5.3 Early biological factors

Last updated April 2012

5.3.1 Genetics

Greater understanding of the human genome has led to enquiry into whether genetics can affect an individual's chances of becoming an established smoker. Data from family, adoption and in particular twin studies have suggested that genetic makeup could contribute to the likelihood of both experimentation and progression to established patterns of smoking.1–5 In 2010, the US Surgeon General reported that 'genes appear to predispose persons to smoking initiation and persistence and possibly are related to the extent of difficulty a person has in smoking cessation'.6(page 156) Twin studies have variously reported that heritability for smoking (that is to say, the proportion in the variance in smoking that is attributable to genetic factors) ranges from around 50–80%, which is in keeping with heritability estimates for alcoholism, asthma and hypertension.3

While inherited factors influencing initiation and dependence are likely to overlap to some degree, there is evidence that independent genetic influences may mediate each stage of tobacco use.2 ,7–9 For example, one review of the data has estimated that, in twins, around 60% of the liability to initiate smoking can be attributed to genetic influences.1 However, environmental influences10 obviously also play an important role in nicotine dependence and frequency of smoking,6, 11 and genetic predisposition to tobacco use may be modified by individual and environmental factors such as family structure, religion and marital status.2

Interactions between genetic and environmental influence, and the causes of the relationships between social risk factors and substance use, may change significantly over the course of development. For example, some recent evidence from twin research found that as twins developed from childhood to adulthood, the influence of shared environmental factors on church attendance (a consistent predictor of nicotine and alcohol consumption) declined dramatically, while the role of genetic factors increased.5 Frequent church attendance in adolescence appeared to reflect a range of shared familial and social–environmental influences that were protective against substance use, while in adulthood the inverse relationship between church attendance and substance use became stronger, stemming largely from genetically influenced temperamental factors.5

Genetic influences may mediate the association between social factors (such as adolescents' peer characteristics, including peer smoking) and smoking behaviour (including nicotine dependence) in other ways;10, 12 for example, adolescents with specific genetic risk for nicotine dependence may be less affected by social context such as peer smoking than those with lower risk genotypes.12 The evidence regarding potential gender differences in the relative importance of genetic and shared environmental influences for adolescent smoking behaviour and nicotine dependence is mixed,6, 13 while the extent of interaction between environmental and genetic risk factors in increasing susceptibility to nicotine addiction is unknown.14

Smoking is understood to be a highly complex behaviour, and where a genetic basis is postulated, it is with the recognition that many genes are likely to be involved, each individually contributing only a small degree of influence. Candidate genes for investigation in tobacco initiation, dependence and persistence have included several known to affect neurotransmitter pathways, nicotine-specific pathways and nicotine metabolism.2 The inheritance of genetic material may include polymorphisms of such genes, affecting individuals' physiological responses to nicotine, such as the rate of nicotine metabolism, receptor sensitivity to nicotine and to certain neurotransmitters, and the levels of neurotransmitters available at neural synapses. These individual differences in response to nicotine are likely to affect the trajectory toward the development of nicotine dependence.6 Other genes connected with traits such as depression and anxiety are also being studied.2 There is also emerging evidence that genetic factors may influence an individual's choice of friends, and that some individuals' genetic makeup may make them more susceptible to the influence of peer groups.15

Baler and Volkow13 describe the power of genetic variations, even at the level of a single gene, to affect performance in key behavioural circuits and subsequently impact on addiction risk. Behavioural circuits are being developed constantly due to interaction between genes and experience, resulting in the formation of attitudes, temperaments and, often, fixed behavioural patterns. During this maturation there are numerous opportunities to introduce risk or resilience into the system, as so many complex and overlapping developmental processes are taking place; this will influence subsequent individual tendencies such as those towards risk taking, for example.13

The role of genes in smoking behaviour is discussed further in Chapter 6, Section 4.

5.3.2 Effect of maternal smoking in utero on uptake of smoking in offspring

Several studies from Australia16,17 and internationally18–22 have reported an association between smoking during pregnancy and subsequent increased likelihood of uptake of smoking in offspring, even after controlling for a range of confounding factors. It may be that effects are different depending on the sex of the baby, with some research suggesting that female offspring exposed to tobacco smoke prenatally are more susceptible to taking up smoking as adolescents than male offspring similarly exposed.22

The relationship between maternal smoking and subsequent smoking uptake by offspring might be partially explained by their shared genetic background.6 Mothers who continue to smoke after pregnancy may also affect children's attitude to smoking through role modelling.6 Findings of at least one study suggest that the effects of maternal smoking may not persist beyond early adolescence, after which social factors (such as mother's current smoking behaviour and peer smoking) appear to become more important.23

