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To cope with this situation, a risk\u2010factor model based on standard epidemiologic designs is proposed. The model supposes that adding a factor to a fixed set of existing factors always increases the total risk. Thus, according to the model genetic contributions cumulate but are not necessarily additive. A threshold, hence, epistasis is required. The model is applied to several conditions in which the risk of autism is elevated, some genetic (fragile X, tuberous sclerosis) and some exogenous (rubella and thalidomide embryopathies). Male gender is discussed as a risk factor. This approach is contrasted primarily with Gillberg and Coleman's view of autism as \u201ca syndrome or series of syndromes caused by many different separate individual diseases.\u201d The principal point of difference is whether the effects of different causes cumulate or do not cumulate. In the present approach they do, in Gillberg and Coleman's they do not. \u00a9 2002 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.10513","type":"journal-article","created":{"date-parts":[[2002,10,6]],"date-time":"2002-10-06T12:29:56Z","timestamp":1033907396000},"page":"558-565","source":"Crossref","is-referenced-by-count":34,"title":["A risk\u2010factor model of epistatic interaction, focusing on autism"],"prefix":"10.1002","volume":"114","author":[{"given":"Marshall 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