A systemic sclerosis and systemic lupus erythematosus pan-meta-GWAS reveals new shared susceptibility loci

J.E. Martin; S. Assassi; L.M. Diaz-Gallo; J.C.A. dr. Broen; C.P. Simeon; I. Castellvi; E. Vicente-Rabaneda; V. Fonollosa; N. Ortego-Centeno; M.A. Gonzalez-Gay; G. Espinosa; P. Carreira; x Spanish Scleroderma Group34; M. Camps; J.M. Sabio; S. D'alfonso; M.C. Vonk; A.E. Voskuyl; A.J. Schuerwegh; A. Kreuter; T. Witte; G. Riemekasten; N. Hunzelmann; P. Airo; L. Beretta; X et al; B.P.C. Koeleman; T.R.D.J. Radstake; J. Martin

doi:10.1093/hmg/ddt248

A systemic sclerosis and systemic lupus erythematosus pan-meta-GWAS reveals new shared susceptibility loci

J.E. Martin, S. Assassi, L.M. Diaz-Gallo, J.C.A. dr. Broen, C.P. Simeon, I. Castellvi, E. Vicente-Rabaneda, V. Fonollosa, N. Ortego-Centeno, M.A. Gonzalez-Gay, G. Espinosa, P. Carreira, x Spanish Scleroderma Group34, M. Camps, J.M. Sabio, S. D'alfonso, M.C. Vonk, A.E. Voskuyl, A.J. Schuerwegh, A. KreuterT. Witte, G. Riemekasten, N. Hunzelmann, P. Airo, L. Beretta, X et al, B.P.C. Koeleman, T.R.D.J. Radstake, J. Martin

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

Abstract

Systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) are two archetypal systemic autoimmune diseases which have been shown to share multiple genetic susceptibility loci. In order to gain insight into the genetic basis of these diseases, we performed a pan-meta-analysis of two genome-wide association studies (GWASs) together with a replication stage including additional SSc and SLE cohorts. This increased the sample size to a total of 21 109 (6835 cases and 14 274 controls). We selected for replication 19 SNPs from the GWAS data. We were able to validate KIAA0319L (P = 3.31 x 10(-11), OR = 1.49) as novel susceptibility loci for SSc and SLE. Furthermore, we also determined that the previously described SLE susceptibility loci PXK (P = 3.27 x 10(-11), OR = 1.20) and JAZF1 (P = 1.11 x 10(-8), OR = 1.13) are shared with SSc. Supporting these new discoveries, we observed that KIAA0319L was overexpressed in peripheral blood cells of SSc and SLE patients compared with healthy controls. With these, we add three (KIAA0319L, PXK and JAZF1) and one (KIAA0319L) new susceptibility loci for SSc and SLE, respectively, increasing significantly the knowledge of the genetic basis of autoimmunity.

Original language	English
Pages (from-to)	4021-4029
Number of pages	9
Journal	Human Molecular Genetics
Volume	22
Issue number	19
DOIs	https://doi.org/10.1093/hmg/ddt248
Publication status	Published - 2013

Keywords

GENOME-WIDE ASSOCIATION
ADHESION MOLECULES
CELL-ADHESION
DISEASE
CLASSIFICATION
POPULATION
RISK
PXK
REPLICATION
VARIANTS

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10.1093/hmg/ddt248

http://www.ncbi.nlm.nih.gov/pubmed/?term=23740937

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Martin, J. E., Assassi, S., Diaz-Gallo, L. M., dr. Broen, J. C. A., Simeon, C. P., Castellvi, I., Vicente-Rabaneda, E., Fonollosa, V., Ortego-Centeno, N., Gonzalez-Gay, M. A., Espinosa, G., Carreira, P., Spanish Scleroderma Group34, X., Camps, M., Sabio, J. M., D'alfonso, S., Vonk, M. C., Voskuyl, A. E., Schuerwegh, A. J., ... Martin, J. (2013). A systemic sclerosis and systemic lupus erythematosus pan-meta-GWAS reveals new shared susceptibility loci. Human Molecular Genetics, 22(19), 4021-4029. https://doi.org/10.1093/hmg/ddt248

