Genetic studies based on linkage suggest genetic overlap among different autoimmune diseases

Beginning in the 1990s many groups began to perform linkage studies in order to identify chromosomal regions that harbor risk genes for autoimmune diseases. In general, these studies took the form of affected sibling pair analyses, in which there is an attempt to identify genetic regions that are shared among affected siblings more frequently than expected by chance. This approach to genetic analysis is discussed in more detail by Worthington (see Chapter 2). In general, affected sibling pair analysis suffers from lack of statistical power, and therefore requires very large numbers of families in order to provide 'definite' evidence for linkage to a particular genetic region [33]. Nevertheless, the combined data have suggested that common genetic regions may be involved across different autoimmune disorders [34]. More recent data continue to suggest that lupus, type 1 diabetes and rheumatoid arthritis appear to have some areas of overlap involving particularly certain regions of chromosomes 1q, 2q, and 6q, among others [35-39]. However, the evidence of linkage in all cases is modest, and not always replicated. In addition, each of these linkage regions contain large numbers of potential candidate genes, and the genes involved in the different disorders may well be quite different, even within the same linkage region. Thus, while there was considerable early interest in these overlapping linkage results, it is not clear how significant these findings really are, and they do not in and of themselves provide a strong case for a common genetic basis for autoimmune disorders.

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