Melhem Nadine M, Lu Cong, Dresbold Cara, Middleton Frank A, Klei Lambertus, Wood Shawn, Faraone Stephen V, Vinogradov Sophia, Tiobech Josepha, Yano Victor, Roeder Kathryn, Byerley William, Myles-Worsley Marina, Devlin Bernie
Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
Am J Med Genet B Neuropsychiatr Genet. 2014 Sep;165B(6):521-30. doi: 10.1002/ajmg.b.32255. Epub 2014 Jul 1.
An increased abundance of runs of homozygosity (ROH) has been associated with risk for various diseases, including schizophrenia. Here we investigate the characteristics of ROH in Palau, an Oceanic population, evaluating whether these characteristics are related to risk for psychotic disorders and the nature of this association. To accomplish these aims we evaluate a sample of 203 cases with schizophrenia and related psychotic disorders-representing almost complete ascertainment of affected individuals in the population-and contrast their ROH to that of 125 subjects chosen to function as controls. While Palauan diagnosed with psychotic disorders tend to have slightly more ROH regions than controls, the distinguishing features are that they have longer ROH regions, greater total length of ROH, and their ROH tends to co-occur more often at the same locus. The nature of the sample allows us to investigate whether rare, highly penetrant recessive variants generate such case-control differences in ROH. Neither rare, highly penetrant recessive variants nor individual common variants of large effect account for a substantial proportion of risk for psychosis in Palau. These results suggest a more nuanced model for risk is required to explain patterns of ROH for this population.
纯合子连续片段（ROH）丰度增加与包括精神分裂症在内的多种疾病风险相关。在此，我们研究了大洋洲帕劳人群中ROH的特征，评估这些特征是否与精神障碍风险及其关联性质有关。为实现这些目标，我们评估了203例精神分裂症及相关精神障碍患者的样本——几乎涵盖了该人群中所有确诊的患者——并将他们的ROH与125名作为对照的受试者的ROH进行对比。虽然被诊断患有精神障碍的帕劳人往往比对照组有略多的ROH区域，但显著特征是他们的ROH区域更长，ROH总长度更大，且他们的ROH更倾向于在同一基因座共现。该样本的性质使我们能够研究罕见的、高外显率的隐性变异是否会导致ROH出现这种病例对照差异。在帕劳，罕见的、高外显率的隐性变异和单个有显著效应的常见变异都不能解释很大一部分精神病风险。这些结果表明，需要一个更细致入微的风险模型来解释该人群的ROH模式。
