Pathway Analysis of Smoking Quantity in Multiple GWAS Identifies Cholinergic and Sensory Pathways

Oscar Harari, Jen Chyong Wang, Kathleen Bucholz, Howard J. Edenberg, Andrew Heath, Nicholas G. Martin, Michele L. Pergadia, Grant Montgomery, Andrew Schrage, Laura J. Bierut, Pamela F. Madden, Alison M. Goate

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Cigarette smoking is a common addiction that increases the risk for many diseases, including lung cancer and chronic obstructive pulmonary disease. Genome-wide association studies (GWAS) have successfully identified and validated several susceptibility loci for nicotine consumption and dependence. However, the trait variance explained by these genes is only a small fraction of the estimated genetic risk. Pathway analysis complements single marker methods by including biological knowledge into the evaluation of GWAS, under the assumption that causal variants lie in functionally related genes, enabling the evaluation of a broad range of signals. Our approach to the identification of pathways enriched for multiple genes associated with smoking quantity includes the analysis of two studies and the replication of common findings in a third dataset. This study identified pathways for the cholinergic receptors, which included SNPs known to be genome-wide significant; as well as novel pathways, such as genes involved in the sensory perception of smell, that do not contain any single SNP that achieves that stringent threshold.

Original languageEnglish (US)
Article numbere50913
JournalPloS one
Volume7
Issue number12
DOIs
StatePublished - Dec 5 2012

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Fingerprint Dive into the research topics of 'Pathway Analysis of Smoking Quantity in Multiple GWAS Identifies Cholinergic and Sensory Pathways'. Together they form a unique fingerprint.

  • Cite this

    Harari, O., Wang, J. C., Bucholz, K., Edenberg, H. J., Heath, A., Martin, N. G., Pergadia, M. L., Montgomery, G., Schrage, A., Bierut, L. J., Madden, P. F., & Goate, A. M. (2012). Pathway Analysis of Smoking Quantity in Multiple GWAS Identifies Cholinergic and Sensory Pathways. PloS one, 7(12), [e50913]. https://doi.org/10.1371/journal.pone.0050913