Promise and pitfalls of the Immunochip 英文参考文献.docVIP

Cortes and Brown Arthritis Research Therapy 2011,13:101 /content/13/1/101 COMMENTARY Promise and pitfalls of the Immunochip Adrian Cortes and Matthew A Brown* Further, the true associated variants are uncertain for Abstract most identi? ed loci – even though GWAS have far better resolution than the linkage studies preceding the GWAS era. Even high-density mapping with common SNPs has in most cases not been able to distinguish an association signal due to direct association with disease risk from an indirect association signal due to linkage disequilibrium e? ects. Genomewide association studies (GWAS) have proven a powerful hypothesis-free method to identify common disease-associated variants. Even quite large GWAS, however, have only at best identi?ed moderate proportions of the genetic variants contributing to disease heritability. To provide cost-e?ective genotyping of common and rare variants to map the remaining heritability and to ?ne-map established loci, the Immunochip Consortium has developed a 200,000 SNP chip that has been produced in very large numbers for a fraction of the cost of GWAS chips. This chip provides a powerful tool for immunogenetics gene mapping. Common CNVs are an unlikely source of much missing heritability. Of the 95 loci known by SNP studies at the end of 2009 to be associated with Crohn’s disease and type 1 and type 2 diabetes, only three harbored CNVs that may explain the association [2]. In an extensive study of the role of CNVs in eight common diseases, the Wellcome Trust Case Control Consortium identi? ed just three CNV associations, each of which had already been identi? ed by tagSNP studie e study concluded Genomewide association studies (GWAS) have made a that ‘common CNVs which can be typed on existing phenomenal contribution to our understanding of platforms are unlikely to contribute greatly to the genetic common heritable diseases