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Genome-wide single nucleotide polymorphism heritability of nicotine dependence as a multidimensional phenotype

  • L. C. Bidwell (a1) (a2) (a3), R. H. C. Palmer (a2) (a3), L. Brick (a3), J. E. McGeary (a2) (a3) (a4) and V. S. Knopik (a2) (a3)...

Abstract

Background

Heritability estimates from twin studies of the multi-faceted phenotype of nicotine dependence (ND) range from moderate to high (31–60%), but vary substantially based on the specific ND-related construct examined. The current study estimated the aggregate role of common genetic variants on key ND constructs.

Method

Genomic-relationship-matrix restricted maximum likelihood (GREML) was used to decompose phenotypic variance across multiple ND indices using 796 125 polymorphisms from 2346 unrelated ‘lifetime ever smokers’ of European ancestry. Measures included DSM-IV ND and Fagerström Test for Nicotine Dependence (FTND) summary measures and constituent constructs (e.g. withdrawal severity, tolerance, heaviness of smoking and time spent smoking). Exploratory and confirmatory factor models were used to describe the covariance structure across ND measures; resulting factor(s) were the subject(s) of GREML analyses.

Results

Factor models indicated highly correlated DSM-IV and FTND factors for ND (0.545, 95% confidence interval 0.50–0.60) that could be represented as a higher-order factor (NIC DEP). Additive genetic influence on NIC DEP was 33% (s.e. = 0.14, p = 0.009). Post-hoc analyses indicated moderate genetic effects on the DSM-IV (34%, s.e. = 0.14, p = 0.008) and FTND (26%, s.e. = 0.14, p = 0.032) factors, both of which were influenced by the same genetic effects (r G-SNP = 1.00, s.e. = 0.09, p < 0.00001).

Conclusions

Overall, common single nucleotide polymorphisms accounted for a large proportion of the genetic influences on ND-related phenotypes that have been observed in twin studies. Genetic contributions across distinct ND scales were largely influenced by shared genetic factors.

Copyright

Corresponding author

*Address for correspondence: L. C. Bidwell, Ph.D., Institute of Cognitive Science, UCB 344, Boulder, CO 80309, USA. (Email: lcb@colorado.edu)

