Pervasive Sharing of Genetic Effects in Autoimmune Disease
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...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
Public Library of Science
2012
|
| Online Access: | http://hdl.handle.net/1721.1/69081 |
| _version_ | 1826208035934044160 |
|---|---|
| author | Cotsapas, Chris Voight, Benjamin F. Lage, Kasper Neale, Benjamin M. Wallace, Chris Abecasis, Gonçalo R. Barrett, Jeffrey C. Behrens, Timothy Cho, Judy Jager, Philip L. De Elder, James T. Graham, Robert R. Gregersen, Peter K. Klareskog, Lars Siminovitch, Katherine A. Heel, David A. van Wijmenga, Cisca Worthington, Jane Todd, John A. Hafler, David A. Rich, Stephen S. Daly, Mark J. Rossin, Elizabeth |
| author2 | Whitaker College of Health Sciences and Technology |
| author_facet | Whitaker College of Health Sciences and Technology Cotsapas, Chris Voight, Benjamin F. Lage, Kasper Neale, Benjamin M. Wallace, Chris Abecasis, Gonçalo R. Barrett, Jeffrey C. Behrens, Timothy Cho, Judy Jager, Philip L. De Elder, James T. Graham, Robert R. Gregersen, Peter K. Klareskog, Lars Siminovitch, Katherine A. Heel, David A. van Wijmenga, Cisca Worthington, Jane Todd, John A. Hafler, David A. Rich, Stephen S. Daly, Mark J. Rossin, Elizabeth |
| author_sort | Cotsapas, Chris |
| collection | MIT |
| description | 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 PCPMA<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. |
| first_indexed | 2024-09-23T13:59:23Z |
| format | Article |
| id | mit-1721.1/69081 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T13:59:23Z |
| publishDate | 2012 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | mit-1721.1/690812022-09-28T17:33:10Z Pervasive Sharing of Genetic Effects in Autoimmune Disease Cotsapas, Chris Voight, Benjamin F. Lage, Kasper Neale, Benjamin M. Wallace, Chris Abecasis, Gonçalo R. Barrett, Jeffrey C. Behrens, Timothy Cho, Judy Jager, Philip L. De Elder, James T. Graham, Robert R. Gregersen, Peter K. Klareskog, Lars Siminovitch, Katherine A. Heel, David A. van Wijmenga, Cisca Worthington, Jane Todd, John A. Hafler, David A. Rich, Stephen S. Daly, Mark J. Rossin, Elizabeth Whitaker College of Health Sciences and Technology Hafler, David A. Rossin, Elizabeth 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 PCPMA<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. 2012-02-10T17:40:25Z 2012-02-10T17:40:25Z 2011-08 2011-01 Article http://purl.org/eprint/type/JournalArticle 1553-7390 1553-7404 http://hdl.handle.net/1721.1/69081 Cotsapas, Chris et al. “Pervasive Sharing of Genetic Effects in Autoimmune Disease.” Ed. Emmanouil T. Dermitzakis. PLoS Genetics 7.8 (2011): e1002254. Web. 10 Feb. 2012. en_US http://dx.doi.org/10.1371/journal.pgen.1002254 PLoS Genetics Creative Commons Attribution http://creativecommons.org/licenses/by/2.5/ application/pdf Public Library of Science PLoS |
| spellingShingle | Cotsapas, Chris Voight, Benjamin F. Lage, Kasper Neale, Benjamin M. Wallace, Chris Abecasis, Gonçalo R. Barrett, Jeffrey C. Behrens, Timothy Cho, Judy Jager, Philip L. De Elder, James T. Graham, Robert R. Gregersen, Peter K. Klareskog, Lars Siminovitch, Katherine A. Heel, David A. van Wijmenga, Cisca Worthington, Jane Todd, John A. Hafler, David A. Rich, Stephen S. Daly, Mark J. Rossin, Elizabeth Pervasive Sharing of Genetic Effects in Autoimmune Disease |
| title | Pervasive Sharing of Genetic Effects in Autoimmune Disease |
| title_full | Pervasive Sharing of Genetic Effects in Autoimmune Disease |
| title_fullStr | Pervasive Sharing of Genetic Effects in Autoimmune Disease |
| title_full_unstemmed | Pervasive Sharing of Genetic Effects in Autoimmune Disease |
| title_short | Pervasive Sharing of Genetic Effects in Autoimmune Disease |
| title_sort | pervasive sharing of genetic effects in autoimmune disease |
| url | http://hdl.handle.net/1721.1/69081 |
| work_keys_str_mv | AT cotsapaschris pervasivesharingofgeneticeffectsinautoimmunedisease AT voightbenjaminf pervasivesharingofgeneticeffectsinautoimmunedisease AT lagekasper pervasivesharingofgeneticeffectsinautoimmunedisease AT nealebenjaminm pervasivesharingofgeneticeffectsinautoimmunedisease AT wallacechris pervasivesharingofgeneticeffectsinautoimmunedisease AT abecasisgoncalor pervasivesharingofgeneticeffectsinautoimmunedisease AT barrettjeffreyc pervasivesharingofgeneticeffectsinautoimmunedisease AT behrenstimothy pervasivesharingofgeneticeffectsinautoimmunedisease AT chojudy pervasivesharingofgeneticeffectsinautoimmunedisease AT jagerphiliplde pervasivesharingofgeneticeffectsinautoimmunedisease AT elderjamest pervasivesharingofgeneticeffectsinautoimmunedisease AT grahamrobertr pervasivesharingofgeneticeffectsinautoimmunedisease AT gregersenpeterk pervasivesharingofgeneticeffectsinautoimmunedisease AT klareskoglars pervasivesharingofgeneticeffectsinautoimmunedisease AT siminovitchkatherinea pervasivesharingofgeneticeffectsinautoimmunedisease AT heeldavidavan pervasivesharingofgeneticeffectsinautoimmunedisease AT wijmengacisca pervasivesharingofgeneticeffectsinautoimmunedisease AT worthingtonjane pervasivesharingofgeneticeffectsinautoimmunedisease AT toddjohna pervasivesharingofgeneticeffectsinautoimmunedisease AT haflerdavida pervasivesharingofgeneticeffectsinautoimmunedisease AT richstephens pervasivesharingofgeneticeffectsinautoimmunedisease AT dalymarkj pervasivesharingofgeneticeffectsinautoimmunedisease AT rossinelizabeth pervasivesharingofgeneticeffectsinautoimmunedisease |