{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T12:25:51Z","timestamp":1785932751723,"version":"3.56.0"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>It is believed that multiple genetic variants with small individual effects contribute to the risk of alcohol dependence. Such polygenic effects are difficult to detect in genome-wide association studies that test for association of the phenotype with each single nucleotide polymorphism (SNP) individually. To overcome this challenge, gene-set analysis (GSA) methods that jointly test for the effects of pre-defined groups of genes have been proposed. Rather than testing for association between the phenotype and individual SNPs, these analyses evaluate the global evidence of association with a set of related genes enabling the identification of cellular or molecular pathways or biological processes that play a role in development of the disease. It is hoped that by aggregating the evidence of association for all available SNPs in a group of related genes, these approaches will have enhanced power to detect genetic associations with complex traits. We performed GSA using data from a genome-wide study of 1165 alcohol-dependent cases and 1379 controls from the Study of Addiction: Genetics and Environment (SAGE), for all 200 pathways listed in the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Results demonstrated a potential role of the \u2018synthesis and degradation of ketone bodies\u2019 pathway. Our results also support the potential involvement of the \u2018neuroactive ligand\u2013receptor interaction\u2019 pathway, which has previously been implicated in addictive disorders. These findings demonstrate the utility of GSA in the study of complex disease, and suggest specific directions for further research into the genetic architecture of alcohol dependence.<\/jats:p>","DOI":"10.1017\/s1461145712000375","type":"journal-article","created":{"date-parts":[[2012,5,2]],"date-time":"2012-05-02T10:24:12Z","timestamp":1335954252000},"page":"271-278","source":"Crossref","is-referenced-by-count":37,"title":["Genome-wide gene-set analysis for identification of pathways associated with alcohol dependence"],"prefix":"10.1093","volume":"16","author":[{"given":"Joanna M.","family":"Biernacka","sequence":"first","affiliation":[{"name":"Divisions of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA"},{"name":"Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, 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