Kidd K K, Matthysee S
Arch Gen Psychiatry. 1978 Aug;35(8):925-32. doi: 10.1001/archpsyc.1978.01770320019001.
Understanding the genetic and environmental contributions (and their interactions, which are likely to be complex) to the etiology of psychiatric disorders requires research designs incorporating many basic principles of genetics. Genetic variation is likely to contribute to psychiatric disorders and genetic heterogeneity is likely to exist for any single disorder, ie, completely different genetic variants may each be capable of increasing an individual's susceptibility to the disorder. Thus, it is important to define phenotypes that may more closely reflect each individual genetic variant rather than to rely solely on the psychiatric diagnosis. Research should be undertaken with the goal of testing specific hypotheses that can be excluded. Research designs can include studies of unrelated individuals, twins, separated relatives, nuclear families, or extended pedigrees. Not all hypotheses can be tested on one type of data, and appropriate analytic methods vary. Because genetic hypotheses cannot be tested on studies of unrelated individuals, it is important that data be collected on families instead of unrelated individual patients and/or controls. Studies should include traits that bridge the gap between the genotype and the diagnostic phenotype. Such studies should be multidisciplinary, and the best statistical-genetics methodology should be used for data analysis.
要了解遗传和环境因素（以及它们之间可能很复杂的相互作用）对精神疾病病因的影响，需要采用包含许多遗传学基本原理的研究设计。遗传变异可能导致精神疾病，而且任何一种单一疾病都可能存在遗传异质性，也就是说，完全不同的基因变异可能各自都能增加个体患该疾病的易感性。因此，定义可能更紧密反映每个个体基因变异的表型很重要，而不是仅仅依赖于精神疾病诊断。开展研究应以检验可被排除的特定假设为目标。研究设计可以包括对无亲缘关系个体、双胞胎、分开抚养的亲属、核心家庭或扩展家系的研究。并非所有假设都能在一种类型的数据上进行检验，而且合适的分析方法也各不相同。由于遗传假设不能在对无亲缘关系个体的研究中进行检验，所以收集家庭数据而非无亲缘关系个体患者和/或对照的数据很重要。研究应包括能弥合基因型和诊断表型之间差距的性状。此类研究应是多学科的，并且应使用最佳的统计遗传学方法进行数据分析。
