rs56113850

This is a intron variant variant in the CYP2A6 gene.

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GWAS Catalog Trait Associations (76)

Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.

nicotine metabolite ratio

Buchwald J et al. “Genome-wide association meta-analysis of nicotine metabolism and cigarette consumption measures in smokers of European descent.” Molecular Psychiatry 26(6):2212-2223 (2021)
Allele T
OR 0.68
p 6.0e-261
N 5,185
Meta-analysis
European
Patel YM et al. “Novel Association of Genetic Markers Affecting CYP2A6 Activity and Lung Cancer Risk.” Cancer Research 76(19):5768-5776 (2016)
Allele T
OR 0.36
p 1.0e-50
N 2,239
Large GWAS
multi-ancestry
Chenoweth MJ et al. “Analyses of nicotine metabolism biomarker genetics stratified by sex in African and European Americans.” Scientific Reports 11(1):19572 (2021)
Allele T
OR 0.67
p 7.0e-22
N 389
Small GWAS
European

alkaline phosphatase measurement

Loya H et al. “A scalable variational inference approach for increased mixed-model association power.” Nature Genetics 57(2):461-468 (2025)
Allele C
OR 0.04
p 6.0e-105
N 394,642
Large GWAS
European
Sakaue S et al. “A cross-population atlas of genetic associations for 220 human phenotypes.” Nature Genetics 53(10):1415-1424 (2021)
Allele C
OR 0.05
p 1.0e-89
N 463,178
Large GWAS
multi-ancestry

3-methylxanthine measurement

Surendran P et al. “Rare and common genetic determinants of metabolic individuality and their effects on human health.” Nature Medicine 28(11):2321-2332 (2022)
Allele T
OR 0.14
p 3.0e-44
N 14,296
Large GWAS
European
Hysi PG et al. “Metabolome Genome-Wide Association Study Identifies 74 Novel Genomic Regions Influencing Plasma Metabolites Levels.” Metabolites 12(1) (2022)
Allele T
OR 0.15
p 2.0e-24
N 8,809
Large GWAS
European
Yin X et al. “Genome-wide association studies of metabolites in Finnish men identify disease-relevant loci.” Nature Communications 13(1):1644 (2022)
Allele T
OR 0.16
p 9.0e-18
N 6,136
Large GWAS
European

lung cancer

Gorman BR et al. “Multi-ancestry GWAS meta-analyses of lung cancer reveal susceptibility loci and elucidate smoking-independent genetic risk.” Nature Communications 15(1):8629 (2024)
Allele T
OR 0.89
p 1.0e-43
N 223,372
Large GWAS
multi-ancestry

X-21286 measurement

Surendran P et al. “Rare and common genetic determinants of metabolic individuality and their effects on human health.” Nature Medicine 28(11):2321-2332 (2022)
Allele T
OR 0.13
p 7.0e-38
N 14,296
Large GWAS
European
Hysi PG et al. “Metabolome Genome-Wide Association Study Identifies 74 Novel Genomic Regions Influencing Plasma Metabolites Levels.” Metabolites 12(1) (2022)
Allele T
OR 0.10
p 8.0e-12
N 8,809
Large GWAS
European
Chen Y et al. “Genomic atlas of the plasma metabolome prioritizes metabolites implicated in human diseases.” Nature Genetics 55(1):44-53 (2023)
Allele T
OR 0.14
p 2.0e-19
N 8,231
Large GWAS
European

glycine measurement

Zoodsma M et al. “A genetic map of human metabolism across the allele frequency spectrum.” Nature Genetics 57(10):2445-2455 (2025)
Allele C
OR 0.02
p 1.0e-36
N 450,015
Large GWAS
multi-ancestry
Richardson TG et al. “Characterising metabolomic signatures of lipid-modifying therapies through drug target mendelian randomisation.” Plos Biology 20(2):e3001547 (2022)
Allele C
OR 0.02
p 3.0e-8
N 114,978
Large GWAS
European
Davyson E et al. “Metabolomic Investigation of Major Depressive Disorder Identifies a Potentially Causal Association With Polyunsaturated Fatty Acids.” Biological Psychiatry 94(8):630-639 (2023)
Allele C
OR 0.03
p 7.0e-10
N 88,258
Large GWAS
European

