| Title |
A Novel, Functional and Replicable Risk Gene Region for Alcohol Dependence Identified by Genome-Wide Association Study
|
|---|---|
| Published in |
PLOS ONE, November 2011
|
| DOI | 10.1371/journal.pone.0026726 |
| Pubmed ID | |
| Authors |
Lingjun Zuo, Clarence K. Zhang, Fei Wang, Chiang-Shan R. Li, Hongyu Zhao, Lingeng Lu, Xiang-Yang Zhang, Lin Lu, Heping Zhang, Fengyu Zhang, John H. Krystal, Xingguang Luo |
| Abstract |
Several genome-wide association studies (GWASs) reported tens of risk genes for alcohol dependence, but most of them have not been replicated or confirmed by functional studies. The present study used a GWAS to search for novel, functional and replicable risk gene regions for alcohol dependence. Associations of all top-ranked SNPs identified in a discovery sample of 681 African-American (AA) cases with alcohol dependence and 508 AA controls were retested in a primary replication sample of 1,409 European-American (EA) cases and 1,518 EA controls. The replicable associations were then subjected to secondary replication in a sample of 6,438 Australian family subjects. A functional expression quantitative trait locus (eQTL) analysis of these replicable risk SNPs was followed-up in order to explore their cis-acting regulatory effects on gene expression. We found that within a 90 Mb region around PHF3-PTP4A1 locus in AAs, a linkage disequilibrium (LD) block in PHF3-PTP4A1 formed the only peak associated with alcohol dependence at p<10(-4). Within this block, 30 SNPs associated with alcohol dependence in AAs (1.6×10(-5)≤p≤0.050) were replicated in EAs (1.3×10(-3)≤p≤0.038), and 18 of them were also replicated in Australians (1.8×10(-3)≤p≤0.048). Most of these risk SNPs had strong cis-acting regulatory effects on PHF3-PTP4A1 mRNA expression across three HapMap samples. The distributions of -log(p) values for association and functional signals throughout this LD block were highly consistent across AAs, EAs, Australians and three HapMap samples. We conclude that the PHF3-PTP4A1 region appears to harbor a causal locus for alcohol dependence, and proteins encoded by PHF3 and/or PTP4A1 might play a functional role in the disorder. |
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 3 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Scientists | 2 | 67% |
| Members of the public | 1 | 33% |
Mendeley readers
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 40 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 11 | 28% |
| Student > Ph. D. Student | 6 | 15% |
| Student > Doctoral Student | 5 | 13% |
| Student > Bachelor | 2 | 5% |
| Professor | 2 | 5% |
| Other | 6 | 15% |
| Unknown | 8 | 20% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 9 | 23% |
| Neuroscience | 5 | 13% |
| Medicine and Dentistry | 4 | 10% |
| Psychology | 3 | 8% |
| Nursing and Health Professions | 2 | 5% |
| Other | 6 | 15% |
| Unknown | 11 | 28% |