What you carry at this position in your DNA and what research says about it.
Smoking and Lung Cancer Risk: 9/10 evidence, 20 publications.
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Sample genotype (not yours): G/G
Lower Risk of Nicotine Dependence
A lower tendency to become a heavy smoker is characteristic of this genotype. It also correlates with a lower baseline risk of developing lung cancer and chronic obstructive pulmonary disease.
What this genotype means: Lower risk of nicotine dependence; Lower risk of lung cancer; Typical response to smoking cessation drugs.
Sample genotype (not yours): A/A
Higher Risk of Nicotine Dependence
A higher tendency to become a heavy smoker is linked to this genotype. It also correlates with a significantly increased risk of lung cancer and chronic obstructive pulmonary disease.
What this genotype means: Higher risk of nicotine dependence; Significantly increased risk of lung cancer; Excellent response to smoking cessation drugs.
Sample genotype (not yours): G/A
Moderately Increased Risk of Nicotine Dependence
An average tendency to become a heavy smoker is associated with this genotype. It also carries a moderately increased risk of lung cancer and chronic lung diseases compared to the G/G genotype.
What this genotype means: Average to moderately increased risk of nicotine dependence; Increased risk of lung cancer; Better response to smoking cessation drugs.
Gene function and biological role
Gene Function: CHRNA5 encodes the cholinergic receptor nicotinic alpha 5 subunit, which forms part of the nicotinic acetylcholine receptors in the brain and lungs [1]. These receptors mediate fast signal transmission at synapses and respond directly to nicotine [1]. Variations in this gene cluster are heavily implicated in nicotine dependence, smoking quantity, and respiratory health [2]. Interestingly, these receptors are expressed not only in the central nervous system but also in bronchial epithelial cells, directly linking them to lung physiology [2].
Variant Impact: The rs2036527 variant is an intergenic single nucleotide polymorphism located in the CHRNA5-CHRNA3-CHRNB4 gene cluster on chromosome 15 [3]. It acts as a cis-regulatory variant, altering enhancer activity and regulating the expression levels of both CHRNA3 and CHRNA5 [3]. The A allele is associated with increased expression of these nicotinic receptor subunits, which influences how the brain processes nicotine [3] [1]. This regulatory change directly impacts susceptibility to heavy smoking and subsequent lung diseases [1].
Key Insight: This variant acts as a genetic dimmer switch, altering how much of the nicotine receptor is produced in the brain and lungs rather than changing the receptor's structure itself.
Location: CHRNA5. Chromosome 15 · 15q25.1 · 78.6 Mb
Estimated prevalence by population
Global 51.3%; European 42.3%; African 60.6%; East Asian 93.3%; South Asian 60.0%; Americas 57.7%; Ashkenazi 41.6%; Finnish 45.0%; Middle Eastern 35.0%; Amish 35.2%.
Estimated GG genotype frequency.
Global 39.8%; European 45.5%; African 34.5%; East Asian 6.6%; South Asian 34.9%; Americas 36.5%; Ashkenazi 45.8%; Finnish 44.2%; Middle Eastern 48.3%; Amish 48.3%.
Estimated GA genotype frequency.
Global 8.9%; European 12.2%; African 4.9%; East Asian 0.1%; South Asian 5.1%; Americas 5.8%; Ashkenazi 12.6%; Finnish 10.8%; Middle Eastern 16.7%; Amish 16.5%.
Estimated AA genotype frequency.
Showing effects for G/G genotype
Neurology & Mental Health
Addiction & Reward
Nicotine Dependence. Evidence: 6/10. Source: PMID 22832964. Lower Tendency.
Smoking Cessation Drug Response. Evidence: 5/10. Source: PMID 29621993. Typical Response.
Cancer & Oncology
Lung Cancer
Lung Cancer. Evidence: 9/10. Source: PMID 39366959. Typical Risk.
Organ Systems
Respiratory Health
Chronic Lung Disease. Evidence: 9/10. Source: PMID 39024449. Typical Risk.
Dental & Oral Health
Dental Caries. Evidence: 6/10. Source: PMID 39192244. Typical Risk.
