title: Evaluating disorders with a complex genetics basis. the future roles of meta-analysis and systems biology.
abstract: Growing evidence suggests that complex gene and environment interactions underlie a number of diseases including chronic inflammatory diseases of the digestive system. The rapid advances in information and technology provide opportunities to discover the risks or etiology for a variety of disorders within individual patients. However, the availability of new data and new technology has outstripped the conceptual framework of simple disorders and challenges current statistical approaches. Here we address the issues surrounding study design and sample size for complex genetic traits, with special attention to meta-analysis and systems biology. We conclude that meta-analysis should play a limited role in evaluating studies of complex genetic diseases. Instead, systems biology-based approaches should be developed to integrate multiple, focused, and mechanistic association studies with the goal of assisting in the risk assessment of patients on a person-by-person basis.
authors.affiliation: Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA. whitcomb@pitt.edu
authors.forename: David C
authors.initials: DC
authors.lastname: Whitcomb
authors.forename: Elie
authors.initials: E
authors.lastname: Aoun
authors.forename: Yoram
authors.initials: Y
authors.lastname: Vodovotz
authors.forename: Gilles
authors.initials: G
authors.lastname: Clermont
authors.forename: M Michael
authors.initials: MM
authors.lastname: Barmada
mesh_terms: D005544:Forecasting; D005767:Gastrointestinal Diseases / Q000453:epidemiology* / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D006801:Humans; D015994:Incidence; D015201:Meta-Analysis as Topic; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D049490:Systems Biology