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Segregation analysis indicated that patterns of familial clustering are best explained by transmission of a major autosomal dominant gene with reduced penetrance and a multifactorial component. However, the single major locus model could be rejected in favour of the mixed model only when a cohort effect for heritability was allowed for. The frequency of the AD susceptibility allele was estimated to be 0.48% in the single major locus model and 0.31% in the mixed model. Although our study confirms that a dominant major gene is implicated in early onset AD, the results suggest that other genetic or perhaps non-genetic factors may account for the disease in a considerable number of patients.<\/jats:p>","DOI":"10.1136\/jmg.30.8.640","type":"journal-article","created":{"date-parts":[[2008,11,10]],"date-time":"2008-11-10T15:23:16Z","timestamp":1226330596000},"page":"640-646","source":"Crossref","is-referenced-by-count":19,"title":["Genetic transmission of Alzheimer's disease among families in a Dutch population based study."],"prefix":"10.1136","volume":"30","author":[{"given":"C M","family":"van Duijn","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L A","family":"Farrer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L A","family":"Cupples","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Hofman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[1993,8,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/0197-4580(89)90082-1","article-title":"Familial Alzheimer's disease: progress and problems","volume":"10","author":"PH, St George-Hyslop; RH, Myers; JL, Haines","year":"1989","unstructured":"St George-Hyslop PH, Myers RH, Haines JL, et al. 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