Genome-wide association study of alcohol dependence.
Genome-wide association study of alcohol dependence.
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DOI：
10.1001/archgenpsychiatry.2009.83
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发表时间：
2009-07
影响因子：
--
通讯作者：
Rietschel, Marcella
中科院分区：
文献类型：
--
作者：
Treutlein, Jens;Cichon, Sven;Ridinger, Monika;Wodarz, Norbert;Soyka, Michael;Zill, Peter;Maier, Wolfgang;Moessner, Rainald;Gaebel, Wolfgang;Dahmen, Norbert;Fehr, Christoph;Scherbaum, Norbert;Steffens, Michael;Ludwig, Kerstin U.;Frank, Josef;Wichmann, H. Erich;Schreiber, Stefan;Dragano, Nico;Sommer, Wolfgang H.;Leonardi-Essmann, Fernando;Lourdusamy, Anbarasu;Gebicke-Haerter, Peter;Wienker, Thomas F.;Sullivan, Patrick F.;Noethen, Markus M.;Kiefer, Falk;Spanagel, Rainer;Mann, Karl;Rietschel, Marcella
识别导致酒精依赖的基因将提高我们对这种疾病背后的机制的理解。通过对发病年龄较早的德国男性住院患者进行全基因组关联研究和随访研究，确定酒精依赖的易感基因。GWAS包括487名发病年龄在28岁以下的DSM-IV酒精依赖住院男性患者和1358名以人群为基础的对照组个人。随访研究包括1024名男性住院患者和996名年龄匹配的男性对照组。所有受试者都有德国血统。Gwas检测了524,396个单核苷酸多态(SNPs)。对所有携带p<；10-4的SNPs进行随访研究。此外，来自那些在长期饮酒后大鼠大脑中也显示出表达变化的基因的名义上有意义的SNPs被选为后续步骤。GWAs生产了121个SNPs，名义p<；10-4。在后续的样本中，这些基因与另外19个来自大鼠基因同源物的差异表达的SNPs被进行了基因分型。15个SNPs的等位基因与GWA群的等位基因显著相关。在联合分析中，两个紧密连锁的基因间SNPs符合全基因组意义(rs7590720 p=9.72×10-9；rs1344694 p=1.69×10-8)。它们位于染色体2q35上，这一区域与酒精表型的连锁研究有关。9个SNP位于基因中，包括CDH13和ADH1C基因，这两个基因已被报道与酒精依赖有关。这是第一个确定全基因组范围内与酒精依赖有显著关联的GWAS和后续研究。需要进一步的独立研究来证实这些发现。
Identification of genes contributing to alcohol dependence will improve our understanding of the mechanisms underlying this disorder. To identify susceptibility genes for alcohol dependence through a genome-wide association study (GWAS) and follow-up study in a population of German male inpatients with an early age at onset. The GWAS included 487 male inpatients with DSM-IV alcohol dependence with an age at onset below 28 years and 1,358 population based control individuals. The follow-up study included 1,024 male inpatients and 996 age-matched male controls. All subjects were of German descent. The GWAS tested 524,396 single nucleotide polymorphisms (SNPs). All SNPs with p<10-4 were subjected to the follow-up study. In addition, nominally significant SNPs from those genes that had also shown expression changes in rat brains after chronic alcohol consumption were selected for the follow-up step. The GWAS produced 121 SNPs with nominal p<10-4. These, together with 19 additional SNPs from homologs of rat genes showing differential expression, were genotyped in the follow-up sample. Fifteen SNPs showed significant association with the same allele as in the GWAS. In the combined analysis, two closely linked intergenic SNPs met genome-wide significance (rs7590720 p=9.72×10-9; rs1344694 p=1.69×10-8). They are located on chromosome 2q35, a region which has been implicated in linkage studies for alcohol phenotypes. Nine SNPs were located in genes, including CDH13 and ADH1C genes which have been reported to be associated with alcohol dependence. This is the first GWAS and follow-up study to identify a genome-wide significant association in alcohol dependence. Further independent studies are required to confirm these findings.
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影响因子：
56.9
作者：
CLONINGER, CR
通讯作者：
CLONINGER, CR
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
30.8
作者：
Buch, Stephan;Schafmayer, Clemens;Hampe, Jochen
通讯作者：
Hampe, Jochen
影响因子：
0.9
作者：
Benegal, V;Jain, S;Channabasavanna, SM
通讯作者：
Channabasavanna, SM
影响因子：
6.7
作者：
Dick, Danielle M;Bierut, Laura J
通讯作者：
Bierut, Laura J