Pathway analysis of smoking quantity in multiple GWAS identifies cholinergic and sensory pathways.
paper
Primary
Public
- Authors
- Harari, Oscar; Wang, Jen-Chyong; Bucholz, Kathleen; Edenberg, Howard J; Heath, Andrew; Martin, Nicholas G; Pergadia, Michele L; Montgomery, Grant; Schrage, Andrew; Bierut, Laura J; Madden, Pamela F; Goate, Alison M
- Year
- 2012
- Journal
- PloS one
- PMID
- 23227220
- DOI
- 10.1371/journal.pone.0050913
- PMCID
- PMC3515482
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.
Go terms for cholinergic receptors and significant genes.The p-value of each gene was assigned based on the most significant SNP in gene sequences and flanking regions (Left panel). SNPs in linkage disequilibrium (r2>0.2) and in a local proximity (1 Mb) were removed. Colored boxes in the right panel reflect the assignment of each gene to the different GO terms.
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| The genetic epidemiology of substance use disorder: A review. | 2017 | 28938182 |
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