To promote consortia involved in patient collections, and allow the exchange of ideas around new technologies, databases and analytical tools.
FOCIS created the Network of Consortia (NOC) to bring together disease-specific consortia for cross-disciplinary meetings and to provide assistance to interface with the NIH and industry to promote the goals of ascertaining the molecular pathology of human disease. NOC leveraged the new scientific platforms at the time to define the molecular pathology of human inflammatory disease.
The combined efforts of the NOC resulted in identifying numerous, replicable, genetic associations between common single nucleotide polymorphisms (SNPs) and risk of common autoimmune and inflammatory (immune-mediated) diseases, some of which are shared between two diseases. Along with epidemiological and clinical evidence, this suggests that some genetic risk factors may be shared across diseases—as is the case with alleles in the Major Histocompatibility Locus. The NOC has evaluated the extent of this sharing for 107 immune disease-risk SNPs in seven diseases: celiac disease, Crohn's disease, multiple sclerosis, psoriasis, rheumatoid arthritis, systemic lupus erythematosus, and type 1 diabetes and have developed a novel statistic for Cross Phenotype Meta-Analysis (CPMA) which detects association of a SNP to multiple, but not necessarily all, phenotypes. With it, there is evidence that 47/107 (44%) immune-mediated disease risk SNPs are associated to multiple immune-mediated diseases (SNP-wise PCPMA<0.01). It also shows that distinct groups of interacting proteins are encoded near SNPs which predispose to the same subsets of diseases; indicating these as the mechanistic basis of shared disease risk. The NOC is thus able to leverage genetic data across diseases to construct biological hypotheses about the underlying mechanism of pathogenesis. (Cotsapas C, Voight BF, Rossin E, Lage K, Neale BM, et al. (2011) Pervasive Sharing of Genetic Effects in Autoimmune Disease. PLoS Genet 7(8): e1002254. doi:10.1371/journal.pgen.1002254)
|Inflammatory Bowel Disease||Judy Cho, Yale University|
|Multiple Sclerosis, Genetics||Adrian Ivinson, Harvard|
|ITN: MS, Diabetes and T cell||Vicki Seyfert-Margolis, Immune Tolerance Network|
|Systemic Lupus Erythematosus Genetics||John Harley, Oklahoma Medical Research Foundation|
|Type 1 Diabetes, Genetics||Steve Rich, University of Virginia|
|Juvenile RA||David Glass, Cincinnati Children’s Hospital|
|North American RA||Peter Gregersen, Feinstein Institute for Medical Research|
|Wellcome Trust Case Control Consortium||Lon Cardon, Fred Hutchinson Cancer Research Center|
|Swedish Rheumatoid Arthritis Consortium||Mark Seielstad, Genome Institute – Singapore|
|IMAGEN Consortium||John Rioux, University of Montreal|
2009 NOC Meeting
The FOCIS Network of Consortia (NOC) met June 11 at FOCIS 2009 in San Francisco, California to discuss “Commonalities in Autoimmunity: Genomics and Beyond”. The session presented four general areas of discussion – the current status of the genetic basis of autoimmunity based upon data contributed to FOCIS/NOC by groups performing genome-wide association scans of individual autoimmune diseases (Cotsapas, Broad Institute), updates of genome-wide association scans in autoimmunity (Rich, De Jager, Vyse, Behrens, Xavier), new technologies for future genomic studies (Harkins, Stone), and correlating genotype with phenotype (Hafler, Xavier).
There were numerous examples of regions in the genome that appear to contribute to multiple autoimmune diseases, although the variants within the loci are not resolved and much research needs to be conducted to determine the number of variants in these loci that contribute to disease risk and whether the same variants (or different variants in the same locus) contribute to multiple diseases. The evolving technologies for fine mapping regions and high throughput (next generation) sequencing provide promise of better defining genetic risk. At the same time, it is becoming evident that the transition from genetic risk to clinical phenotype will require close collaboration between geneticists, immunologists, bioinformaticists, and clinical investigators as novel pathways and therapeutic targets emerge.
The future of the FOCIS NOC will continue to evolve from genome-wide association scans for autoimmune diseases into gene discovery and gene function. Two general areas of direction will be in focused medical resequencing of candidate genes/regions implicated in autoimmunity. An effort is already underway that is jointly sponsored by the FOCIS NOC, the Type 1 Diabetes Genetics Consortium and Roche 454. This research is sequencing regions in the human MHC, including HLA-D region variants that previously have not been characterized. A second area relates to the integration of genotype and phenotype characterization of autoimmune disease. As shown in the NOC session, there are multiple genes and pathways that shed light on disease process in Crohn’s disease and multiple sclerosis. With the FOCIS support of networks centered on immunophenotyping, a parallel and complementary genomic characterization of samples could add to our understanding of autoimmunity. Thus, the future of the NOC will be in greater dissection of the genomic contribution to autoimmune disease, and the transition of understanding the phenotypic outcome of genetic variation.
2008 NOC Meeting
The Federation of Clinical Immunology Societies (FOCIS) connects multiple disease specific, genetic consortia under the FOCIS Network of Consortia in an effort to uncover the genetic basis of autoimmunity. The Network, spearheaded by FOCIS Past-President, David Hafler, MD, Harvard University and Stephen Rich, PhD, University of Virginia, recently completed genome wide association scans revealing novel candidate genes that may provide important insights into disease pathogenesis and therapeutic targets.
The results were presented for the first time on June 11, 2007 at the Federation’s Annual Meeting (FOCIS 2007) in San Diego. The NOC unites again on June 9 at FOCIS 2008 in Boston to present reports from additional consortia who have completed their scans and have new data to share.
FOCIS 2008 – June 5-9, 2008
Network of Consortia Presentations – June 9
Boston Marriott Copley Place – Boston, Massachusetts, USA
"Scientists that once worked in disease-specific silos are uniting to create a catalogue of common genetic variations that will enable scientists to unravel underlying causes of autoimmune diseases," said Stephen Rich. “New data across diseases is showing great commonality, identifying potential targets that work across autoimmune diseases,” he added.
The Federation of Clinical Immunology Societies (FOCIS) has taken on the role of connecting multiple disease specific, genetic consortia under the FOCIS Network of Consortia in an effort to uncover the genetic basis of autoimmunity. The Network, spearheaded by FOCIS President, David Hafler, MD, Harvard University and Stephen Rich, PhD, University of Virginia, has recently completed genome wide association scans revealing novel candidate genes that may provide important insights into disease pathogenesis and therapeutic targets.
The results were presented for the first time on June 11 at the Federation’s Annual Meeting (FOCIS 2007) in San Diego.
Francis Collins, MD, PhD of the National Human Genome Research Institute presented a cross-section of data from ongoing genome wide association scans in autoimmune disease – inflammatory bowel disease (IBD), juvenile idiopathic arthritis (JIA), multiple sclerosis (MS), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and type 1 diabetes (T1D). In addition, the Wellcome Trust Case Control Consortium (WTCCC) presented a series of disease-oriented genome wide association scans using a common control group.
“Scientists that once worked in disease-specific silos are uniting to create a catalogue of common genetic variations that will enable scientists to unravel underlying causes of autoimmune diseases,” said Stephen Rich. “New data across diseases is showing great commonality, identifying potential targets that work across autoimmune diseases,” he added.