Evidence for a schizophrenia vulnerability locus on chromosome 8p in the Irish Study of High-Density Schizophrenia Families.
Evidence for a schizophrenia vulnerability locus on chromosome 8p in the Irish Study of High-Density Schizophrenia Families.
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DOI：
10.1176/ajp.153.12.1534
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发表时间：
1996-12
期刊：
影响因子：
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通讯作者：
K. Kendler;C. Maclean;F. O’Neill;J. Burke;B. Murphy;Fiona Duke;R. Shinkwin;S. M. Easter;B. Webb;J. Zhang;D. Walsh;R. Straub
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文献类型：
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作者：
K. Kendler;C. Maclean;F. O’Neill;J. Burke;B. Murphy;Fiona Duke;R. Shinkwin;S. M. Easter;B. Webb;J. Zhang;D. Walsh;R. Straub
目的本研究试图复制Pulver及其同事报道的精神分裂症和相关疾病在8 p22 -21区域的易感位点的证据。方法爱尔兰高密度精神分裂症家族研究的连锁样本包括265个多重家族，包含1,408个个体。对染色体8 p上覆盖30厘摩的15个标记进行了检测。采用三种统计方法：两点和多点异质性lod评分和多点非参数检验。结果根据两点异质性lod得分，最强的证据发现连锁标记D8 S1731（最大lod得分= 2.00），D8 S1715（最大lod得分= 2.52），和D8 S133（最大lod得分= 2.08），通过假设所有精神疾病的表型定义和一系列的遗传模型。根据多点异质性lod分数，最强有力的证据连锁（最大lod分数= 2.34），发现通过使用显性遗传模型和精神分裂症谱的广泛定义，扩展到10厘米的区域之间的标记D8 S1715和D8 S1739。多点非参数连锁发现最强的证据（最大z = 2.51）在更广泛的区域时，无论是核心精神分裂症的诊断或精神分裂症谱的狭义定义。这个假定的脆弱性位点在10%-25%的家庭中分离。结论本研究支持精神分裂症易感基因在染色体8 p上的存在。在这个样本中，这个基因座似乎只影响了一小部分家庭的患病风险，并易患一系列精神分裂症谱系和可能的非谱系障碍。
OBJECTIVE This study was an attempt to replicate evidence for a vulnerability locus for schizophrenia and associated disorders in the 8p22-21 region reported by Pulver and colleagues. METHOD The linkage sample of the Irish Study of High-Density Schizophrenia Families consists of 265 multiplex families containing 1,408 individuals. Fifteen markers covering 30 centimorgans on chromosome 8p were tested. Three statistical methods were used: two-point and multipoint heterogeneity lod scores and a multipoint nonparametric test. RESULTS According to two-point heterogeneity lod scores, the strongest evidence for linkage was found for markers D8S1731 (maximum lod score = 2.00), D8S1715 (maximum lod score = 2.52), and D8S133 (maximum lod score = 2.08) by assuming a phenotypic definition of all psychiatric illness and a range of genetic models. According to multipoint heterogeneity lod scores, the strongest evidence for linkage (maximum lod score = 2.34), found by using a dominant genetic model and a broad definition of the schizophrenia spectrum, extended over a 10-cM region between markers D8S1715 and D8S1739. Multipoint nonparametric linkage found the strongest evidence (maximum z = 2.51) over a broader region when either a diagnosis of core schizophrenia or a narrow definition of the schizophrenia spectrum was used. This putative vulnerability locus was segregating in 10%-25% of the families studied. CONCLUSIONS This study supports the existence of a vulnerability locus for schizophrenia on chromosome 8p. In this sample, this locus appears to influence the risk of illness in only a modest proportion of families and predisposes to a range of schizophrenia spectrum and possibly nonspectrum disorders.