Genome-wide meta-analyses identify multiple loci associated with smoking behavior
Open accessAbstract
Consistent but indirect evidence has implicated genetic factors in smoking behavior. We report meta-analyses of several smoking phenotypes within cohorts of the Tobacco and Genetics Consortium (n = 74,053). We also partnered with the European Network of Genetic and Genomic Epidemiology (ENGAGE) and Oxford-GlaxoSmithKline (Ox-GSK) consortia to follow up the 15 most significant regions (n > 140,000). We identified three loci associated with number of cigarettes smoked per day. The strongest association was a synonymous 15q25 SNP in the nicotinic receptor gene CHRNA3 (rs1051730[A], beta = 1.03, standard error (s.e.) = 0.053, P = 2.8 x 10(-73)). Two 10q25 SNPs (rs1329650[G], beta = 0.367, s.e. = 0.059, P = 5.7 x 10(-10); and rs1028936[A], beta = 0.446, s.e. = 0.074, P = 1.3 x 10(-9)) and one 9q13 SNP in EGLN2 (rs3733829[G], beta = 0.333, s.e. = 0.058, P = 1.0 x 10(-8)) also exceeded genome-wide significance for cigarettes per day. For smoking initiation, eight SNPs exceeded genome-wide significance, with the strongest association at a nonsynonymous SNP in BDNF on chromosome 11 (rs6265[C], odds ratio (OR) = 1.06, 95% confidence interval (Cl) 1.04-1.08, P = 1.8 x 10(-8)). One SNP located near DBH on chromosome 9 (rs3025343[G], OR = 1.12, 95% Cl 1.08-1.18, P = 3.6 x 10(-8)) was significantly associated with smoking cessation.
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Gene discovery for tobacco and alcohol use has been difficult.
“They are heritable2,3 and etiologically related4,5 behaviors that have been resistant to gene discovery efforts6–11.”
From Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use (2019) · cites this paper as [9]
Multiple associations were found between CigDay and SmkCes with DBH (p=9.8×10−24 and 1.2×10−35, respectively).
“including multiple associations between CigDay and SmkCes with dopamine beta-hydroxylase (DBH, p=9.8×10−24 and 1.2×10−35, respectively)9”
From Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use (2019) · cites this paper as [9]
For ALC, the published GWAS are small and no large-scale meta-analysis has been conducted.
“For ALC, the published GWAS are small and no large-scale meta-analysis has been conducted. 93–97”
From Genetic architectures of psychiatric disorders: the emerging picture and its implications (2012) · cites this paper as [93]
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- Authors
- The Tobacco and Genetics Consortium
- Venue
- Nature Genetics
- Published
- 2010-04-25
- Volume
- 42
- Issue
- 5
- Pages
- 441-447
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- PMC
- PMC2914600
- OpenAlex
- W2110846909
- Cited by
- 1,098
- References
- 43
- Citations by year
- 2026: 10 · 2025: 16 · 2024: 21 · 2023: 38 · 2022: 38 · 2021: 79 · 2020: 102 · 2019: 89 · 2018: 107 · 2017: 97 · 2016: 95 · 2015: 82 · 2014: 77 · 2013: 73 · 2012: 84
- FWCI
- 52.62
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- VU Research Portal (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
- Digital Academic REpository of VU University Amsterdam (Vrije Universiteit Amsterdam) (submittedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- RePub (Erasmus University Rotterdam) (submittedVersion)
- STM:n Hallinnonalan avoin julkaisuarkisto (Julkari) (submittedVersion)
- Lenus, The Irish Health Repository (Dr Steevens Hospital Library) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Newcastle University ePrints (Newcastle Univesity)
- Funders
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (480- 05-003)
- National Institute on Drug Abuse (R01DA012844)
- National Cancer Institute (R01CA082659, K07CA118412)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK072193)
- Topics
- Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
- Keywords
- smoking behavior, genetic loci, cigarettes per day, smoking initiation, smoking cessation, CHRNA3, nicotinic acetylcholine receptors, brain-derived neurotrophic factor, DBH, EGLN2, nicotine dependence
- MeSH terms
- Age Factors, Alleles, Chromosome Mapping, Female, Genotype, Humans, Male, Phenotype, Receptors, Nicotinic, Smoking, Odds Ratio, Genome, Molecular Epidemiology, Polymorphism, Single Nucleotide, Genome-Wide Association Study
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