This broader representation of complex disease, therefore, has implications for clinicians and researchers who are tasked with creating evidence-based and consensus-based recommendations and for public health tracking of complex disease. The Human Disease Ontology’s Complex Disease model offers a mechanism for defining more accurate disease classification as a tool for more precise clinical diagnosis. The model is robust and flexible to capture new information as the understanding of complex disease improves. Model assessment resulted in the reassessment of the three complex disease classifications and identified driving factors, thus improving the model. We provide a detailed rationale for a model representing the classification of complex disease using three test conditions of asthma, diabetes and fetal alcohol syndrome. Assessment of disease drivers for asthma, diabetes and fetal alcohol syndrome tested the model. The model was developed to provide a guide for capturing diverse mechanisms of complex diseases. Here we present a new approach for modeling complex diseases that integrates the multiple contributing genetic, epigenetic, environmental, host and social pathogenic effects causing disease. This model was developed to address the challenges of classifying complex diseases given the evolving nature of understanding of disease and interaction and contributions of genetic, environmental, and social factors. With the aim of enhancing the determination of key etiological factors, we developed and tested a complex disease model that encompasses diverse factors that in combination result in complex diseases. Complex diseases often present as a diagnosis riddle, further complicated by the combination of multiple phenotypes and diseases as features of other diseases.
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