Pervasive Sharing of Genetic Effects in Autoimmune Disease

Chris Cotsapas; Benjamin F. Voight; Elizabeth Rossin; Kasper Lage; Benjamin M. Neale; Chris Wallace; Goncalo R. Abecasis; Jeffrey C. Barrett; Timothy Behrens; Judy Cho; Philip L. De Jager; James T. Elder; Robert R. Graham; Peter Gregersen; Lars Klareskog; Katherine A. Siminovitch; David A. van Heel; Cisca Wijmenga; Jane Worthington; John A. Todd; David A. Hafler; Stephen S. Rich; Mark J. Daly; FOCiS Network Consortia

doi:10.1371/journal.pgen.1002254

Pervasive Sharing of Genetic Effects in Autoimmune Disease

Chris Cotsapas^*, Benjamin F. Voight, Elizabeth Rossin, Kasper Lage, Benjamin M. Neale, Chris Wallace, Goncalo R. Abecasis, Jeffrey C. Barrett, Timothy Behrens, Judy Cho, Philip L. De Jager, James T. Elder, Robert R. Graham, Peter Gregersen, Lars Klareskog, Katherine A. Siminovitch, David A. van Heel, Cisca Wijmenga, Jane Worthington, John A. ToddDavid A. Hafler, Stephen S. Rich, Mark J. Daly, FOCiS Network Consortia

^*Corresponding author for this work

Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI)

Research output: Contribution to journal › Article › Academic › peer-review

436 Citations (Scopus)

298 Downloads (Pure)

Abstract

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)

Original language	English
Article number	1002254
Number of pages	8
Journal	PLoS genetics
Volume	7
Issue number	8
DOIs	https://doi.org/10.1371/journal.pgen.1002254
Publication status	Published - 10-Aug-2011

Keywords

GENOME-WIDE ASSOCIATION
SYSTEMIC-LUPUS-ERYTHEMATOSUS
RHEUMATOID-ARTHRITIS
CELIAC-DISEASE
SUSCEPTIBILITY LOCI
RISK LOCI
VARIANTS
METAANALYSIS
REPLICATION
ALLELE

Access to Document

10.1371/journal.pgen.1002254Licence: CC BY

Pervasive Sharing of Genetic Effects in Autoimmune DiseaseFinal publisher's version, 207 KBLicence: CC BY

Handle.net

Persistent link

Cite this

Cotsapas, C., Voight, B. F., Rossin, E., Lage, K., Neale, B. M., Wallace, C., Abecasis, 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., ... FOCiS Network Consortia (2011). Pervasive Sharing of Genetic Effects in Autoimmune Disease. PLoS genetics, 7(8), Article 1002254. https://doi.org/10.1371/journal.pgen.1002254

@article{df1e2a8c7660402aba44dd10be55a099,

title = "Pervasive Sharing of Genetic Effects in Autoimmune Disease",

abstract = "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)",

keywords = "GENOME-WIDE ASSOCIATION, SYSTEMIC-LUPUS-ERYTHEMATOSUS, RHEUMATOID-ARTHRITIS, CELIAC-DISEASE, SUSCEPTIBILITY LOCI, RISK LOCI, VARIANTS, METAANALYSIS, REPLICATION, ALLELE",

author = "Chris Cotsapas and Voight, {Benjamin F.} and Elizabeth Rossin and Kasper Lage and Neale, {Benjamin M.} and Chris Wallace and Abecasis, {Goncalo R.} and Barrett, {Jeffrey C.} and Timothy Behrens and Judy Cho and {De Jager}, {Philip L.} and Elder, {James T.} and Graham, {Robert R.} and Peter Gregersen and Lars Klareskog and Siminovitch, {Katherine A.} and {van Heel}, {David A.} and Cisca Wijmenga and Jane Worthington and Todd, {John A.} and Hafler, {David A.} and Rich, {Stephen S.} and Daly, {Mark J.} and {FOCiS Network Consortia}",

year = "2011",

month = aug,

day = "10",

doi = "10.1371/journal.pgen.1002254",

language = "English",

volume = "7",

journal = "PLoS genetics",

issn = "1553-7390",

publisher = "PUBLIC LIBRARY SCIENCE",

number = "8",

}

Cotsapas, C, Voight, BF, Rossin, E, Lage, K, Neale, BM, Wallace, C, Abecasis, GR, Barrett, JC, Behrens, T, Cho, J, De Jager, PL, Elder, JT, Graham, RR, Gregersen, P, Klareskog, L, Siminovitch, KA, van Heel, DA, Wijmenga, C, Worthington, J, Todd, JA, Hafler, DA, Rich, SS, Daly, MJ & FOCiS Network Consortia 2011, 'Pervasive Sharing of Genetic Effects in Autoimmune Disease', PLoS genetics, vol. 7, no. 8, 1002254. https://doi.org/10.1371/journal.pgen.1002254

TY - JOUR

T1 - Pervasive Sharing of Genetic Effects in Autoimmune Disease

AU - Cotsapas, Chris

AU - Voight, Benjamin F.

AU - Rossin, Elizabeth

AU - Lage, Kasper

AU - Neale, Benjamin M.

AU - Wallace, Chris

AU - Abecasis, Goncalo R.

AU - Barrett, Jeffrey C.

AU - Behrens, Timothy

AU - Cho, Judy

AU - De Jager, Philip L.

AU - Elder, James T.

AU - Graham, Robert R.

AU - Gregersen, Peter

AU - Klareskog, Lars

AU - Siminovitch, Katherine A.

AU - van Heel, David A.

AU - Wijmenga, Cisca

AU - Worthington, Jane

AU - Todd, John A.

AU - Hafler, David A.

AU - Rich, Stephen S.

AU - Daly, Mark J.

AU - FOCiS Network Consortia

PY - 2011/8/10

Y1 - 2011/8/10

N2 - 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)

AB - 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)

KW - GENOME-WIDE ASSOCIATION

KW - SYSTEMIC-LUPUS-ERYTHEMATOSUS

KW - RHEUMATOID-ARTHRITIS

KW - CELIAC-DISEASE

KW - SUSCEPTIBILITY LOCI

KW - RISK LOCI

KW - VARIANTS

KW - METAANALYSIS

KW - REPLICATION

KW - ALLELE

U2 - 10.1371/journal.pgen.1002254

DO - 10.1371/journal.pgen.1002254

M3 - Article

SN - 1553-7390

VL - 7

JO - PLoS genetics

JF - PLoS genetics

IS - 8

M1 - 1002254

ER -

Pervasive Sharing of Genetic Effects in Autoimmune Disease

Abstract

Keywords

Access to Document

Handle.net

Fingerprint

Cite this