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Smoking quit success genotype score predicts quit success and distinct patterns of developmental involvement with common addictive substances

Molecular Psychiatry volume 19, pages 50–54 (2014)Cite this article

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Abstract

Genotype scores that predict relevant clinical outcomes may detect other disease features and help direct prevention efforts. We report data that validate a previously established v1.0 smoking cessation quit success genotype score and describe striking differences in the score in individuals who display differing developmental trajectories of use of common addictive substances. In a cessation study, v1.0 genotype scores predicted ability to quit with P=0.00056 and area under receiver-operating characteristic curve 0.66. About 43% vs 13% quit in the upper vs lower genotype score terciles. Latent class growth analyses of a developmentally assessed sample identified three latent classes based on substance use. Higher v1.0 scores were associated with (a) higher probabilities of participant membership in a latent class that displayed low use of common addictive substances during adolescence (P=0.0004) and (b) lower probabilities of membership in a class that reported escalating use (P=0.001). These results indicate that: (a) we have identified genetic predictors of smoking cessation success, (b) genetic influences on quit success overlap with those that influence the rate at which addictive substance use is taken up during adolescence and (c) individuals at genetic risk for both escalating use of addictive substances and poor abilities to quit may provide especially urgent focus for prevention efforts.

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Acknowledgements

This study was supported by the National Institutes of Health (NIH)–Intramural Research Program, National Institute on Drug Abuse, Department of Health and Human Services (Dr Uhl); a grant to Duke University (PI, Dr Rose) from Philip Morris, USA for the work performed before January 2012; NIDA grants R01-DA009897 (WE) and 4R37DA011796-11 (NI). The funders had no role in the planning or execution of the study, data analysis or publication of results. We are grateful to TGEN investigators for generous access to Alzheimer’s disease GWAS genotype data and D Sisto for its analysis, to E Westman for assistance with the smoking cessation clinical trial, for each of the prevention study investigators, especially S Kellam, for the sustained cooperation of the study participants and for help and thoughtful advice from C Johnson, J Schroder, P Zandi and K Masyn. The underlying smoking cessation clinical trial was registered with clinicaltrials.gov (NCT00894166).

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Authors and Affiliations

  1. Molecular Neurobiology Branch, NIH-IRP, NIDA, Baltimore, MD, USA

    G R Uhl, D Walther & C Fisher

  2. Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA

    R Musci, W W Eaton & N Ialongo

  3. Department of Epidemiology, Michigan State University, East Lansing, MI, USA

    J C Anthony

  4. Department of Family and Community Health, University of Maryland School of Nursing, Baltimore, MD, USA

    C L Storr

  5. Department of Psychiatry and Center for Nicotine and Smoking Cessation Research, Duke University, Durham, NC, USA

    C L Storr, F M Behm & J E Rose

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  1. G R Uhl
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Correspondence to G R Uhl.

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Competing interests

Drs Rose and Uhl are listed as inventors for a patent application filed by Duke University based on genomic markers that distinguish successful quitters from unsuccessful quitters in data from other clinical trials.

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Uhl, G., Walther, D., Musci, R. et al. Smoking quit success genotype score predicts quit success and distinct patterns of developmental involvement with common addictive substances. Mol Psychiatry 19, 50–54 (2014). https://doi.org/10.1038/mp.2012.155

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