Use of a quantitative trait to map a locus associated with severity of positive symptoms in familial schizophrenia to chromosome 6p
Use of a quantitative trait to map a locus associated with severity of positive symptoms in familial schizophrenia to chromosome 6p
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DOI：
10.1086/301623
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发表时间：
1997-12-01
影响因子：
9.8
通讯作者：
Bassett, AS
中科院分区：
文献类型：
--
作者：
Brzustowicz, LM;Honer, WG;Bassett, AS
最近的一些连锁研究表明，在染色体6p上存在精神分裂症易感基因座。我们评估了28个遗传标记，跨越6号染色体，连锁精神分裂症在10个中等规模的加拿大凯尔特血统的家庭。根据常染色体显性和隐性模型，使用广义和狭义的精神分裂症的定义，这些家庭的参数分析，没有显着的连锁证据。使用分类疾病定义的同胞对分析也未能产生显著的联系证据。然后，我们进行了一个单独的同胞对分析，使用得分的阳性症状（精神病性），阴性症状（赤字），和一般的精神病理学症状量表的数量性状。D 6S 1960在两点分析和多点分析中的正向量表得分分别为P = 1.2 × 10（-5）和P = 5.4 × 10（-6）。通过模拟研究，我们确定这些标称P值分别对应于0.034和0.0085的经验P值。这些结果表明，精神分裂症的易感基因位点染色体6p可能与精神病症状的严重程度。行为数量性状的评估可能会提供更大的权力，在复杂的精神疾病的连锁检测分类表型分配。
A number of recent linkage studies have suggested the presence of a schizophrenia susceptibility locus on chromosome 6p. We evaluated 28 genetic markers, spanning chromosome 6; for linkage to schizophrenia in 10 moderately large Canadian families of Celtic ancestry. Parametric analyses of these families under autosomal dominant and recessive models, using broad and narrow definitions of schizophrenia, produced no significant evidence for linkage. A sib-pair analysis using categorical disease definitions also failed to produce significant evidence for linkage. We then conducted a separate sib-pair analysis using scores on positive-symptom (psychotic), negative-symptom (deficit), and general psychopathology-symptom scales as quantitative traits. With the positive symptom-scale scores, the marker D6S1960 produced P = 1.2 x 10(-5) under two-point and P = 5.4 x 10(-6) under multipoint analyses. Using simulation studies, we determined that these nominal P values correspond to empirical P values of .034 and .0085, respectively. These results suggest that a schizophrenia susceptibility locus on chromosome 6p may be related to the severity of psychotic symptoms. Assessment of behavioral quantitative traits may provide increased power over categorical phenotype assignment for detection of linkage in complex psychiatric disorders.