However a connection between maternal smoking and in utero effects on the brain is physiologically plausible. While the exact mechanisms and long-term consequences of these effects have not been fully elucidated24 it is known that nicotine (a toxic chemical) present in tobacco smoke reaches the unborn child through the placenta, binding with and activating neurotransmitters in the central and peripheral nervous system and negatively affecting neurodevelopment. Chronic exposure to nicotine during prenatal development has been shown in some animal studies to affect reward-related neural circuitry, in turn modifying the psychoactive effects of drugs in later life.25 A recent behavioural study among Canadian adolescents found that participants who had been prenatally exposed to maternal tobacco smoke were significantly more likely to use an addictive substance later in life, even after controlling for other variables such as age and peer drug use.25 Investigators suggested that prenatal exposure to maternal smoking could interfere with cortical development (important in decision-making) via modification of the gene that produced 'brain-derived neurotrophic factor' (BDNF); this in turn could influence adolescent susceptibility to addiction through abnormal processing of reward-associated cues, facilitating impulsive behaviours and subsequently higher substance abuse rates.13, 25

5.3.3 Exposure to secondhand smoke

While exposure to secondhand smoke (SHS) has long been known to cause serious diseases6, it has also been associated in a few recent studies with increased risk for initiation and maintenance of cigarette smoking,26–28 including experiencing nicotine dependence-related symptoms.27, 28 Non-smokers exposed to high levels of SHS may absorb amounts of nicotine similar to smokers.28 For example, recent research examining the effects of SHS exposure on nicotinic acetylcholine receptors in the brain found that both smoking and non-smoking participants who were exposed to SHS for one hour as car passengers experienced significant receptor occupancy and increased plasma nicotine concentrations.26

A recent exploratory US study investigated whether sensitivity to SHS exposure (assessed with reaction measures commonly used to gauge subjective reactivity to the first experience with smoking cigarettes) among never-smokers aged 8–13 years predicted susceptibility to smoking (measured through likelihood of future smoking).27 Those who reported more negative experiences with SHS exposure (such as coughing or feeling sick) tended to be less susceptible to smoking than those who experienced fewer unpleasant reactions. Some evidence was found for decreasing sensitivity to SHS with age.27 Children are especially susceptible to the effects of nicotine exposure through SHS, in part due to the differing effects of nicotine pharmacokinetics between children and adults.28

Exposure to smoke in social situations (quantified as the number of current smokers in the social environment and number of situations where SHS exposure occurs), has been found to predict precursors to smoking initiation (including perceived nicotine dependence and smoking susceptibility) among adolescent never-smokers.28

A large 2011 US survey involving students aged 12–17 years found exposure to secondhand smoke (as measured by frequency of exposure during the previous week and smoking in the home) was as influential in prompting uptake of smoking as peer pressure and exposure to tobacco advertising.29

In addition to a shared genetic predisposition to smoke and role modelling of smoking behaviour,28 cumulative exposure to secondhand smoke may increase risk for smoking uptake through additional exposure to nicotine during a time of critical brain development.27

5.3.4 Childhood illness and smoking uptake

The occurrence of asthma during childhood may be associated with reduced smoking uptake among male adolescents, but not females.30 Illness outcomes such as quality of life (QOL) and smoking have been shown to be related in studies among healthy and illness populations.31 The assumption that smoking causes a reduction in QOL was supported in some longitudinal studies, while other longitudinal research found that changes in smoking status did not predict QOL changes.31 A longitudinal study investigating whether the outcomes of asthma predicted smoking onset among adolescents with asthma found that poorer self-reported medication adherence and the maladaptive coping strategy of hiding asthma predicted smoking onset among both girls and boys, while poorer QOL predicted smoking in boys only.31 There is some evidence of an indirect relationship between asthma and smoking behaviour from a prospective population-based study conducted among almost 6000 Dutch adolescents in two waves 22 to 24 months apart. Participants with current asthma were more likely to report depressive feelings (as opposed to depression or depressive symptoms) than those without asthma: specifically, those with current, severe symptoms of asthma were more likely to report depressive feelings than respondents with mild and moderate symptoms. However, smoking behaviour was similar for adolescents with and without asthma. Depressive feelings and smoking were related both cross-sectionally and longitudinally.32

There is a strong relationship between adolescent smoking and a range of psychiatric conditions; these are discussed further in Section 5.5.2.

