Pathway Analysis of Smoking Quantity in Multiple GWAS Identifies Cholinergic and Sensory Pathways
Year: 2012
Type: article
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.
Source: PLoS ONE
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,382
Funders: Foundation for Barnes-Jewish Hospital, National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism, National Heart, Lung, and Blood Institute, National Institute on Drug Abuse, National Human Genome Research Institute, National Cancer Institute, National Center for Research Resources
Awards: G1425089079, G1738478728, Institute for Clinical and Translational Research (UL1), G2561471519, Study of Addiction: Genetics and Environment, Molecular Epidemiology of Alcoholism 3 - EDAC Families, G3548961933, G3619332945, G363841575, G3799582765, RESEARCH EDUCATION PROGRAM ON COMPUTATIONAL AND STATISTICAL TOOL DEVELOPMENT FOR ADDICTION GENETICS, G4340265572, G536099884, JH/CIDR Genotyping for Genome-Wide Association Studies, FAMILY STUDY OF COCAINE DEPENDENCE, Refining Phenotypic Measures of Nicotine Withdrawal, Molecular Epidemiology of Alcoholism 2- Big Sibships, VARIATION IN THE EFFECTS OF ALCOHOL ON LIVER FUNCTION, G8278726054, G8471761114, PERSISTENCE AND CHANGE IN DRINKING HABITS--TWIN STUDY, G858805679, From GWAS loci to blood pressure genes, variants & mechanisms - Renewal, G902688188, G977574824, G983815670
OpenAlex ID: W2030312428