Single-nucleotide polymorphisms in corticotropin releasing hormone receptor 1 gene (CRHR1) are associated with quantitative trait of event-related potential and alcohol dependence.
- Authors
- Chen, Andrew C H; Manz, Niklas; Tang, Yongqiang; Rangaswamy, Madhavi; Almasy, Laura; Kuperman, Samuel; Nurnberger, John; O'Connor, Sean J; Edenberg, Howard J; Schuckit, Marc A; Tischfield, Jay; Foroud, Tatiana; Bierut, Laura J; Rohrbaugh, John; Rice, John P; Goate, Alison; Hesselbrock, Victor; Porjesz, Bernice
- Year
- 2010
- Journal
- Alcoholism, clinical and experimental research
- PMID
- 20374216
- DOI
- 10.1111/j.1530-0277.2010.01173.x
- PMCID
- PMC3248053
BACKGROUND: Endophenotypes reflect more proximal effects of genes than diagnostic categories, hence providing a more powerful strategy in searching for genes involved in complex psychiatric disorders. There is strong evidence suggesting the P3 amplitude of the event-related potential (ERP) as an endophenotype for the risk of alcoholism and other disinhibitory disorders. Recent studies demonstrated a crucial role of corticotropin releasing hormone receptor 1 (CRHR1) in the environmental stress response and ethanol self-administration in animal models. The aim of the present study was to test the potential associations between single-nucleotide polymorphisms (SNPs) in the CRHR1 gene and the quantitative trait, P3 amplitude during the processing of visual target signals in an oddball paradigm, as well as alcohol dependence diagnosis. METHODS: We analyzed a sample from the Collaborative Study on the Genetics of Alcoholism (COGA) comprising 1049 Caucasian subjects from 209 families (including 472 alcohol-dependent individuals). Quantitative transmission disequilibrium test (QTDT) and family-based association test (FBAT) were used to test the association, and false discovery rate (FDR) was applied to correct for multiple comparisons. RESULTS: Significant associations (p < 0.05) were found between the P3 amplitude and alcohol dependence with multiple SNPs in the CRHR1 gene. CONCLUSIONS: Our results suggest that CRHR1 may be involved in modulating the P3 component of the ERP during information processing and in vulnerability to alcoholism. These findings underscore the utility of electrophysiology and the endophenotype approach in the genetic study of psychiatric disorders.
Pair-wise measures of linkage disequilibrium (LD) plot of the 9 CRHR1 SNPs based on subjects included in this study. The Lewontin’s standardized disequilibrium coefficient, D’, value of each SNP pair is shown in the squares. The numbers in the squares are D’ × 100. Empty squares indicate D’ = 1. Squares are colored bright red (dark gray) if the D’ value is high and the confidence in the value of D’ is high as well.
Mean target visual P3 amplitude at the seven posterior electrodes grouped by haplotypes. The bars represent the mean value; the vertical lines issuing from the bars represent the standard error of mean (SEM). Individual p-values are shown in Table 4.
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