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Public Library of Science, PLoS ONE, 12(7), p. e50913, 2012

DOI: 10.1371/journal.pone.0050913

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

Journal article published in 2012 by Oscar Harari, Jen-Chyong Wang, Kathleen Bucholz, Howard J. Edenberg ORCID, Andrew Heath, Nicholas G. Martin ORCID, Michele L. Pergadia, Grant Montgomery, Andrew Schrage, Laura J. Bierut, Pamela F. Madden, Alison M. Goate
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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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.