title: Primary Immunodeficiencies and Inflammatory Disease: A Growing Genetic Intersection.
abstract: Recent advances in genome analysis have provided important insights into the genetic architecture of infectious and inflammatory diseases. The combined analysis of loci detected by genome-wide association studies (GWAS) in 22 inflammatory diseases has revealed a shared genetic core and associated biochemical pathways that play a central role in pathological inflammation. Parallel whole-exome sequencing studies have identified 265 genes mutated in primary immunodeficiencies (PID). Here, we examine the overlap between these two data sets, and find that it consists of genes essential for protection against infections and in which persistent activation causes pathological inflammation. Based on this intersection, we propose that, although strong or inactivating mutations (rare variants) in these genes may cause severe disease (PIDs), their more subtle modulation potentially by common regulatory/coding variants may contribute to chronic inflammation.
authors.affiliation: Department of Biochemistry, Complex Traits Group, McGill University, Montreal, QC, Canada.
authors.forename: Nassima
authors.initials: N
authors.lastname: Fodil
authors.affiliation: Department of Biochemistry, Complex Traits Group, McGill University, Montreal, QC, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Langlais
authors.affiliation: Department of Biochemistry, Complex Traits Group, McGill University, Montreal, QC, Canada. Electronic address: philippe.gros@mcgill.ca.
authors.forename: Philippe
authors.initials: P
authors.lastname: Gros
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics*; D059472:Exome / Q000276:immunology; D056426:Genetic Loci / Q000276:immunology*; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D012306:Risk