Reed T, Page W F, Viken R J, Christian J C
Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, USA.
Alcohol Clin Exp Res. 1996 Dec;20(9):1528-33. doi: 10.1111/j.1530-0277.1996.tb01695.x.
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 approximately 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.
美国国家科学院-国家研究委员会（NAS-NRC）双胞胎登记处的15924对双胞胎的医疗记录又收集了16年，直至1994年，那时存活的双胞胎年龄在67至77岁之间。与早期分析（Hrubec, Z, 和Omenn, G. S.，《酒精临床与实验研究》，5:207 - 215, 1981）相比，当时研究对象年龄在51至61岁，酗酒的诊断增加了23%（患病率为每1000人中有34.4例），酒精性精神病的诊断增加了32%（每1000人中有5.4例），患肝硬化的双胞胎增加了25%（每1000人中有17.7例）。总体而言，该队列中有5.3%的人至少有一项与酗酒相关的诊断。先证者一致率（%）为：酗酒——同卵双胞胎（MZ）为26.7，异卵双胞胎（DZ）为12.2（p < 0.0001）；酒精性精神病——MZ为17.3，DZ为4.8（p < 0.05）；肝硬化——MZ为16.9，DZ为5.3（p < 0.001）。任何与酗酒相关诊断的一致率为MZ为30.2，DZ为13.9（p < 0.0001）。最大似然模型表明，总体方差中约50%归因于加性遗传效应；在所有诊断类别中，完全环境模型对数据的拟合明显更差。双变量和三变量遗传分析表明，精神病和肝硬化器官特异性终点的大部分遗传易感性是由于与酗酒共享的遗传易感性。一旦考虑了与酗酒的共享方差，精神病和肝硬化之间就没有进一步的共享遗传易感性。我们的结果证实了Hrubec和Omenn的结论，即在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明显更高，且一致率与16年前报告的相似。相比之下，我们发现酗酒器官特异性并发症的大部分遗传易感性与酗酒本身的遗传易感性是共享的；个体并发症的遗传方差中只有一小部分独立于酗酒的遗传易感性。
