Universal risk factors for multifactorial diseases

• DOI: 10.1007/s10654-007-9204-4
• Publication Date: 2007-12-12T03:24:01Z
• Authors: Ronald P. Stolk; Judith G. M. Rosm...; Dirkje S. Postma; Rudolf A. de Boer; Gerjan Navis; Joris P. J. Slaets; Johan Ormel; Bruce H. R. Wolff...
• Keywords: Genetic predisposition

The risk for multifactorial diseases is determined by factors that frequently apply across disorders (universal factors). To investigate unresolved issues on etiology of and individual's susceptibility to diseases, research focus should shift from single determinant-outcome relations effect modification universal factors. We present a model based factor, outcome measure, several modifiers. Outcome measures can be disease overriding, such as clustering disease, frailty quality life. "Life course epidemiology" considered specific application the proposed model, since modifiers typically have chronic aspect. Risk are categorized into genetic, environmental, or complex factors, latter resulting interactions between (multiple) genetic environmental (an example factor overweight). assumes differ individuals because modifiers, which divided three categories. First, risk-factor determine determinant (such modify gene-expression in case determinant). Second, expression studied medication use). Third, generic age). A study assess during life requires phenotype measurements multiple generations with long-term follow up. Multiple will also enable separate Traditionally, representative (probands) their first-degree relatives been included this type research. put forward three-generation design optimal approach diseases. This has statistical advantages (precision, multiple-informants, separation non-genetic familial transmission, direct haplotype assessment, quantify effects), enables unique possibilities social characteristics (socioeconomic mobility, partner preferences, between-generation similarities), offers practical benefits (efficiency, lower non-response). LifeLines these concepts. It carried out sample 165,000 participants northern provinces Netherlands. contribute understanding how modified influence individual not only at one stage but cumulatively over time: lifeline.