Showing effects for A/A genotype
Nicotine Dependence. Evidence: 6/10. Source: PMID 22832964. Higher Tendency.
Smoking Cessation Drug Response. Evidence: 5/10. Source: PMID 29621993. Stronger Response.
Lung Cancer. Evidence: 9/10. Source: PMID 39366959. Higher Risk.
Chronic Lung Disease. Evidence: 9/10. Source: PMID 39024449. Higher Risk.
Dental Caries. Evidence: 6/10. Source: PMID 39192244. Higher Risk.
Showing effects for G/A genotype
Nicotine Dependence. Evidence: 6/10. Source: PMID 22832964. Average Tendency.
Lung Cancer. Evidence: 9/10. Source: PMID 39366959. Increased Risk.
Chronic Lung Disease. Evidence: 9/10. Source: PMID 39024449. Increased Risk.
Dental Caries. Evidence: 6/10. Source: PMID 39192244. Increased Risk.
What this genotype means for the people who carry it
Sample genotype: GG (Homozygous)
Research indicates that the G allele is protective against heavy smoking behaviors and nicotine dependence [1]. Synaptic transmission in the brain's reward pathways is less sensitive to nicotine cravings in those with this genotype [1]. Consequently, these individuals are less likely to consume large quantities of cigarettes per day [2]. This reduced exposure to tobacco smoke directly translates to a lower risk of lung cancer and chronic obstructive pulmonary disease [2]. Furthermore, pulmonary function measurements tend to be higher and more stable over time [3]. Dental health may also benefit, as there is a lower risk of dental caries associated with this genotype [4]. When attempting to quit smoking, standard cessation therapies like varenicline or bupropion show typical efficacy rates [5].
Lower risk of nicotine dependence; Lower risk of lung cancer; Typical response to smoking cessation drugs.
Sample genotype: AA (Homozygous)
Carrying two copies of the A allele is strongly linked to a high susceptibility for nicotine dependence and heavy smoking [1]. Enhanced expression of nicotinic receptor subunits in the brain increases the drive to smoke [1]. Individuals with this genotype tend to smoke significantly more cigarettes per day and have higher levels of cotinine, a nicotine metabolite [2]. This heavy exposure dramatically elevates the risk of developing lung cancer and lung adenocarcinoma [3]. It also significantly increases the risk of chronic obstructive pulmonary disease and chronic bronchitis [4]. On the positive side, clinical trials have shown that this genotype responds exceptionally well to smoking cessation therapies like varenicline and bupropion [5]. These medications can help overcome the strong genetic drive to smoke by targeting the highly active nicotinic receptors [5]. Additionally, there is an increased risk of dental caries associated with this genotype [6].
Higher risk of nicotine dependence; Significantly increased risk of lung cancer; Excellent response to smoking cessation drugs.
Sample genotype: GA (Heterozygous)
Having one copy of the A allele is associated with an average tendency to become a heavy smoker [1]. Nicotinic receptors in the brain show altered expression levels, which can increase the reinforcing effects of nicotine [1]. Studies show a moderate increase in the number of cigarettes smoked per day compared to the G/G genotype [2]. This increased tobacco exposure is linked to a higher risk of developing lung cancer, including lung adenocarcinoma [3]. Respiratory health may also be affected, with a higher likelihood of chronic bronchitis and reduced pulmonary function [4]. Interestingly, this genotype is associated with a better response to smoking cessation medications such as varenicline, bupropion, and nicotine replacement therapy [5]. This means that while the risk of dependence is higher, pharmacological support during quitting is often more effective [5]. Dental health should also be monitored, as there is a slightly elevated risk of dental caries [6].
Average to moderately increased risk of nicotine dependence; Increased risk of lung cancer; Better response to smoking cessation drugs.
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
Variants in nicotinic receptors and risk for nicotine dependence.
Nicotinic receptor gene variants influence susceptibility to heavy smoking.
Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function.
Genome-wide association meta-analysis identifies two novel loci associated with dental caries.
Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
Genome-wide meta-analyses of smoking behaviors in African Americans.
Content updated August 2026.
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