X-12216 measurement

Surendran P et al. “Rare and common genetic determinants of metabolic individuality and their effects on human health.” Nature Medicine 28(11):2321-2332 (2022)
Allele T
OR 0.13
p 7.0e-35
N 14,296
Large GWAS
European
Hysi PG et al. “Metabolome Genome-Wide Association Study Identifies 74 Novel Genomic Regions Influencing Plasma Metabolites Levels.” Metabolites 12(1) (2022)
Allele T
OR 0.14
p 4.0e-20
N 8,809
Large GWAS
European
Chen Y et al. “Genomic atlas of the plasma metabolome prioritizes metabolites implicated in human diseases.” Nature Genetics 55(1):44-53 (2023)
Allele T
OR 0.13
p 7.0e-18
N 8,181
Large GWAS
European
Yin X et al. “Genome-wide association studies of metabolites in Finnish men identify disease-relevant loci.” Nature Communications 13(1):1644 (2022)
Allele T
OR 0.15
p 3.0e-15
N 6,136
Large GWAS
European
Schlosser P et al. “Genetic studies of paired metabolomes reveal enzymatic and transport processes at the interface of plasma and urine.” Nature Genetics 55(6):995-1008 (2023)
Allele T
OR 0.17
p 8.0e-12
N 4,797
Large GWAS
European

X-21831 measurement

Schlosser P et al. “Genetic studies of paired metabolomes reveal enzymatic and transport processes at the interface of plasma and urine.” Nature Genetics 55(6):995-1008 (2023)
Allele C
OR 0.47
p 8.0e-31
N 4,599
Large GWAS
European

indolin-2-one measurement

Surendran P et al. “Rare and common genetic determinants of metabolic individuality and their effects on human health.” Nature Medicine 28(11):2321-2332 (2022)
Allele T
OR 0.14
p 1.0e-30
N 14,296
Large GWAS
European
Chen Y et al. “Genomic atlas of the plasma metabolome prioritizes metabolites implicated in human diseases.” Nature Genetics 55(1):44-53 (2023)
Allele T
OR 0.17
p 2.0e-24
N 7,027
Large GWAS
European
Yin X et al. “Genome-wide association studies of metabolites in Finnish men identify disease-relevant loci.” Nature Communications 13(1):1644 (2022)
Allele T
OR 0.17
p 7.0e-15
N 6,136
Large GWAS
European

X-18935 measurement

Schlosser P et al. “Genetic studies of paired metabolomes reveal enzymatic and transport processes at the interface of plasma and urine.” Nature Genetics 55(6):995-1008 (2023)
Allele C
OR 0.29
p 1.0e-29
N 4,893
Large GWAS
European
Chen Y et al. “Genomic atlas of the plasma metabolome prioritizes metabolites implicated in human diseases.” Nature Genetics 55(1):44-53 (2023)
Allele C
OR 0.13
p 8.0e-11
N 4,952
Large GWAS
European
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Research that mentions this SNP (1)

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Dissecting the genetic overlap of smoking behaviors, lung cancer, and chronic obstructive pulmonary disease: A focus on nicotinic receptors and nicotine metabolizing enzyme
Meta-analysisN=1,200,000Michael J. Bray et al.(2020)· Genetic Epidemiology

This meta-analysis using GWAS summary statistics examined genetic correlations between smoking behaviors (cigarettes smoked per day, smoking cessation), lung cancer, and COPD. Strong positive genetic correlations were found between heavier smoking, reduced smoking cessation, and increased lung cancer and COPD risk. Notably, rs56113850 in CYP2A6 (effect allele C) showed a paradoxical pattern: associated with heavier smoking (z=19.2, p=1.10×10⁻⁸¹) and lung cancer (z=8.91, p=5.02×10⁻¹⁹) yet also with increased smoking cessation (z=-8.17, p=2.52×10⁻²⁶), highlighting the complex relationship between nicotine metabolism and smoking behaviors.

Traits studied:Chronic obstructive pulmonary disease (COPD)Cigarettes smoked per dayLung cancerSmoking cessation
PubMedDOIMetascience Observatory

About CYP2A6

This gene, CYP2A6, encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum and its expression is induced by phenobarbital. The enzyme is known to hydroxylate coumarin, and also metabolizes nicotine, aflatoxin B1, nitrosamines, and some pharmaceuticals. Individuals with certain allelic variants are said to have a poor metabolizer phenotype, meaning they do not efficiently metabolize coumarin or nicotine. This gene is part of a large cluster of cytochrome P450 genes from the CYP2A, CYP2B and CYP2F subfamilies on chromosome 19q. The gene was formerly referred to as CYP2A3; however, it has been renamed CYP2A6. [provided by RefSeq, Jul 2008]

View all CYP2A6 variants →

Gene information from NCBI Gene. Variant classifications from ClinVar.

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