Recent news and research

For recent news items and research on this topic, click here (Last updated March 2018)  


1. Sullivan P and Kendler K. The genetic epidemiology of smoking. Nicotine & Tobacco Research 1999;1(suppl.1):i51-7. Available from: http://ntr.oxfordjournals.org/content/1/Suppl_1

2. Lerman C and Berrettini W. Elucidating the role of genetic factors in smoking behaviour and nicotine dependence. American Journal of Medical Genetics (Neuropsychiatric Genetics) 2003;118B:48-54. Available from: http://www.ncbi.nlm.nih.gov/pubmed/12627466

3. Batra V, Patkar A, Berrettini W, Weinstein S and Leone F. The genetic determinants of smoking. Chest 2003;123(5):1730-39. Available from: http://www.chestjournal.org/cgi/content/abstract/123/5/1730

4. Hall W, Madden P and Lynskey M. The genetics of tobacco use: methods, findings and policy implications. Tobacco Control 2002;11:119-24. Available from: http://tobaccocontrol.bmj.com/cgi/reprint/11/2/119.pdf

5. Kendler K and Myers J. A developmental twin study of church attendance and alcohol and nicotine consumption: a model for analyzing the changing impact of genes and environment. The American Journal of Psychiatry 2009;166(10):1150–5. Available from: http://ajp.psychiatryonline.org/cgi/content/full/166/10/1150

6. US Department of Health and Human Services. How tobacco smoke causes disease: the biology and behavioral basis for smoking-attributable disease: a report of the Surgeon General. Atlanta, Georgia: US Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, 2010. Available from: http://www.cdc.gov/tobacco/data_statistics/sgr/2010/index.htm

7. Kendler K, Neale M, Sullivan P, Corey L, Gardner C and Prescott C. A population-based twin study in women of smoking initiation and nicotine dependence. Psychological Medicine 1999;29:299-308. Available from: http://www.ncbi.nlm.nih.gov/pubmed/10218922

8. Maes H, Sullivan P, Bulik C, Neale M, Prescott C and Eaves L. A twin study of genetic and environmental influences on tobacco initiation, regular tobacco use and nicotine dependence. Psychological Medicine 2004;34:1251-61. Available from: http://www.ncbi.nlm.nih.gov/pubmed/15697051

9. Vink J, Willemsen G and Boomsma D. Heritability of smoking initiation and nicotine dependence. Behavioral Genetics 2005;35:397-406. Available from: http://www.ncbi.nlm.nih.gov/pubmed/15971021

10. Harakeh Z, Neiderhiser J, Spotts E, Engels R, Scholte R and Reiss D. Genetic factors contribute to the association between peers and young adults smoking: univariate and multivariate behavioral genetic analyses. Addictive Behaviors 2008;33(9):1113–22. Available from: http://www.ncbi.nlm.nih.gov/pubmed/18584970

11. Agrawal A, Balasubramanian S, Smith E, Madden P, Bucholz K, Heath A, et al. Peer substance involvement modifies genetic influences on regular substance involvement in young women. Addiction 2010;105(10):1844–53. Available from: http://onlinelibrary.wiley.com/doi/10.1111/j.1360-0443.2010.02993.x/full

12. Johnson E, Chen L, Breslau N, Hatsukami D, Robbins T, Saccone N, et al. Peer smoking and the nicotinic receptor genes: an examination of genetic and environmental risks for nicotine dependence. Addiction 2010;105(11):2014-22. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20840187

13. Baler R and Volkow N. Addiction as a systems failure: focus on adolescence and smoking. Journal of the American Academy of Child & Adolescent Psychiatry 2011;50(4):329–39. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21421173

14. Swan GE. Implications of genetic epidemiology for the prevention of tobacco use. Nicotine & Tobacco Research 1999;1(suppl.1):S49-56. Available from: http://ntr.oxfordjournals.org/content/1/Suppl_1/S49.abstract

15. Harden K, Hill J, Turkheimer E and Emery R. Gene-environment correlation and interaction in peer effects on adolescent alcohol and tobacco use. Behavioral Genetics 2008;38:339-47. Available from: http://www.ncbi.nlm.nih.gov/pubmed/18368474

16. Al Mamun A, Lawlor D, Alati R, O'Callaghan M, Williams G and Najman J. Does maternal smoking during pregnancy have a direct effect on future offspring obesity? Evidence from a prospective birth cohort study. American Journal of Epidemiology 2006;164(4):317–25. Available from: http://aje.oxfordjournals.org/cgi/content/full/164/4/317

17. O'Callaghan F, O'Callaghan M, Najman J, Williams G, Bor W and Alati R. Prediction of adolescent smoking from family and social risk factors at 5 years, and maternal smoking in pregnancy and at 5 and 14 years. Addiction 2006;101(2):282-90. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16445557

