College of Public Health, Research Center for Genes and Institute of Epidemiology and Preventive Medicine, Environment and Human Health, National Taiwan University, Taipei, Taiwan.
PLoS One. 2011;6(8):e24103. doi: 10.1371/journal.pone.0024103. Epub 2011 Aug 29.
As schizophrenia is genetically and phenotypically heterogeneous, targeting genetically informative phenotypes may help identify greater linkage signals. The aim of the study is to evaluate the genetic linkage evidence for schizophrenia in subsets of families with earlier age at onset or greater neurocognitive deficits.
Patients with schizophrenia (n = 1,207) and their first-degree relatives (n = 1,035) from 557 families with schizophrenia were recruited from six data collection field research centers throughout Taiwan. Subjects completed a face-to-face semi-structured interview, the Continuous Performance Test (CPT), the Wisconsin Card Sorting Test, and were genotyped with 386 microsatellite markers across the genome.
A maximum nonparametric logarithm of odds (LOD) score of 4.17 at 2q22.1 was found in 295 families ranked by increasing age at onset, which had significant increases in the maximum LOD score compared with those obtained in initial linkage analyses using all available families. Based on this subset, a further subsetting by false alarm rate on the undegraded and degraded CPT obtained further increase in the nested subset-based LOD on 2q22.1, with a score of 7.36 in 228 families and 7.71 in 243 families, respectively.
We found possible evidence of linkage on chromosome 2q22.1 in families of schizophrenia patients with more CPT false alarm rates nested within the families with younger age at onset. These results highlight the importance of incorporating genetically informative phenotypes in unraveling the complex genetics of schizophrenia.
由于精神分裂症在遗传和表型上存在异质性，针对具有遗传信息的表型可能有助于确定更大的连锁信号。本研究的目的是评估具有发病年龄较早或神经认知缺陷较大的亚组家庭中精神分裂症的遗传连锁证据。
从台湾 6 个数据收集现场研究中心的 557 个精神分裂症家庭中招募了精神分裂症患者（n = 1,207）及其一级亲属（n = 1,035）。受试者完成了面对面的半结构化访谈、连续性能测试（CPT）、威斯康星卡片分类测试，并通过基因组上的 386 个微卫星标记进行了基因分型。
在按发病年龄递增排序的 295 个家庭中，发现了最大非参数对数优势（LOD）评分 4.17 的 2q22.1，与使用所有可用家庭进行的初始连锁分析相比，该评分显著增加。基于该亚组，在未降级和降级 CPT 的虚报率的进一步亚组化中，2q22.1 上的嵌套亚组基于 LOD 进一步增加，在 228 个家庭和 243 个家庭中分别得到 7.36 和 7.71 的评分。
我们在发病年龄较早的家庭中发现了 2q22.1 染色体上可能存在的连锁证据，这些家庭中嵌套了更多 CPT 虚报率的亚组。这些结果强调了在揭示精神分裂症复杂遗传学方面，纳入具有遗传信息的表型的重要性。