References

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American Psychiatric Association (1987). Diagnostic and Statistical Manual of Mental Disorders: DSM-III-R, 3rd revised edition. American Psychiatric Association: Washington, DC.
American Psychiatric Association (1994). Diagnostic and Statistical Manual of Mental Disorders: DSM-IV, 4th edition. American Psychiatric Association: Washington, DC.
Baker, TB, Weiss, RB, Bolt, D, von Niederhausern, A, Fiore, MC, Dunn, DM, Piper, ME, Matsunami, N, Smith, SS, Coon, H, McMahon, WM, Scholand, MB, Singh, N, Hoidal, JR, Kim, S-Y, Leppert, MF, Cannon, DS (2009). Human neuronal acetylcholine receptor A5-A3-B4 haplotypes are associated with multiple nicotine dependence phenotypes. Nicotine and Tobacco Research 11, 785796.
Bloom, AJ, Hartz, SM, Baker, TB, Chen, L, Piper, ME, Fox, L, Martinez, M, Hatsukami, D, Johnson, EO, Laurie, CC, Saccone, NL, Goate, A, Bierut, LJ (2014). Beyond cigarettes per day. A genome-wide association study of the biomarker carbon monoxide. Annals of the American Thoracic Society 11, 10031010.
Breslau, N, Johnson, EO (2000). Predicting smoking cessation and major depression in nicotine-dependent smokers. American Journal of Public Health 90, 11221127.
Broms, U, Silventoinen, K, Madden, PAF, Heath, AC, Kaprio, J (2006). Genetic architecture of smoking behavior: a study of Finnish adult twins. Twin Research and Human Genetics 9, 6472.
Bucholz, KK, Cadoret, R, Cloninger, CR, Dinwiddie, SH, Hesselbrock, VM, Nurnberger, JI, Reich, T, Schmidt, I, Schuckit, MA (1994). A new, semi-structured psychiatric interview for use in genetic linkage studies: a report on the reliability of the SSAGA. Journal of Studies on Alcohol 55, 149158.
Cheung, GW, Rensvold, RB (2002). Evaluating goodness-of-fit indexes for testing measurement invariance. Structural Equation Modeling 9, 233255.
Dijkstra, A, Tromp, D (2002). Is the FTND a measure of physical as well as psychological tobacco dependence? Journal of Substance Abuse Treatment 23, 367374.
Edwards, AC, Maes, HH, Pedersen, NL, Kendler, KS (2011). A population-based twin study of the genetic and environmental relationship of major depression, regular tobacco use and nicotine dependence. Psychological Medicine 41, 395405.
Golden Helix, Inc. (2016). SNP & Variation Suite, version 8.3.4 (http://www.goldenhelix.com). Accessed January 2016.
Hancock, DB, Reginsson, GW, Gaddis, NC, Chen, X, Saccone, NL, Lutz, SM, Qaiser, B, Sherva, R, Steinberg, S, Zink, F, Stacey, SN, Glasheen, C, Chen, J, Gu, F, Frederiksen, BN, Loukola, A, Gudbjartsson, DF, Bruske, I, Landi, MT, Bickeboller, H, Madden, P, Farrer, L, Kaprio, J, Kranzler, HR, Gelernter, J, Baker, TB, Kraft, P, Amos, CI, Caporaso, NE, Hokanson, JE, Bierut, LJ, Thorgeirsson, TE, Johnson, EO, Stefansson, K (2015). Genome-wide meta-analysis reveals common splice site acceptor variant in CHRNA4 associated with nicotine dependence. Translational Psychiatry 5, e651.
Heatherton, TF, Kozlowski, LT, Frecker, RC, Rickert, W, Robinson, J (1989). Measuring the heaviness of smoking: using self-reported time to the first cigarette of the day and number of cigarettes smoked per day. British Journal of Addiction 84, 791800.
Hettema, JM, Corey, LA, Kendler, KS (1999). A multivariate genetic analysis of the use of tobacco, alcohol, and caffeine in a population based sample of male and female twins. Drug and Alcohol Dependence 57, 6978.
Hudmon, KS, Marks, JL, Pomerleau, CS, Bolt, DM, Brigham, J, Swan, GE (2003). A multidimensional model for characterizing tobacco dependence. Nicotine and Tobacco Research 5, 655664.
Hughes, JR (2003). The case for hardening the target. In Those Who Continue to Smoke: Is Achieving Abstinence Harder and Do We Need to Change Our Interventions? Smoking and Tobacco Control Monograph no. 15. NIH publication no. 03-5370. Department of Health and Human Services, Public Health Service, National Institutes of Health, National Cancer Institute: Bethesda, MD.
