Symptom dimensions of schizophrenia are likely to be the intermediate phenotypes under the control of disease-susceptibility genes, or separate traits related to disease-modifier genes. This study aimed to identify chromosomal loci linked to symptom dimensions of schizophrenia through genome-wide quantitative trait locus (QTL) linkage analysis. The study subjects consisted of 56 families with 183 members including 123 affected individuals. Symptom evaluations were performed on lifetime basis. Through principal component factor analysis, eight quantitative phenotypes representing symptom dimensions were identified. Genotyping was done for 6008 SNP markers, and genome-wide QTL linkage analysis was performed. No symptom dimension showed a significant linkage attaining genome-wide empirical thresholds. We observed seven regions yielding linkage signals attaining genome-wide empirical thresholds for suggestive linkage (NPL Z score = 2.78-3.49); chromosome 15q26.1 for 'non-paranoid delusion factor', 2p24.3 and 7q31.1 for 'prodromal impairment factor', 1q32.1, 9p21.3, and 9q31.2 for 'negative symptom factor', and 10p13 for 'disorganization factor'. Among these loci, chromosome 2p24.3 and 1q32.1 overlap with susceptibility loci of schizophrenia identified in our previous linkage studies. This study suggests the existence of genetic loci related to various clinical features of schizophrenia. Further genetic analyses for these dimensional phenotypes are warranted.

译文

:精神分裂症的症状表现可能是疾病易感性基因或与疾病调节基因相关的单独性状控制下的中间表型。这项研究旨在通过全基因组定量特征位点(QTL)连锁分析来确定与精神分裂症症状维度相关的染色体基因座。研究对象包括56个家庭,有183名成员,其中包括123个人。症状评估是基于终生进行的。通过主成分因子分析,确定了代表症状维度的八种定量表型。对6008个SNP标记进行了基因分型,并进行了全基因组QTL连锁分析。没有症状维度显示达到全基因组经验阈值的显着联系。我们观察到七个区域产生连锁信号,达到暗示性连锁的全基因组经验阈值(NPL Z评分= 2.78-3.49);染色体15q26.1代表'非偏执妄想因子',2p24.3和7q31.1代表'前驱性损伤因子',1q32.1、9p21.3和9q31.2代表'阴性症状因子',10p13代表'混乱因素”。在这些基因座中,染色体2p24.3和1q32.1与我们先前的连锁研究中确定的精神分裂症易感基因座重叠。这项研究表明存在与精神分裂症的各种临床特征有关的遗传基因座。这些维度表型的进一步遗传分析是必要的。

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