Gene-Based and Pathway-Based Genome-Wide Association Study of Alcohol Dependence
Document Type
Article
Publication Date
4-1-2015
Description
Background: The organization of risk genes within signaling pathways may provide clues about the converging neurobiological effects of risk genes for alcohol dependence. Aims: Identify risk genes and risk gene pathways for alcohol dependence. Methods: We conducted a pathway-based genome-wide association study (GWAS) of alcohol dependence using a gene-set-rich analytic approach. Approximately one million genetic markers were tested in the discovery sample which included 1409 European-American (EA) alcohol dependent individuals and 1518 EA healthy comparison subjects. An additional 681 African-American (AA) cases and 508 AA healthy subjects served as the replication sample. Results: We identified several genome-wide replicable risk genes and risk pathways that were significantly associated with alcohol dependence. After applying the Bonferroni correction for multiple testing, the 'cellextracellular matrix interactions' pathway (p<2.0E-4 in EAs) and the PXN gene (which encodes paxillin) (p=3.9E-7 in EAs) within this pathway were the most promising risk factors for alcohol dependence. There were also two nominally replicable pathways enriched in alcohol dependence-related genes in both EAs (0.015≤p≤0.035) and AAs (0.025≤p≤0.050): the 'Na+/Cl- dependent neurotransmitter transporters' pathway and the 'other glycan degradation' pathway. Conclusions: These findings provide new evidence highlighting several genes and biological signaling processes that may be related to the risk for alcohol dependence.
Citation Information
Zuo, Lingjun; Zhang, Clarence K.; Sayward, Frederick G.; Cheung, Kei Hoi; Wang, Kesheng; Krystal, John H.; Zhao, Hongyu; and Luo, Xingguang. 2015. Gene-Based and Pathway-Based Genome-Wide Association Study of Alcohol Dependence. Shanghai Archives of Psychiatry. Vol.27(2). 111-118. https://doi.org/10.11919/j.issn.1002-0829.215031 ISSN: 1002-0829