Craddock N, Khodel V, Van Eerdewegh P, Reich T
Department of Psychiatry, Washington University School of Medicine, St. Louis, USA.
Am J Hum Genet. 1995 Sep;57(3):690-702.
We describe a simple, graphical method for determining plausible modes of inheritance for complex traits and apply this to bipolar disorder. The constraints that allele frequencies and penetrances lie in the interval 0-1 impose limits on recurrence risks, KR, in relatives of an affected proband for a given population prevalence, KP. We have investigated these limits for KR in three classes of relatives (MZ co-twin, sibling, and parent/offspring) for the general single-locus model and for two types of multilocus models: heterogeneity and multiplicative. In our models we have assumed Hardy-Weinberg equilibrium, an all-or-none trait, absence of nongenetic resemblance between relatives, and negligible mutation at the disease loci. Although the true values of KP and the KR's are only approximately known, observed population and family data for bipolar disorder are inconsistent with a single-locus model or with any heterogeneity model. In contrast, multiplicative models involving three or more loci are consistent with observed data and, thus, represent plausible models for the inheritance of bipolar disorders. Studies to determine the genetic basis of most bipolar disorder should use methods capable of detecting interacting oligogenes.
我们描述了一种简单的图形方法，用于确定复杂性状可能的遗传模式，并将其应用于双相情感障碍。对于给定的人群患病率(KP)，等位基因频率和外显率处于(0 - 1)区间这一限制条件对患病先证者亲属的复发风险(KR)施加了限制。我们针对一般单基因座模型以及两种多基因座模型（异质性模型和乘积模型），研究了三类亲属（同卵双生子、同胞以及父母/子女）的(KR)限制。在我们的模型中，我们假设处于哈迪 - 温伯格平衡、性状为全或无、亲属间不存在非遗传相似性以及疾病基因座的突变可忽略不计。尽管(KP)和(KR)的真实值仅大致已知，但双相情感障碍的观察到的人群和家系数据与单基因座模型或任何异质性模型均不一致。相比之下，涉及三个或更多基因座的乘积模型与观察到的数据一致，因此代表了双相情感障碍遗传的合理模型。确定大多数双相情感障碍遗传基础的研究应使用能够检测相互作用的寡基因的方法。
