What you carry at this position in your DNA and what research says about it.
Nicotine Dependence Risk: 5/10 evidence, 13 publications.
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Sample genotype (not yours): T/T
Highest Risk of Nicotine Dependence and Lung Cancer
Inheriting the T/T genotype leads to the highest expression of nicotinic receptors. This is strongly associated with an increased risk of nicotine dependence and lung cancer.
What this genotype means: Highest risk of nicotine dependence; Highest risk of lung cancer; Higher success with nicotine replacement therapy.
Sample genotype (not yours): C/C
Lower Risk of Nicotine Dependence and Lung Cancer
Inheriting the C/C genotype is associated with lower expression of nicotinic receptors. This translates to a reduced risk of developing nicotine dependence and a lower risk of lung cancer.
What this genotype means: Lower risk of nicotine dependence; Lower risk of lung cancer; Delayed Parkinson's onset in smokers.
Sample genotype (not yours): T/C
Higher Risk of Nicotine Dependence and Lung Cancer
Presence of the T allele increases nicotinic receptor expression. This is linked to an increased risk of nicotine dependence and a higher risk of lung cancer.
What this genotype means: Increased risk of nicotine dependence; Higher risk of lung cancer; Higher success with nicotine replacement therapy.
Gene function and biological role
Gene Function: The CHRNA5 gene encodes the alpha-5 subunit of the nicotinic acetylcholine receptor, which is widely expressed in the brain and peripheral tissues. This receptor plays a critical role in mediating the effects of nicotine, the addictive component of tobacco smoke. Genetic variations in this gene cluster on chromosome 15 are strongly linked to smoking behaviors, nicotine dependence, and smoking-related diseases [1]. Studies show that altering the expression or structure of these receptors directly impacts how the brain responds to nicotine exposure [2].
Variant Impact: Altering the expression levels of the CHRNA5 nicotinic receptor subunit is the primary functional effect of this intronic variant. This specific genetic change acts as an expression quantitative trait locus, meaning it regulates how much CHRNA5 messenger RNA is produced in brain and lung tissues [2]. The minor T allele is associated with a two- to three-fold increase in CHRNA5 expression levels compared to the major C allele [3]. This variation in receptor expression levels is a key mechanism that influences susceptibility to nicotine dependence and lung cancer [4].
Key Insight: This variant acts as a genetic volume knob, where the T allele increases the expression of nicotinic receptors in the brain by up to three-fold.
Location: CHRNA5. Chromosome 15 · 15q25.1 · 78.6 Mb
Estimated prevalence by population
Global 13.1%; European 17.9%; African 9.0%; East Asian 3.2%; South Asian 10.9%; Americas 6.5%; Ashkenazi 14.0%; Finnish 14.0%; Middle Eastern 5.2%; Amish 18.8%.
Estimated TT genotype frequency.
Global 44.8%; European 48.8%; African 42.0%; East Asian 29.4%; South Asian 44.2%; Americas 38.0%; Ashkenazi 46.9%; Finnish 46.8%; Middle Eastern 35.2%; Amish 49.1%.
Estimated TC genotype frequency.
Global 42.1%; European 33.3%; African 49.1%; East Asian 67.4%; South Asian 44.9%; Americas 55.5%; Ashkenazi 39.1%; Finnish 39.1%; Middle Eastern 59.6%; Amish 32.1%.
Estimated CC genotype frequency.
Showing effects for T/T genotype
Neurology & Mental Health
Addiction & Reward
Nicotine Dependence. Evidence: 5/10. Source: PMID 19443489. Increased Risk.
Smoking Cessation. Evidence: 5/10. Source: PMID 24733007. Higher Success.
Neurodegenerative Diseases
Age of Parkinson's Onset. Evidence: 3/10. Source: PMID 22884254. Typical Onset.
Cancer & Oncology
Lung Cancer
Lung Cancer. Evidence: 4/10. Source: PMID 19443489. Increased Risk.
Immunity & Inflammation
Chronic Inflammatory Diseases
Crohn's Surgery Risk. Evidence: 3/10. Source: PMID 29052254. Increased Risk.
Showing effects for C/C genotype
Nicotine Dependence. Evidence: 5/10. Source: PMID 19443489. Typical Risk.
Smoking Cessation. Evidence: 5/10. Source: PMID 24733007. Typical Success.
Age of Parkinson's Onset. Evidence: 3/10. Source: PMID 22884254. Delayed Onset.
Lung Cancer. Evidence: 4/10. Source: PMID 19443489. Typical Risk.
Crohn's Surgery Risk. Evidence: 3/10. Source: PMID 29052254. Typical Risk.
Showing effects for T/C genotype
What this genotype means for the people who carry it
Sample genotype: TT (Homozygous)
A two- to three-fold increase in the expression of the CHRNA5 nicotinic receptor subunit occurs with the T/T genotype [1]. This high expression level is strongly linked to an increased susceptibility to nicotine dependence and heavy smoking [2]. Consequently, individuals with this genotype face a significantly higher risk of developing lung cancer, especially if they smoke [3]. On the positive side, T/T carriers have a higher likelihood of successfully quitting smoking when using nicotine replacement therapies like nicotine gum [4]. However, for Crohn's disease patients who smoke, this genotype is associated with an accelerated time to first surgery and a higher overall number of surgeries [5].
Highest risk of nicotine dependence; Highest risk of lung cancer; Higher success with nicotine replacement therapy.
Sample genotype: CC (Homozygous)
Baseline expression of the CHRNA5 nicotinic receptor subunit is lower in the brain and lungs for those with the C/C genotype [1]. This lower expression level is associated with a significantly reduced risk of nicotine dependence and heavy smoking [2]. Furthermore, because of the reduced receptor expression, individuals with this genotype have a lower risk of developing lung cancer [3]. In smokers, this genotype is also associated with a delayed age at onset of Parkinson's disease, possibly due to differences in how nicotine interacts with dopaminergic pathways [4]. Finally, Crohn's disease patients who smoke and carry this genotype have a lower risk of requiring multiple surgeries [5].
Lower risk of nicotine dependence; Lower risk of lung cancer; Delayed Parkinson's onset in smokers.
Sample genotype: TC (Heterozygous)
Intermediate to high expression of the CHRNA5 nicotinic receptor subunit occurs in brain and lung tissues with the T/C genotype [1]. This increased expression is associated with a higher risk of developing nicotine dependence and transitioning to heavy smoking [2]. The elevated receptor levels also contribute to a higher risk of lung cancer, particularly in individuals who smoke [3]. However, during smoking cessation attempts, carriers of the T allele show an increased likelihood of successfully quitting when using nicotine replacement therapy [4]. In Crohn's disease patients who smoke, this genotype is linked to an increased risk of requiring surgical interventions [5].
Increased risk of nicotine dependence; Higher risk of lung cancer; Higher success with nicotine replacement therapy.
Variants with shared genetic architecture
rs17486278 · CHRNA5 Gene · Chr 15 · Lung Disease Risk
rs55781567 · CHRNA5 Gene · Chr 15 · Lung Cancer Risk
rs16969968 · CHRNA5 Gene · Chr 15 · Nicotine Dependence Risk
Nicotinic receptor gene variants influence susceptibility to heavy smoking.
Nicotinic acetylcholine receptor variation and response to smoking cessation therapies.
Content updated August 2026.
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