Hughes, JR, Oliveto, AH, Riggs, R, Kenny, M, Liguori, A, Pillitteri, JL, MacLaughlin, MA (2004). Concordance of different measures of nicotine dependence: two pilot studies. Addictive Behaviors 29, 15271539.
Kandel, D, Schaffran, C, Griesler, P, Samuolis, J, Davies, M, Galanti, R (2005). On the measurement of nicotine dependence in adolescence: comparisons of the mFTQ and a DSM-IV-based scale. Journal of Pediatric Psychology 30, 319332.
Kaprio, JA, Koskenvuo, M, Sarna, S (1981). Cigarette smoking, use of alcohol, and leisure-time physical activity among same-sexed adult male twins. Progress in Clinical and Biological Research 69, 3746.
Koob, GF, Volkow, ND (2010). Neurocircuitry of addiction. Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology 35, 217238.
Koopmans, J, Slutske, W, Heath, A, Neale, M, Boomsma, D (1999). The genetics of smoking initiation and quantity smoked in Dutch adolescent and young adult twins. Behavior Genetics 29, 383393.
Lee, SH, Yang, J, Goddard, ME, Visscher, PM, Wray, NR (2012). Estimation of pleiotropy between complex diseases using single-nucleotide polymorphism-derived genomic relationships and restricted maximum likelihood. Bioinformatics 28, 25402542.
Lessov, CN, Martin, NG, Statham, DJ, Todorov, AA, Slutske, WS, Bucholz, KK, Heath, AC, Madden, PAF (2004). Defining nicotine dependence for genetic research: evidence from Australian twins. Psychological Medicine 34, 865879.
Loukola, A, Wedenoja, J, Keskitalo-Vuokko, K, Broms, U, Korhonen, T, Ripatti, S, Sarin, A-P, Pitkäniemi, J, He, L, Häppölä, A, Heikkilä, K, Chou, Y-L, Pergadia, ML, Heath, AC, Montgomery, GW, Martin, NG, Madden, PAF, Kaprio, J (2014). Genome-wide association study on detailed profiles of smoking behavior and nicotine dependence in a twin sample. Molecular Psychiatry 19, 615624.
MacCallum, RC, Browne, MW, Sugawara, HM (1996). Power analysis and determination of sample size for covariance structure modeling. Psychological Methods 1, 130149.
McGue, M, Elkins, I, Iacono, WG (2000). Genetic and environmental influences on adolescent substance use and abuse. American Journal of Medical Genetics 96, 671677.
Moolchan, ET, Radzius, A, Epstein, DH, Uhl, G, Gorelick, DA, Cadet, JL, Henningfield, JE (2002). The Fagerstrom Test for Nicotine Dependence and the Diagnostic Interview Schedule: do they diagnose the same smokers? Addictive Behaviors 27, 101113.
National Cancer Institute (2009). Phenotypes and Endophenotypes: Foundations for Genetic Studies of Nicotine Use and Dependence. Tobacco Control Monograph no. 20. NIH publication no. 09-6366. US Department of Health and Human Services, National Institutes of Health, National Cancer Institute: Bethesda, MD.
National Center for Biotechnology Information (2016). Study of Addiction: Genetics and Environment (SAGE) (http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000092.v1.p1). Accessed January 2016.
Olfson, E, Saccone, NL, Johnson, EO, Chen, LS, Culverhouse, R, Doheny, K, Foltz, SM, Fox, L, Gogarten, SM, Hartz, S, Hetrick, K, Laurie, CC, Marosy, B, Amin, N, Arnett, D, Barr, RG, Bartz, TM, Bertelsen, S, Borecki, IB, Brown, MR, Chasman, DI, van Duijn, CM, Feitosa, MF, Fox, ER, Franceschini, N, Franco, OH, Grove, ML, Guo, X, Hofman, A, Kardia, SLR, Morrison, AC, Musani, SK, Psaty, BM, Rao, DC, Reiner, AP, Rice, K, Ridker, PM, Rose, LM, Schick, UM, Schwander, K, Uitterlinden, AG, Vojinovic, D, Wang, JC, Ware, EB, Wilson, G, Yao, J, Zhao, W, Breslau, N, Hatsukami, D, Stitzel, JA, Rice, J, Goate, A, Bierut, LJ (2015). Rare, low frequency and common coding variants in CHRNA5 and their contribution to nicotine dependence in European and African Americans. Molecular Psychiatry. Published online 4 August 2015. doi:10.1038/mp.2015.105.
Palmer, RHC, Brick, L, Nugent, NR, Bidwell, LC, McGeary, JE, Knopik, VS, Keller, MC (2015 a). Examining the role of common genetic variants on alcohol, tobacco, cannabis and illicit drug dependence: genetics of vulnerability to drug dependence. Addiction 110, 530537.