18. Buka S, Shenassa E and Niaura R. Elevated risk of tobacco dependence among offspring of mothers who smoked during pregnancy: a 30-year prospective study. The American Journal of Psychiatry 2003;160:1978-84. Available from: http://ajp.psychiatryonline.org/cgi/content/full/160/11/1978

19. Oncken C, McKee S, Krishnan-Sarin S, O'Malley S and Mazure C. Gender effects of reported in utero tobacco exposure on smoking initiation, progression and nicotine dependence in adult offspring. Nicotine & Tobacco Research 2004;6(5):829-33. Available from: http://www.ncbi.nlm.nih.gov/pubmed/15700918

20. Lieb R, Schreier A, Pfister H and Wittchen H. Maternal smoking and smoking in adolescents: a prospective community study of adolescents and their mothers. European Addiction Research 2003;9(3):120-30. Available from: http://www.ncbi.nlm.nih.gov/pubmed/12837990

21. Porath A and Fried P. Effects of prenatal cigarette and marijuana exposure on drug use among offspring. Neurotoxicological Teratology 2005;27(2):267-77. Available from: http://www.ncbi.nlm.nih.gov/pubmed/15734278

22. Roberts K, Munafo M, Rodriguez D, Drury M, Murphy M and Neale R. Longitudinal analysis of the effect of prenatal nicotine exposure on subsequent smoking behaviour of offspring. Nicotine & Tobacco Research 2005;7(5):801-8. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16191751

23. Cornelius M, Leech S, Goldschmidt L and Day N. Is prenatal tobacco exposure a risk factor for early adolescent smoking? A follow-up study. Neurotoxicological Teratology 2005;27:667-76. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16014324

24. Shea A and Steiner M. Cigarette smoking during pregnancy. Nicotine & Tobacco Research 2008;10(2):267-78. Available from: http://www.ncbi.nlm.nih.gov/pubmed/18236291

25. Lotfipour S, Ferguson E, Leonard G, Perron M, Pike B, Richer L, et al. Orbitofrontal cortex and drug use during adolescence: role of prenatal exposure to maternal smoking and BDNF genotype. Archives of General Psychiatry 2009;66(11):1244. Available from: http://archpsyc.ama-assn.org/cgi/reprint/66/11/1244

26. Brody A, Mandelkern M, London E, Khan A, Kozman D, Costello M, et al. Effect of secondhand smoke on occupancy of nicotinic acetylcholine receptors in brain. Archives of General Psychiatry 2011;68(9):953-60. Available from: http://archpsyc.ama-assn.org/cgi/content/full/archgenpsychiatry.2011.51v1

27. Lessov-Schlaggar C, Wahlgren D, Liles S, Jones J, Ji M, Hughes S, et al. Sensitivity to secondhand smoke exposure predicts smoking susceptibility in 8-13-year-old never smokers. Journal of Adolescent Health 2011;48(3):234–40. Available from: http://www.jahonline.org/article/S1054-139X%2810%2900308-3/fulltext

28. Racicot S, McGrath J and O'Loughlin J. An investigation of social and pharmacological exposure to secondhand tobacco smoke as possible predictors of perceived nicotine dependence, smoking susceptibility, and smoking expectancies among never-smoking youth. Nicotine & Tobacco Research 2011;13(10):926-33. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21622492

29. Voorhees C, Ye C, Carter-Pokras O, MacPherson L, Kanamori M, Zhang G, et al. Peers, tobacco advertising, and secondhand smoke exposure influences smoking initiation in diverse adolescents. American Journal of Health Promotion 2011;25(3):e1–11. Available from: http://ajhpcontents.org/doi/full/10.4278/ajhp.090604-QUAN-180

30. Verlato G, Bortolami O, Accordini S, Olivieri M, Cappa V, Bugiani M, et al. Asthma in childhood reduces smoking initiation in subsequent teens among males. Journal of Adolescent Health 2011;48(3):253–8. Available from: http://www.jahonline.org/article/S1054-139X%2810%2900341-1/fulltext

31. Van De Ven M, Engels R and Sawyer S. Asthma-specific predictors of smoking onset in adolescents with asthma: a longitudinal study. Journal of Pediatric Psychology 2009;34(2):118. Available from: http://www.ncbi.nlm.nih.gov/pubmed/18567925

32. Otten R, Van de Ven M, Engels R and Van den Eijnden R. Depressive mood and smoking onset: a comparison of adolescents with and without asthma. Psychology & Health 2009;24(3):287–300. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20204994

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