Genome-wide significant association between alcohol dependence and a variant in the ADH gene cluster.
Genome-wide significant association between alcohol dependence and a variant in the ADH gene cluster.
复制标题
酒精依赖性与ADH基因簇中的变体之间的全基因组显着关联。
DOI：
10.1111/j.1369-1600.2011.00395.x
复制
发表时间：
2012-01
影响因子：
3.4
通讯作者：
Rietschel M
中科院分区：
文献类型：
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作者：
Frank J;Cichon S;Treutlein J;Ridinger M;Mattheisen M;Hoffmann P;Herms S;Wodarz N;Soyka M;Zill P;Maier W;Mössner R;Gaebel W;Dahmen N;Scherbaum N;Schmäl C;Steffens M;Lucae S;Ising M;Müller-Myhsok B;Nöthen MM;Mann K;Kiefer F;Rietschel M
酒精依赖（AD）是全球疾病负担的一个重要因素。AD的病因涉及环境和遗传因素，并且该疾病的遗传率约为50%。本研究的目的是通过全基因组关联研究（GWAS）确定AD的易感基因。样本包括1，333名患有严重DSM-IV AD的男性住院患者和2，168名对照。其中包括487名患者和1,358名对照，来自我们小组先前的GWAS研究。所有人都是德国血统。进行单标记测试和基于多基因评分的分析，以评估具有小影响的多个标记的组合贡献。位于ADH1B和ADH1C基因之间的SNP rs1789891实现了全基因组显著性（p = 1.27E-8; OR = 1.46）。来自该地区的其他标志物也与AD相关，条件分析表明，这些标志物做出了部分独立的贡献。SNP rs1789891与ADH 1C基因的功能性Arg272Gln变体（p = 1.24E-7，OR = 1.31）处于完全连锁不平衡，据报道该变体在体外改变乙醇氧化为乙醛的速率。基于多基因评分的方法产生显著结果（p = 9.66E-9）。这是AD的第一个GWAS，为ADH基因簇的作用提供了全基因组的重要支持，并表明AD的病因学是多基因组成的。后者的结果表明，更多的AD易感基因仍有待鉴定。
Alcohol dependence (AD) is an important contributory factor to the global burden of disease. The etiology of AD involves both environmental and genetic factors, and the disorder has a heritability of around 50%. The aim of the present study was to identify susceptibility genes for AD by performing a genome-wide association study (GWAS). The sample comprised 1,333 male in-patients with severe DSM-IV AD and 2,168 controls. These included 487 patients and 1,358 controls from a previous GWAS study by our group. All individuals were of German descent. Single marker tests and a polygenic score based analysis to assess the combined contribution of multiple markers with small effects were performed. The SNP rs1789891, which is located between the ADH1B and ADH1C genes, achieved genome-wide significance (p=1.27E–8; OR=1.46). Other markers from this region were also associated with AD, and conditional analyses indicated that these made a partially independent contribution. The SNP rs1789891 is in complete linkage disequilibrium with the functional Arg272Gln variant (p=1.24E–7, OR=1.31) of the ADH1C gene, which has been reported to modify the rate of ethanol oxidation to acetaldehyde in vitro. A polygenic score based approach produced a significant result (p=9.66E–9). This is the first GWAS of AD to provide genome-wide significant support for the role of the ADH gene cluster and to suggest a polygenic component to the etiology of AD. The latter result suggests that many more AD susceptibility genes still await identification.
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影响因子：
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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
通讯作者：
Rietschel, Marcella
影响因子：
9.8
作者：
Osier, MV;Pakstis, AJ;Kidd, KK
通讯作者：
Kidd, KK
影响因子：
4.2
作者：
PICKENS, RW;SVIKIS, DS;LABUDA, MC
通讯作者：
LABUDA, MC
DOI：
10.1111/j.1530-0277.2010.01156.x
发表时间：
2010-05
期刊：
Alcoholism, clinical and experimental research
影响因子：
--
作者：
Edenberg HJ;Koller DL;Xuei X;Wetherill L;McClintick JN;Almasy L;Bierut LJ;Bucholz KK;Goate A;Aliev F;Dick D;Hesselbrock V;Hinrichs A;Kramer J;Kuperman S;Nurnberger JI Jr;Rice JP;Schuckit MA;Taylor R;Todd Webb B;Tischfield JA;Porjesz B;Foroud T
通讯作者：
Foroud T
影响因子：
10.6
作者：
Li, Dawei;Zhao, Hongyu;Gelernter, Joel
通讯作者：
Gelernter, Joel