Analysis of the threshold liability model provides new understanding of causation in autoimmune diseases

Medical Hypotheses
D G Haegert

Abstract

Autoimmune diseases include a heterogeneous group of complex traits, the causes of which are essentially unknown. The threshold liability model is a hypothesis that has a significant influence on thinking about causation in these diseases. Here, I analyze this model and assess its utility in understanding causation in autoimmunity. According to the model, members of a population have a normal distribution of genetic liability for a particular autoimmune disease. Further, a threshold value exists for each autoimmune disease such that an individual develops disease when his/her liability exceeds the threshold value; environmental and stochastic factors and epistatic gene interactions may increase or decrease an individual's disease liability. There are, however, two main problems with the threshold liability model. First, for a particular autoimmune disease, the threshold value divides a population into two distinct groups that consist either of affected or of healthy individuals. I show that this dichotomous division is inaccurate and misleading. Second, the threshold value corresponds to the occurrence of a component-cause of disease, i.e. when an appropriate collection of causative factors for a particular autoimmune disease i...Continue Reading

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Citations

Feb 28, 2007·Leukemia & Lymphoma·Guillermo J Ruiz-ArgüellesJavier Garcés-Eisele
Jan 3, 2009·Nature Reviews. Genetics·Greg Gibson
Apr 25, 2012·Hematology·Alejandro Ruiz-Arguelles

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Autoimmune Diseases

Autoimmune diseases occur as a result of an attack by the immune system on the body’s own tissues resulting in damage and dysfunction. There are different types of autoimmune diseases, in which there is a complex and unknown interaction between genetics and the environment. Discover the latest research on autoimmune diseases here.

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