Finding suitable phenotypes for genetic studies of schizophrenia: Heritability and segregation analysis
Finding suitable phenotypes for genetic studies of schizophrenia: Heritability and segregation analysis
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DOI：
10.1016/j.biopsych.2007.12.013
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发表时间：
2008-07-15
影响因子：
10.6
通讯作者：
Kahn, Rene S.
中科院分区：
文献类型：
--
作者：
Aukes, Maartje F.;Alizadeh, Behrooz Z.;Kahn, Rene S.
背景：精神分裂症是一种高度遗传的复杂疾病。可能涉及多个基因，使对这种疾病病因的遗传学研究复杂化。如果中间表型或内在表型显示出比精神分裂症本身更简单的传播模式，即，如果他们更密切地反映了潜在的遗传effects.Methods：25个多代家庭的多个成员患有精神分裂症（180名受试者）进行了广泛的神经心理学，心理生理学和人格测试电池。计算家族相关性以选择可遗传性状。随后进行混合和分离分析的遗传力分析，以解开的传输模式，估计heritive.Results：五个性状，包括感觉运动门控，开放性，言语流畅性，早期视觉感知，空间工作记忆，表现出中度的家族相关。这些性状的遗传力估计为37%至54%。一个主要的基因模型，类似显性传播被发现的感觉运动门控和开放性。言语流畅性，早期视觉感知和空间工作记忆可能是占多基因，多因素，或environmentaleffects.Conclusions：只有2的13个候选endophenotypes显示了一个简单的传输模式，成功的应用分子遗传学研究：感觉运动门控和开放性。据我们所知，这是第一个研究这些特征的传播模式的研究。
Background: Schizophrenia is a highly heritable and complex disorder. Multiple genes are likely to be involved, complicating genetic research into the etiology of this disorder. Intermediate phenotypes or endophenotypes may facilitate genetic research if they display a simpler mode of transmission than schizophrenia itself, i.e., if they reflect more closely the underlying genetic effects.Methods: Twenty-five multigenerational families with multiple members affected with schizophrenia (180 subjects) were administered an extensive neuropsychological, psychophysiological, and personality test battery. Familial correlations were calculated to select heritable traits. Subsequent heritability analysis followed by commingling and segregation analysis were performed to unravel the pattern of transmission and to estimate heritability.Results: Five traits, including sensorimotor gating, openness, verbal fluency, early visual perception, and spatial working memory, showed moderate familial correlations. Heritability estimates for these traits ranged from 37% to 54%. A major gene model resembling dominant transmission was found for both sensorimotor gating and openness. Verbal fluency, early visual perception, and spatial working memory may be accounted for by polygenic, multifactorial, or environmental effects.Conclusions: Only 2 of 13 candidate endophenotypes showed a simple mode of transmission useful for successful application in molecular genetic research: sensorimotor gating and openness. To our knowledge, this is the first study to investigate the pattern of transmission for these traits.