Despite considerable research, fundamental questions about CFS-like illness remain at best partially answered. These questions include its definition, validity, the degree to which it results from genetic versus environmental factors, and the nature of the substantial comorbidity observed with other conditions. The overarching aim of this Project is to shed light on a number of basic questions about CFS via a large population-based classical twin study. First, we will screen approximately 13,000 same-sex twin pairs who are members of the Mid-Atlantic Twin Registry for the lifetime presence of CFS-like illness (and several overlapping conditions such as fibromyalgia and major depression). Second, all twins who screen positive and a subset of twins who screen negative will be directly and blindly interviewed. The interviews will collect information about CFS symptoms, psychiatric disorders, stress life events, and medical history, and medical history. We will obtain additional standardized medical data via the subject's physician(s). Third, all screening, direct interview and medical data will be independently reviewed by three of the study investigators to determine the certainty than an individual meets criteria for """"""""presumptive CFS"""""""" plus approximations of the Centers for Disease Control, British, and Australian CFS case definitions. Obtaining these unique data will allow us to address a set of critical questions regarding CFS-like illness. First, using the direct interview data will allow us to address a set of critical questions regarding CFS-like illness. First, using the direct interview data, we will use multivariate techniques to derive and empirical typology of prolonged fatigue and to assess how this typology compares to the major CFS case definitions to answer the question: """"""""Is there a point of rarity that distinguishes the common symptom of fatigue from case definitions of CFS""""""""? Next, we will quantify the role of genetic predisposition and environmental sources of variation from different definitions of CFS-like illness. This will allow us to address 2 important questions. Because the degree to which a complex and idiopathic condition is heritable is an important validator, we can address the question: """"""""Do these definitions yield similar or different estimates of heritability?"""""""" In addition, examining the extent to which liability to CFS- like illness is due to additive genetic, shared environmental, and individual-specific environmental precipitating effects will yield glimpses into the fundamental nature of CFS. Finally, using multivariate twin analyses, we address the question: """"""""To what extent to the genetic and environmental sources of variation of these other conditions overlap with CFS?""""""""
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