Kruger S D, Turner W J, Kidd K K
Biol Psychiatry. 1982 Oct;17(10):1081-99.
Two large pedigrees with a bipolar proband were selected on the basis of compatibility with the hypothesis of autosomal dominant inheritance of a depressive taxon. We compared the results of linkage analyses of the depressive taxon with HLA and GLO in these pedigrees when penetrance function, diagnostic classification, and HLA haplotype frequencies were varied. The analyses show that all three types of assumptions affect the lod scores and likelihoods obtained. Using the most favorable assumptions, we obtain a lod score of 3.901 at theta = 0.10 for HLA with the depressive taxon. This lod score would conventionally be considered strong evidence of linkage of a subtype of manic-depressive illness with HLA but the dependence of these results on several untested assumptions suggests more cautious interpretation. Nonetheless, we feel it does represent evidence in favor of linkage because this high a lod score cannot readily be dismissed as statistical artifact. The results point out the importance of careful delineation of the assumptions made in linkage analyses of complex disorders, including the diagnostic criteria, marker allele frequencies, and age-of-onset function used.
基于与抑郁分类群常染色体显性遗传假说的相容性，选择了两个以双相情感障碍先证者为起点的大型家系。当外显率函数、诊断分类和HLA单倍型频率发生变化时，我们比较了这些家系中抑郁分类群与HLA和GLO的连锁分析结果。分析表明，所有三种类型的假设都会影响获得的lod分数和似然性。使用最有利的假设，我们在θ = 0.10时，针对抑郁分类群与HLA获得了3.901的lod分数。按照惯例，这个lod分数会被视为躁郁症亚型与HLA连锁的有力证据，但这些结果对几个未经检验的假设的依赖性表明需要更谨慎的解释。尽管如此，我们认为它确实代表了支持连锁的证据，因为这么高的lod分数不太可能轻易被视为统计假象。结果指出了在复杂疾病的连锁分析中仔细描述所做假设的重要性，包括诊断标准、标记等位基因频率和使用的发病年龄函数。