Palmer, RHC, McGeary, JE, Heath, AC, Keller, MC, Brick, LA, Knopik, VS (2015 b). Shared additive genetic influences on DSM-IV criteria for alcohol dependence in subjects of European ancestry. Addiction 110, 19221931.
Payne, TJ, Smith, PO, McCracken, LM, McSherry, WC, Antony, MM (1994). Assessing nicotine dependence: a comparison of the Fagerström Tolerance Questionnaire (FTQ) with the Fagerström Test for Nicotine Dependence (FTND) in a clinical sample. Addictive Behaviors 19, 307317.
Pergadia, M, Heath, A, Agrawal, A, Bucholz, K, Martin, N, Madden, PF (2006 a). The implications of simultaneous smoking initiation for inferences about the genetics of smoking behavior from twin data. Behavior Genetics 36, 567576.
Pergadia, ML, Heath, AC, Martin, NG, Madden, PAF (2006 b). Genetic analyses of DSM-IV nicotine withdrawal in adult twins. Psychological Medicine 36, 963972.
Piper, ME, McCarthy, DE, Baker, TB (2006). Assessing tobacco dependence: a guide to measure evaluation and selection. Nicotine and Tobacco Research 8, 339351.
Piper, ME, Piasecki, TM, Federman, EB, Bolt, DM, Smith, SS, Fiore, MC, Baker, TB (2004). A multiple motives approach to tobacco dependence: the Wisconsin Inventory of Smoking Dependence Motives (WISDM-68). Journal of Consulting and Clinical Psychology 72, 139154.
Pomerleau, OF, Collins, AC, Shiffman, S, Pomerleau, CS (1993). Why some people smoke and others do not: new perspectives. Journal of Consulting and Clinical Psychology 61, 723731.
Shiffman, S, Waters, AJ, Hickcox, M (2004). The Nicotine Dependence Syndrome Scale: a multidimensional measure of nicotine dependence. Nicotine and Tobacco Research 6, 327348.
Stanton-Geddes, J, Yoder, JB, Brikine, R, Young, ND, Tiffin, P (2013). Estimating heritability using genomic data. Methods in Ecology and Evolution 4, 11511158.
Swan, GE, Carmelli, D, Cardon, LR (1997). Heavy consumption of cigarettes, alcohol and coffee in male twins. Journal of Studies on Alcohol 58, 182190.
Swan, GE, Carmelli, D, Rosenman, RH, Fabsitz, RR, Christian, JC (1990). Smoking and alcohol consumption in adult male twins: genetic heritability and shared environmental influences. Journal of Substance Abuse 2, 3950.
True, WR, Xian, H, Scherrer, JF, Madden, PAF, Bucholz, KK, Heath, AC, Eisen, SA, Lyons, MJ, Goldberg, J, Tsuang, M (1999). Common genetic vulnerability for nicotine and alcohol dependence in men. Archives of General Psychiatry 56, 655661.
Vrieze, SI, Feng, S, Miller, MB, Hicks, BM, Pankratz, N, Abecasis, GR, Iacono, WG, McGue, M (2014). Rare nonsynonymous exonic variants in addiction and behavioral disinhibition. Biological Psychiatry 75, 783789.
Vrieze, SI, McGue, M, Miller, MB, Hicks, BM, Iacono, WG (2013). Three mutually informative ways to understand the genetic relationships among behavioral disinhibition, alcohol use, drug use, nicotine use/dependence, and their co-occurrence: twin biometry, GCTA, and genome-wide scoring. Behavior Genetics 43, 97107.
Yang, J, Benyamin, B, McEvoy, BP, Gordon, S, Henders, AK, Nyholt, DR, Madden, PA, Heath, AC, Martin, NG, Montgomery, GW, Goddard, ME, Visscher, PM (2010). Common SNPs explain a large proportion of the heritability for human height. Nature Genetics 42, 565569.
Yang, J, Lee, S, Goddard, M, Visscher, P (2013). Genome-wide complex trait analysis (GCTA): methods, data analyses, and interpretations. In Genome-Wide Association Studies and Genomic Prediction (ed. Gondro, C., van der Werf, J. and Hayes, B.), pp. 215236. Humana Press: New York.

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Genome-wide single nucleotide polymorphism heritability of nicotine dependence as a multidimensional phenotype

  • L. C. Bidwell (a1) (a2) (a3), R. H. C. Palmer (a2) (a3), L. Brick (a3), J. E. McGeary (a2) (a3) (a4) and V. S. Knopik (a2) (a3)...

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