Treutlein Jens, Frank Josef, Streit Fabian, Reinbold Céline S, Juraeva Dilafruz, Degenhardt Franziska, Rietschel Liz, Witt Stephanie H, Forstner Andreas J, Ridinger Monika, Strohmaier Jana, Wodarz Norbert, Dukal Helene, Foo Jerome C, Hoffmann Per, Herms Stefan, Heilmann-Heimbach Stefanie, Soyka Michael, Maier Wolfgang, Gaebel Wolfgang, Dahmen Norbert, Scherbaum Norbert, Müller-Myhsok Bertram, Lucae Susanne, Ising Marcus, Stickel Felix, Berg Thomas, Roggenbuck Ulla, Jöckel Karl-Heinz, Scholz Henrike, Zimmermann Ulrich S, Buch Stephan, Sommer Wolfgang H, Spanagel Rainer, Brors Benedikt, Cichon Sven, Mann Karl, Kiefer Falk, Hampe Jochen, Rosendahl Jonas, Nöthen Markus M, Rietschel Marcella
Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, 68159 Mannheim, Germany.
Human Genomics Research Group, Department of Biomedicine, University and University Hospital Basel, 4031 Basel, Switzerland.
Genes (Basel). 2017 Jul 17;8(7):183. doi: 10.3390/genes8070183.
The present study investigated the genetic contribution to alcohol dependence (AD) using genome-wide association data from three German samples. These comprised patients with: (i) AD; (ii) chronic alcoholic pancreatitis (ACP); and (iii) alcohol-related liver cirrhosis (ALC). Single marker, gene-based, and pathway analyses were conducted. A significant association was detected for the locus in a gene-based approach ( = 1.2 × 10; = 0.020). This was driven by the AD subsample. No association with was found in the combined ACP + ALC sample. On first inspection, this seems surprising, since is a robustly replicated risk gene for AD and may therefore be expected to be associated also with subgroups of AD patients. The negative finding in the ACP + ALC sample, however, may reflect genetic stratification as well as random fluctuation of allele frequencies in the cases and controls, demonstrating the importance of large samples in which the phenotype is well assessed.
本研究利用来自三个德国样本的全基因组关联数据，调查了酒精依赖（AD）的遗传贡献。这些样本包括患有以下疾病的患者：（i）酒精依赖；（ii）慢性酒精性胰腺炎（ACP）；以及（iii）酒精性肝硬化（ALC）。进行了单标记、基于基因和通路分析。在基于基因的方法中，检测到一个位点存在显著关联（= 1.2 × 10；= 0.020）。这是由酒精依赖亚样本驱动的。在ACP + ALC合并样本中未发现与的关联。乍一看，这似乎令人惊讶，因为是酒精依赖的一个经过充分验证的风险基因，因此可能也预期与酒精依赖患者亚组相关。然而，ACP + ALC样本中的阴性发现可能反映了遗传分层以及病例组和对照组中等位基因频率的随机波动，这表明了在对表型进行充分评估的大样本中的重要性。
