Smith C
Ann Hum Genet. 1976 Jan;39(3):281-91. doi: 10.1111/j.1469-1809.1976.tb00132.x.
If a disease can be split into two or more groups on any criterion (clinical, biochemical, physiological or statistical) then the grouping can be tested to establish if genetically independent forms of the disease have been identified. The data required are simply the frequencies of the two disease groups in relatives of probands for each of the disease groups. A systematic search for such distinct groups is proposed in searches for genetic heterogeneity in familial diseases. In disease forms with overlapping, correlated genetic liabilities, the method of Falconer (1967) can be used to estimate the genetic correlation. However, when the groupings of the disease are confounded (such as one form precluding the other as in early and late onset diabetes) Falconer's method will be biased. Special methods of analysis to estimate the genetic parameters have been developed and are presented here. However, even when the groupings are confounded the Falconer method still gives reasonable estimates of the genetic correlation, in that they are unlikely to seriously mislead the investigator in the analysis and interpretation of observed data. In practice Falconer's simple method may be preferred to the more complex methods developed here because it involves fewer assumptions and can be applied over a wider range of circumstances.
如果一种疾病可以根据任何标准（临床、生化、生理或统计学）分为两个或更多组，那么可以对分组进行检验，以确定是否识别出了该疾病的遗传独立形式。所需的数据仅仅是每个疾病组中先证者亲属的两种疾病组的频率。在寻找家族性疾病的遗传异质性时，建议对这种不同的组进行系统搜索。在具有重叠、相关遗传易感性的疾病形式中，可以使用Falconer（1967）的方法来估计遗传相关性。然而，当疾病的分组混淆时（例如，一种形式排除了另一种形式，如早发和晚发糖尿病），Falconer方法将产生偏差。本文开发并介绍了用于估计遗传参数的特殊分析方法。然而，即使分组混淆，Falconer方法仍然能给出合理的遗传相关性估计值，因为它们不太可能在观察数据的分析和解释中严重误导研究者。在实践中，Falconer的简单方法可能比这里开发的更复杂的方法更可取，因为它涉及的假设更少，并且可以在更广泛的情况下应用。
