Genetic predisposition to organ-specific endpoints of alcoholism
Genetic predisposition to organ-specific endpoints of alcoholism
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DOI：
10.1111/j.1530-0277.1996.tb01695.x
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发表时间：
1996-12-01
影响因子：
3.2
通讯作者：
Christian, JC
中科院分区：
文献类型：
--
作者：
Reed, T;Page, WF;Christian, JC
美国国家科学院-国家研究理事会（NAS-NRC）双胞胎登记处的15,924对双胞胎的医疗记录被收集了16年，直到1994年，当时存活的双胞胎年龄在67岁到77岁之间。与早期的分析相比（Hrubec，Z.，Omenn，G.美国，酒精临床有效期Res，5：207-215，1981），当受试者年龄在51至61岁时，酒精中毒的诊断增加了23%（34.4/1000患病率），酒精性精神病的诊断增加了32%（5.4/1000），双胞胎肝硬化增加了25%（17.7/1000）。总体而言，5.3%的队列至少有一项与酗酒有关的诊断。Probandwise一致率（%）为：酒精中毒-26.7单合子（MZ），12.2双合子（DZ）（p < 0.0001）;酒精性精神病-17.3 MZ，4.8 DZ（p < 0.05）;肝硬化-16.9 MZ，5.3 DZ（p < 0.001）。与酒精中毒相关的任何诊断的一致性为30.2 MZ，13.9 DZ（p < 0.0001）。最大似然模型表明，类似的50%的整体方差是由于加性遗传效应，在所有的诊断类别，一个完全的环境模型给了一个显着较差的数据拟合。二变量和三变量遗传分析表明，精神病和肝硬化的器官特异性终点的大部分遗传易感性是由于酗酒的共同遗传易感性。一旦考虑到与酒精中毒的共同变异，就没有进一步的共同遗传易感性精神病和肝硬化。我们的研究结果证实了Hrubec和Omenn的结论，即NAS-NRC双胞胎中MZ双胞胎对酒精性精神病和肝硬化的一致性显著更高，一致率与16年前报道的一致率相似。相比之下，我们发现酒精中毒的器官特异性并发症的遗传易感性与酒精中毒本身的遗传易感性是共同的;只有一小部分个体并发症的遗传变异与酒精中毒的遗传易感性无关。
Medical records of the 15,924 twin-pairs in the National Academy of Sciences-National Research Council (NAS-NRC) twin registry were collected for an additional 16 years through 1994 when the surviving twins were aged 67 to 77 years. Compared with earlier analyses (Hrubec, Z., and Omenn, G. S., Alcohol. Clin. Exp. Res, 5:207-215, 1981), when subjects were aged 51 to 61, there were 23% more diagnoses of alcoholism (34.4 per 1,000 prevalence), 32% more diagnoses of alcoholic psychosis (5.4 per 1,000), and 25% more twins with liver cirrhosis (17.7 per 1,000). Overall, 5.3% of the cohort had at least one of the diagnoses related to alcoholism. Probandwise concordance rates (%) were: alcoholism-26.7 monozygotic (MZ), 12.2 dizygotic (DZ) (p < 0.0001); alcoholic psychosis-17.3 MZ, 4.8 DZ (p < 0.05); and cirrhosis-16.9 MZ, 5.3 DZ (p < 0.001). Concordance for any diagnosis related to alcoholism was 30.2 MZ, 13.9 DZ (p < 0.0001). Maximum-likelihood modeling indicated that similar to 50% of the overall variance was due to additive genetic effects; in all diagnosis categories, a totally environmental model gave a significantly poorer fit to the data. Bivariate and trivariate genetic analyses indicated most of the genetic liability for the organ-specific endpoints of psychosis and cirrhosis was due to the shared genetic liability for alcoholism. Once the shared variance with alcoholism was considered, there was no further shared genetic liability for psychosis and cirrhosis. Our results confirm Hrubec and Omenn's conclusion that there was significantly greater concordance in MZ twins-pairs for alcoholic psychosis and cirrhosis in the NAS-NRC twins, and concordance rates remained similar to those reported 16 years earlier. In contrast, we found most of the genetic liability to organ-specific complications of alcoholism was shared with the genetic liability for alcoholism per se; only a small portion of the genetic variance of the individual complications was independent of the genetic predisposition for alcoholism.