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Pervasive sharing of genetic effects in autoimmune disease
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نویسنده
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cotsapas c. ,voight b.f. ,rossin e. ,lage k. ,neale b.m. ,wallace c. ,abecasisgonç g.r. ,barrett j.c. ,behrens t. ,cho j. ,de jager p.l. ,elder j.t. ,graham r.r. ,gregersen p. ,klareskog l. ,siminovitch k.a. ,van heel d.a. ,wijmenga c. ,worthington j. ,todd j.a. ,hafler d.a. ,rich s.s. ,daly m.j.
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منبع
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plos genetics - 2011 - دوره : 7 - شماره : 8
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چکیده
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Genome-wide association (gwa) studies have identified 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. in this work we evaluate 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. we 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,we find evidence that 47/107 (44%) immune-mediated disease risk snps are associated to multiple-but not all-immune-mediated diseases (snp-wise p cpma<0.01). we also show that distinct groups of interacting proteins are encoded near snps which predispose to the same subsets of diseases; we propose these as the mechanistic basis of shared disease risk. we are thus able to leverage genetic data across diseases to construct biological hypotheses about the underlying mechanism of pathogenesis. © 2011 cotsapas et al.
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آدرس
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center for human genetic research,massachusetts general hospital,boston,ma,united states,medical and population genetics,broad institute of mit and harvard,cambridge,ma,united states,department of medicine,harvard medical school,boston,ma,united states,department of neurology,yale university school of medicine,new haven,ct,united states,department of genetics,yale university school of medicine,new haven,ct, United States, center for human genetic research,massachusetts general hospital,boston,ma,united states,medical and population genetics,broad institute of mit and harvard,cambridge,ma,united states,department of medicine,harvard medical school,boston,ma, United States, center for human genetic research,massachusetts general hospital,boston,ma,united states,medical and population genetics,broad institute of mit and harvard,cambridge,ma,united states,department of medicine,harvard medical school,boston,ma,united states,health science and technology md program,harvard university and massachusetts institute of technology,boston,ma,united states,harvard biological and biomedical sciences program,harvard university,boston,ma, United States, medical and population genetics,broad institute of mit and harvard,cambridge,ma,united states,pediatric surgical research laboratories,massachusetts general hospital,boston,ma,united states,center for biological sequence analysis,department of systems biology,technical university of denmark,lyngby, Denmark, center for human genetic research,massachusetts general hospital,boston,ma,united states,medical and population genetics,broad institute of mit and harvard,cambridge,ma,united states,department of medicine,harvard medical school,boston,ma,united states,analytical and translational genetics unity,massachusetts general hospital,boston,ma, United States, juvenile diabetes research foundation/wellcome trust diabetes and inflammation laboratory,department of medical genetics,cambridge institute for medical research,university of cambridge,cambridge, United Kingdom, center for statistical genetics,university of michigan,ann arbor,ma, United States, human genetics,wellcome trust sanger institute,cambridge, United Kingdom, genentech,south san francisco,ca, United States, department of genetics,yale university school of medicine,new haven,ct,united states,departments of medicine and genetics,yale university school of medicine,new haven,ct, United States, department of medicine,harvard medical school,boston,ma,united states,department of neurology,brigham and women's hospital,boston,ma, United States, department of dermatology,university of michigan,ann arbor,mi, United States, genentech,south san francisco,ca, United States, feinstein institute for medical research,north shore-long island jewish health system,manhasset,ny, United States, rheumatology unit,department of medicine,karolinska institutet,stockholm, Sweden, samuel lunenfeld research institute,mount sinai hospital,toronto, Canada, blizard institute,the london school of medicine and dentistry,london, United Kingdom, department of genetics,university medical center groningen and groningen university,groningen, Netherlands, arthritis research uk epidemiology unit,school of translational medicine,manchester academic health sciences centre,university of manchester,manchester, United Kingdom, juvenile diabetes research foundation/wellcome trust diabetes and inflammation laboratory,department of medical genetics,cambridge institute for medical research,university of cambridge,cambridge, United Kingdom, department of neurology,yale university school of medicine,new haven,ct, United States, center for public health genomics,university of virginia,charlottesville,va, United States, center for human genetic research,massachusetts general hospital,boston,ma,united states,medical and population genetics,broad institute of mit and harvard,cambridge,ma,united states,department of medicine,harvard medical school,boston,ma,united states,analytical and translational genetics unity,massachusetts general hospital,boston,ma, United States
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Authors
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