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Genome-wide meta-analyses identify multiple loci associated with smoking behavior.

Publication ,  Journal Article
Tobacco and Genetics Consortium,
Published in: Nat Genet
May 2010

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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Published In

Nat Genet

DOI

EISSN

1546-1718

Publication Date

May 2010

Volume

42

Issue

5

Start / End Page

441 / 447

Location

United States

Related Subject Headings

  • Smoking
  • Receptors, Nicotinic
  • Polymorphism, Single Nucleotide
  • Phenotype
  • Odds Ratio
  • Molecular Epidemiology
  • Male
  • Humans
  • Genotype
  • Genome-Wide Association Study
 

Citation

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Tobacco and Genetics Consortium, . (2010). Genome-wide meta-analyses identify multiple loci associated with smoking behavior. Nat Genet, 42(5), 441–447. https://doi.org/10.1038/ng.571
Tobacco and Genetics Consortium, Thomas L. “Genome-wide meta-analyses identify multiple loci associated with smoking behavior.Nat Genet 42, no. 5 (May 2010): 441–47. https://doi.org/10.1038/ng.571.
Tobacco and Genetics Consortium. Genome-wide meta-analyses identify multiple loci associated with smoking behavior. Nat Genet. 2010 May;42(5):441–7.
Tobacco and Genetics Consortium, Thomas L. “Genome-wide meta-analyses identify multiple loci associated with smoking behavior.Nat Genet, vol. 42, no. 5, May 2010, pp. 441–47. Pubmed, doi:10.1038/ng.571.
Tobacco and Genetics Consortium. Genome-wide meta-analyses identify multiple loci associated with smoking behavior. Nat Genet. 2010 May;42(5):441–447.

Published In

Nat Genet

DOI

EISSN

1546-1718

Publication Date

May 2010

Volume

42

Issue

5

Start / End Page

441 / 447

Location

United States

Related Subject Headings

  • Smoking
  • Receptors, Nicotinic
  • Polymorphism, Single Nucleotide
  • Phenotype
  • Odds Ratio
  • Molecular Epidemiology
  • Male
  • Humans
  • Genotype
  • Genome-Wide Association Study