Linkage analysis of schizophrenia controlling for population substructure.
Linkage analysis of schizophrenia controlling for population substructure.
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精神分裂症控制人口亚结构的连锁分析。
DOI：
10.1002/ajmg.b.30905
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Varilo,Teppo
中科院分区：
文献类型：
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作者：
Paunio,Tiina;Arajärvi,Ritva;Terwilliger,JosephD;Hiekkalinna,Tero;Haimi,Perttu;Partonen,Timo;Lönnqvist,Jouko;Peltonen,Leena;Varilo,Teppo
病因学的异质性和复杂性阻碍了鉴定精神分裂症易感基因的尝试。我们试图通过关注疾病患病率较高的群体分离来最大程度地减少所涉及的分离基因的数量。我们利用既定的人口历史，在两个不同的创始人谱系的家族中寻找疾病易感位点。我们研究了来自芬兰东部边境的一个边远城市的 28 个精神分裂症谱系（123 个核心家庭）。我们根据家谱对家庭进行划分，并定义了两条移民路线：南部和北部。我们检查了每组内的亲缘系数和等位基因频率分布，并基于基因组中的 497 个微卫星标记进行了连锁分析。正如预期的那样，等位基因的共享程度高于我们仅在前四代中确定的关系所预测的水平，证明了高度的历史相关性。在两个亚群之间，等位基因频率存在显着差异，这与其孤立的谱系一致。南方家庭在 4q23 (Z 1/4 3.3) 处的精神分裂症基因座中显示出一些关联证据，与我们之前的发现与语言学习和记忆的定量变化接近[Paunio et al.(2004)； Hum Mol Genet 13: 1693–1702]，而北方谱系在 10q21 (Z ¼ 2.53) 上提供了最重要的证据。对两个谱系的家族进行联合分析表明，仅在 3p14 (Z ¼ 3.18) 存在关联证据。因此，详细的谱系信息使我们在我们进行的三项分析之间识别出精神分裂症易感基因座的不同连锁信号。 Ó2008 Wiley-Liss, Inc.
Etiological heterogeneity and complexity has hampered attempts to identify predisposing genes for schizophrenia. We sought to minimize the number of segregating genes involved by focusing on a population isolate with elevated disease prevalence. We exploited the well-established population history, and searched for disease susceptibility loci in families from two alternative founder lineages. We studied 28 schizophrenia pedigrees (123 nuclear families) from an outlying municipality on the eastern border of Finland. We divided the families based on their genealogy and defined two routes of immigration: southern and northern. We examined the kinship coefficients and allele frequency distributions within each group, and performed a linkage analysis based on 497 microsatellite markers across the genome. A high degree of historical relatedness was demonstrated by higher sharing of alleles than predicted by the relationships we identified within the previous four generations alone, as would be expected. Between the two subpopulations, allele frequencies were significantly different, consistent with their isolated genealogies. The southern families showed some evidence of linkage in a schizophrenia locus at 4q23 (Z ¼ 3.3) near our previous finding with quantitative variation in verbal learning and memory [Paunio et al.(2004); Hum Mol Genet 13: 1693–1702], while the northern pedigrees gave most significant evidence on 10q21 (Z ¼ 2.53). Joint analysis of families from both lineages suggested evidence of linkage only at 3p14 (Z ¼ 3.18). Thus the detailed genealogical information led us to identification of distinct linkage signals for schizophrenia susceptibility loci between the three analyses we performed. Ó2008 Wiley-Liss, Inc.