GWAS implicates a role for quantitative immune traits and threshold effects in risk for human autoimmune disorders
2012
Gregersen, Peter K | Diamond, Betty | Plenge, Robert M
Genome wide association studies in human autoimmune disorders have provided a long list of alleles with rather modest degrees of risk. A large fraction of these associations are probably owing to either quantitative differences in gene expression or amino acid changes that regulate quantitative aspects of the immune response. While functional studies are still lacking for most of these associations, we present examples of autoimmune disease risk alleles that influence quantitative changes in lymphocyte activation, cytokine signaling and dendritic cell function. The analysis of immune quantitative traits associated with autoimmune loci is clearly going to be an important component of understanding the pathogenesis of autoimmunity. This will require both new and more efficient ways of characterizing the normal immune system, as well as large population resources in which genotype–phenotype correlations can be convincingly demonstrated. Future development of new therapies will depend on understanding the mechanistic underpinnings of immune regulation by these new risk loci.
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