Genetic variability in the NMDA‐dependent AMPA trafficking cascade is associated with alcohol dependence
Year: 2011
Type: article
Abstract: Model studies in mice indicate that the severity of alcohol withdrawal is associated with polymorphic variation and expression of the MPDZ gene. Current knowledge about variation in the human MPDZ gene is limited; however, our data indicate its potential association with alcohol dependence. The multi-PDZ protein is an important part of the N-methyl-D-aspartate (NMDA)-dependent α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor trafficking cascade that controls glutamate-related excitatory neurotransmission. To investigate association of variation in the NMDA-dependent AMPA trafficking cascade with alcohol dependence, we performed a gene-set (pathway) analysis using single nucleotide polymorphism (SNP) data from the Study of Addiction: Genetic and Environment. Rather than testing for association with each SNP individually, which typically has low power to detect small effects of multiple SNPs, gene-set analysis applies a single statistical test to evaluate whether variation in a set of genes is associated with the phenotype of interest. Gene-set analysis of 988 SNPs in 13 genes in the pathway demonstrated a significant association with alcohol dependence, with P < 0.01 for the global effect of variation in this pathway. The statistically significant association of alcohol dependence with genetic variation in the NMDA-dependent AMPA receptor trafficking cascade indicates a need for further investigation of the role of this pathway in alcohol dependence.
Source: Addiction Biology
Institution: Mayo Clinic
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: bronze
Awards: Study of Addiction: Genetics and Environment, Pathway-based analysis of addiction susceptibility genes, The Collaborative Genetic Study of Nicotine Dependence, Genome Wide Association Coordinating Center, JH/CIDR Genotyping for Genome-Wide Association Studies, FAMILY STUDY OF COCAINE DEPENDENCE, G8267674335, Collaborative Study on the Genetics of Alcoholism (COGA).
OpenAlex ID: W2114059961