Genetics of complex diseases: variations on a theme
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Updated: May 24, 2026

Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation
Published on: January 16, 2019
Erling Mellerup1, Gert Lykke Møller, Pernille Koefoed
1Laboratory of Neuropsychiatry, Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark. mellerup@sund.ku.dk
Abstract:
A complex disease with an inheritable component is polygenic, meaning that several different changes in DNA are the genetic basis for the disease. Such a disease may also be genetically heterogeneous, meaning that independent changes in DNA, i.e. various genotypes, can be the genetic basis for the disease. Each of these genotypes may be characterized by specific combinations of key genetic changes. It is suggested that even if all key changes are found in genes related to the biology of a certain disease, the number of combinations may be so large that the number of different genotypes may be close to the number of patients suffering from the disease. This hypothesis is based on a study of bipolar disorder.
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