Heritability for Alzheimer's disease: The study of dementia in Swedish twins
Heritability for Alzheimer's disease: The study of dementia in Swedish twins
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DOI：
10.1093/gerona/52a.2.m117
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发表时间：
1997-03-01
影响因子：
5.1
通讯作者：
Ahlbom, A
中科院分区：
文献类型：
--
作者：
Gatz, M;Pedersen, NL;Ahlbom, A
背景阿尔茨海默氏病被认为有家族性和散发性的形式，几个遗传缺陷已被确定，主要解释早发性家族病例。在这项研究中，我们的目的是在一个已建立的双胞胎登记处检测所有痴呆病例，并估计遗传对阿尔茨海默病易感性的总贡献程度。在第一阶段，使用面对面或电话精神状态测试对登记处的成员进行痴呆症筛查。在第二阶段，那些筛查结果呈阳性的人及其伴侣被转诊接受临床检查，包括神经心理学评估、医生检查、实验室检查和神经影像学检查。临床诊断在多学科共识会议上分配。通过接合性检查Probandwise一致率，并使用单阈值和多阈值模型对数据进行结构建模以估计遗传和环境影响。65对被鉴定为其中一人或两人都患有痴呆症。阿尔茨海默氏病的先证者一致率在同卵配对中为67%，异卵配对的相应数字为22%。阿尔茨海默病的遗传易感性估计为0.74;任何痴呆症的遗传易感性为0.43。其他差异是由于环境的影响。研究结果表明，这些主要是迟发性阿尔茨海默病病例的遗传效应很大。与此同时，结构建模结果和发病年龄的较大对内差异表明，环境因素在确定个体是否以及何时可能患上痴呆症方面也很重要。
Background. Alzheimer's disease has been thought to have familial and sporadic forms, and several genetic defects have been identified that chiefly explain early-onset familial cases. In this study, our purpose was to detect all cases of dementia in an established twin registry and to estimate total extent of genetic contribution to liability to Alzheimer's disease.Methods. At the first stage, members of the registry were screened for dementia, using in-person or telephone mental status testing. At the second stage, those who screened positively and their partners were referred for clinical work-ups, including neuropsychological assessment, physician examination, laboratory tests, and neuroimaging. Clinical diagnoses were assigned at a multidisciplinary consensus conference. Probandwise concordance rates were examined by zygosity, and structural modeling was applied to the data to estimate genetic and environmental influences, using both single- and multiple-threshold models.Results. Sixty-five pairs were identified in which one or both was demented. The probandwise concordance rate for Alzheimer's disease among monozygotic pairs was 67%; the corresponding figure for dizygotic pairs was 22%. Heritability of liability to Alzheimer's disease was estimated to be .74; to any dementia, .43. The other variance is attributable to environmental influences.Conclusions. Findings indicate a substantial genetic effect for these predominantly late-onset Alzheimer's disease cases. At the same time, structural modeling results and large intra-pair differences in age of onset suggest that environmental factors are also important in determining whether and when an individual may develop dementia.