopenko I, Mägi R, Keskitalo K, Gudjonsdottir IH, Gretarsdottir S, Stefansson H, Thompson JR, Aulchenko YS, Nelis M, Aben KK, den Heijer M, Dirksen A, Ashraf H, Soranzo N, Valdes AM, Steves C, Uitterlinden AG, Hofman A, Tönjes A, Kovacs P, Hottenga JJ, Willemsen G, Vogelzangs N, Döring A, Dahmen N, Nitz B, Pergadia ML, Saez B, De Diego V, Lezcano V, Garcia-Prats MD, Ripatti S, Perola M, Kettunen J, Hartikainen AL, Pouta A, Laitinen J, Isohanni M, Huei-Yi S, Allen M, Krestyaninova M, Hall AS, Jones GT, van Rij AM, Mueller T, Dieplinger B, Haltmayer M, Jonsson S, Matthiasson SE, Oskarsson H, Tyrfingsson T, Kiemeney LA, Mayordomo JI, Lindholt JS, Pedersen JH, Franklin WA, Wolf H, Montgomery GW, Heath AC, Martin NG, Madden PA, Giegling I, Rujescu D, Järvelin MR, Salomaa V, Stumvoll M, Spector TD, Wichmann HE, Metspalu A, Samani NJ, Penninx BW, Oostra BA, Boomsma DI, Tiemeier H, van Duijn CM, Kaprio J, Gulcher JR, McCarthy MI, Peltonen L, Thorsteinsdottir U, Stefansson KENGAGE Consortium: Sequence variants at CHRNB3-CHRNA6 and CYP2A6 affect smoking behavior. Nat Genet 2010; 42:448–453
Information & Authors
Information
Published In
History
Accepted: July 2012
Published online: 1 October 2012
Published in print: October 2012
Authors
Competing Interests
The authors’ disclosures accompany the original article.
Metrics & Citations
Metrics
Citations
Export Citations
If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download.
For more information or tips please see 'Downloading to a citation manager' in the Help menu.
View Options
View options
PDF/EPUB
View PDF/EPUBGet Access
Login options
Already a subscriber? Access your subscription through your login credentials or your institution for full access to this article.
Personal login Institutional Login Open Athens loginNot a subscriber?
PsychiatryOnline subscription options offer access to the DSM-5-TR® library, books, journals, CME, and patient resources. This all-in-one virtual library provides psychiatrists and mental health professionals with key resources for diagnosis, treatment, research, and professional development.
Need more help? PsychiatryOnline Customer Service may be reached by emailing [email protected] or by calling 800-368-5777 (in the U.S.) or 703-907-7322 (outside the U.S.).