Relationship between a high-risk haplotype in the DTNBP1 (dysbindin) gene and clinical features of schizophrenia
Relationship between a high-risk haplotype in the DTNBP1 (dysbindin) gene and clinical features of schizophrenia
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DOI：
10.1176/appi.ajp.162.10.1824
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发表时间：
2005-10-01
影响因子：
17.7
通讯作者：
Kendler, KS
中科院分区：
文献类型：
--
作者：
Fanous, AH;van den Oord, EJ;Kendler, KS
目的：本研究的目的是确定以前与精神分裂症相关的抗坏蛋白结合蛋白 1 (DTNBP1) 基因中的单倍型是否不仅会增加对精神疾病的易感性，而且还会增加对或多或少临床特定形式的精神疾病的易感性。方法：在爱尔兰高密度精神分裂症家族研究中，根据精神疾病受试者 (N=755) 的临床特征进行终生评级精神病操作标准清单。使用探索性和验证性因素分析来提取五个因素——幻觉、妄想、消极、躁狂和抑郁症状——并创建因素衍生评分。 TRANSMIT 程序中实施的基于家庭的传递不平衡测试用于确定 DTNBP1 基因中的高风险单倍型是否过度传递给每个因子得分处于上 20 个和 40 个百分位的受试者。通过检查 5,000 个重复组中的卡方统计数据的经验分布，将这些结果与基线过度传播进行比较，其中随机选择 20% 和 40% 的患病受试者。这项分析是针对精神病的狭义和广义定义进行的。结果：阴性症状因素位于上 40 个百分位的受试者（在狭义 (p=0.004) 和广义 (p=0.01) 定义的疾病组中）比偶然预期的更有可能遗传高风险单倍型。没有观察到临床特征和高风险单倍型传播之间的其他显着关系。结论：DTNBP1 的病因学相关变异与高风险单倍型处于假定的连锁不平衡状态，可能使个体易患某种与高水平阴性症状相关的精神病。这一发现支持了先前的证据，表明遗传因素影响精神分裂症的临床异质性。
Objective: The purpose of this study was to determine whether a haplotype in the dystrobrevin binding protein 1 (DTNBP1) gene previously associated with schizophrenia not only increases the susceptibility to psychotic illness but also to a more or less clinically specific form of psychotic illness.Method: In the Irish Study of High-Density Schizophrenia Families, subjects with psychotic illness (N=755) were given lifetime ratings of clinical features according to the Operational Criteria Checklist for Psychotic Illness. Exploratory and confirmatory factor analyses were used to extract five factors-hallucinations, delusions, negative, manic, and depressive symptoms-and to create factor-derived scores. The family-based transmission disequilibrium test operationalized in the program TRANSMIT was used to determine whether a high-risk haplotype in the DTNBP1 gene was overtransmitted to subjects in the upper 20th and 40th percentiles for each factor score. These results were compared to baseline overtransmission by examining the empirical distribution of chi-square statistics in groups of 5,000 replicates in which 20% and 40% of ill subjects were randomly selected. This analysis was done for both narrow and broad definitions of psychotic illness. Results: Subjects in the upper 40th percentile for the negative symptom factor-in both the narrowly (p=0.004) and broadly (p=0.01) defined illness groups-were more likely to inherit the high-risk haplotype than would be expected by chance. No other significant relationships between clinical features and high-risk haplotype transmission were observed.Conclusions: The etiologically relevant variation in DTNBP1, which is in presumptive linkage disequilibrium with the high-risk haplotype, may predispose individuals to a form of psychotic illness associated with high levels of negative symptoms. This finding supports previous evidence suggesting that genetic factors influence the clinical heterogeneity of schizophrenia.