Lin M W, Sham P, Hwu H G, Collier D, Murray R, Powell J F
Department of Psychological Medicine and Neuroscience, Institute of Psychiatry, London, UK.
Hum Genet. 1997 Mar;99(3):417-20. doi: 10.1007/s004390050382.
Previously we reported suggestive evidence for linkage of schizophrenia to markers on chromosome 13q14.1-q32. We have now studied an additional independent sample of 44 pedigrees consisting of 34 Taiwanese, 9 English and 1 Welsh family in an attempt to replicate this finding. Narrow and broad models based on Research Diagnostic Criteria or the Diagnostic and Statistical Manual of Mental Disorders, third edition, revised, were used to define the schizophrenia phenotype. Under a dominant genetic model, two-point lod scores obtained for most of the markers were negative except that marker D13S122 gave a total lod score of 1.06 (theta = 0.2, broad model). As combining pedigrees from different ethnic origins may be inappropriate, we combined this replication sample and our original sample, and then divided the total sample into Caucasian (English and Welsh pedigrees) and Oriental (Taiwanese and Japanese pedigrees) groups. The Caucasian pedigrees produced maximized admixture two-point lod scores (A-lod) of 1.41 for the marker D13S119 (theta = 0.2, alpha = 1.0) and 1.54 for D13S128 (theta = 0, alpha = 0.3) with nearby markers also producing positive A-lod scores. When five-point model-free linkage analysis was applied to the Caucasian sample, a maximum lod score of 2.58 was obtained around the markers D13S122 and D13S128, which are located on chromosome 13q32. The linkage results for the Oriental group were less positive than the Caucasian group. Our results again suggest that there is a potential susceptibility locus for schizophrenia on chromosome 13q14.1-q32, especially in the Caucasian population.
此前我们报道了精神分裂症与13号染色体q14.1 - q32区域标记连锁的提示性证据。我们现在研究了另外一个由44个家系组成的独立样本，其中包括34个台湾家系、9个英国家系和1个威尔士家系，试图重复这一发现。基于研究诊断标准或《精神疾病诊断与统计手册》第三版修订本，采用狭义和广义模型来定义精神分裂症表型。在显性遗传模型下，除标记D13S122的总lod分数为1.06（θ = 0.2，广义模型）外，大多数标记获得的两点lod分数均为阴性。由于合并来自不同种族起源的家系可能不合适，我们将这个重复样本和我们原来的样本合并，然后将总样本分为白种人（英国家系和威尔士家系）和东方人（台湾家系和日本家系）两组。对于标记D13S119，白种人家系产生的最大混合两点lod分数（A - lod）为1.41（θ = 0.2，α = 1.0），对于D13S128为1.54（θ = 0，α = 0.3），附近的标记也产生了阳性A - lod分数。当对白种人样本应用五点无模型连锁分析时，在位于13号染色体q32的标记D13S122和D13S128周围获得了最大lod分数2.58。东方人群组的连锁结果不如白种人群组积极。我们的结果再次表明，在13号染色体q14.1 - q32区域存在精神分裂症的潜在易感基因座，尤其是在白种人群体中。
