Hovatta I, Varilo T, Suvisaari J, Terwilliger J D, Ollikainen V, Arajärvi R, Juvonen H, Kokko-Sahin M L, Väisänen L, Mannila H, Lönnqvist J, Peltonen L
Department of Human Molecular Genetics, National Public Health Institute, Helsinki, Finland.
Am J Hum Genet. 1999 Oct;65(4):1114-24. doi: 10.1086/302567.
Schizophrenia is a severe mental disorder affecting approximately 1% of the world's population. Here, we report the results from a three-stage genomewide screen performed in a study sample from an internal isolate of Finland. An effort was made to identify genes predisposing for schizophrenia that are potentially enriched in this isolate, which has an exceptionally high lifetime risk for this trait. Ancestors of the local families with schizophrenia were traced back to the foundation of the population in the 17th century. This genealogical information was used as the basis for the study strategy, which involved screening for alleles shared among affected individuals originating from common ancestors. We found four chromosomal regions with markers revealing pairwise LOD scores>1.0: 1q32.2-q41 (Z(max)=3.82, dominant affecteds-only model), 4q31 (Z(max)=2. 74, dominant 90%-penetrance model), 9q21 (Z(max)=1.95, dominant 90%-penetrance model), and Xp11.4-p11.3 (Z(max)=2.01, recessive 90%-penetrance model). This finding suggests that there are several putative loci predisposing to schizophrenia, even in this isolate.
精神分裂症是一种严重的精神障碍,影响着全球约1%的人口。在此,我们报告了在芬兰一个内部隔离群体的研究样本中进行的三阶段全基因组筛查结果。我们致力于识别在该隔离群体中可能富集的、导致精神分裂症的基因,该群体患此疾病的终生风险异常高。患有精神分裂症的当地家族的祖先可追溯到17世纪该群体形成之时。这些系谱信息被用作研究策略的基础,该策略包括筛查来自共同祖先的受影响个体之间共享的等位基因。我们发现了四个染色体区域,其标记显示成对的对数优势分数>1.0:1q32.2-q41(Z(最大值)=3.82,仅显性受影响模型)、4q31(Z(最大值)=2.74,显性90%外显率模型)、9q21(Z(最大值)=1.95,显性90%外显率模型)和Xp11.4-p11.3(Z(最大值)=2.01,隐性90%外显率模型)。这一发现表明,即使在这个隔离群体中,也存在多个可能导致精神分裂症的基因座。