Baron M
Acta Psychiatr Scand. 1981 Nov;64(5):431-41. doi: 10.1111/j.1600-0447.1981.tb00802.x.
The extent of genetic heterogeneity in major affective illness was estimated via three paradigms of single-major-locus inheritance. In the first paradigm bipolar and unipolar disorders were represented at different liability thresholds on a genetic-environmental continuum. The second paradigm incorporated sex-related thresholds into the model, thereby testing the hypothesis that affective illness is a transmitted trait whose phenotypic expression is a function of the individual's sex. The third paradigm included both clinical polarity and sex effect as threshold phenomena. All three paradigms predicted considerable genetic heterogeneity in affective disorders. Bipolar homozygotes were far more common than unipolar homozygotes, although the majority of ill individuals in the first two paradigms were heterozygotes. According to the third paradigm bipolar males had the highest proportion of homozygotes amongst the affected population. Significant increases in homozygosity occurred using the dual mating sampling method. Depending on the model paradigm and parameters these increases were 140-25,000% over the random sample method. The implications for biologic and genetic research in affective disorders were discussed.
通过单一位点遗传的三种模式，对主要情感障碍中的基因异质性程度进行了估计。在第一种模式中，双相情感障碍和单相情感障碍在遗传-环境连续统上处于不同的易感性阈值。第二种模式将与性别相关的阈值纳入模型，从而检验情感障碍是一种遗传性状，其表型表达是个体性别的函数这一假设。第三种模式将临床极性和性别效应都视为阈值现象。所有这三种模式都预测情感障碍中存在相当大的基因异质性。双相情感障碍纯合子比单相情感障碍纯合子更为常见，尽管在前两种模式中，大多数患病个体是杂合子。根据第三种模式，双相情感障碍男性在受影响人群中纯合子比例最高。使用双重交配抽样方法时，纯合性显著增加。根据模型模式和参数，这些增加幅度比随机抽样方法高出140%至25000%。文中讨论了这些结果对情感障碍生物学和遗传学研究的意义。