@article{2cdfd4b3114f45b5841bab0c22778288,

title = "A systemic sclerosis and systemic lupus erythematosus pan-meta-GWAS reveals new shared susceptibility loci",

abstract = "Systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) are two archetypal systemic autoimmune diseases which have been shown to share multiple genetic susceptibility loci. In order to gain insight into the genetic basis of these diseases, we performed a pan-meta-analysis of two genome-wide association studies (GWASs) together with a replication stage including additional SSc and SLE cohorts. This increased the sample size to a total of 21 109 (6835 cases and 14 274 controls). We selected for replication 19 SNPs from the GWAS data. We were able to validate KIAA0319L (P = 3.31 x 10(-11), OR = 1.49) as novel susceptibility loci for SSc and SLE. Furthermore, we also determined that the previously described SLE susceptibility loci PXK (P = 3.27 x 10(-11), OR = 1.20) and JAZF1 (P = 1.11 x 10(-8), OR = 1.13) are shared with SSc. Supporting these new discoveries, we observed that KIAA0319L was overexpressed in peripheral blood cells of SSc and SLE patients compared with healthy controls. With these, we add three (KIAA0319L, PXK and JAZF1) and one (KIAA0319L) new susceptibility loci for SSc and SLE, respectively, increasing significantly the knowledge of the genetic basis of autoimmunity.",

keywords = "GENOME-WIDE ASSOCIATION, ADHESION MOLECULES, CELL-ADHESION, DISEASE, CLASSIFICATION, POPULATION, RISK, PXK, REPLICATION, VARIANTS",

author = "J.E. Martin and S. Assassi and L.M. Diaz-Gallo and {dr. Broen}, J.C.A. and C.P. Simeon and I. Castellvi and E. Vicente-Rabaneda and V. Fonollosa and N. Ortego-Centeno and M.A. Gonzalez-Gay and G. Espinosa and P. Carreira and {Spanish Scleroderma Group34}, x and M. Camps and J.M. Sabio and S. D'alfonso and M.C. Vonk and A.E. Voskuyl and A.J. Schuerwegh and A. Kreuter and T. Witte and G. Riemekasten and N. Hunzelmann and P. Airo and L. Beretta and {et al}, X and B.P.C. Koeleman and T.R.D.J. Radstake and J. Martin",

year = "2013",

doi = "10.1093/hmg/ddt248",

language = "English",

volume = "22",

pages = "4021--4029",

journal = "Human Molecular Genetics",

issn = "0964-6906",

publisher = "Oxford University Press",

number = "19",

}

Martin, JE, Assassi, S, Diaz-Gallo, LM, dr. Broen, JCA, Simeon, CP, Castellvi, I, Vicente-Rabaneda, E, Fonollosa, V, Ortego-Centeno, N, Gonzalez-Gay, MA, Espinosa, G, Carreira, P, Spanish Scleroderma Group34, X, Camps, M, Sabio, JM, D'alfonso, S, Vonk, MC, Voskuyl, AE, Schuerwegh, AJ, Kreuter, A, Witte, T, Riemekasten, G, Hunzelmann, N, Airo, P, Beretta, L, et al, X, Koeleman, BPC, Radstake, TRDJ & Martin, J 2013, 'A systemic sclerosis and systemic lupus erythematosus pan-meta-GWAS reveals new shared susceptibility loci', Human Molecular Genetics, vol. 22, no. 19, pp. 4021-4029. https://doi.org/10.1093/hmg/ddt248

TY - JOUR

T1 - A systemic sclerosis and systemic lupus erythematosus pan-meta-GWAS reveals new shared susceptibility loci

AU - Martin, J.E.

AU - Assassi, S.

AU - Diaz-Gallo, L.M.

AU - dr. Broen, J.C.A.

AU - Simeon, C.P.

AU - Castellvi, I.

AU - Vicente-Rabaneda, E.

AU - Fonollosa, V.

AU - Ortego-Centeno, N.

AU - Gonzalez-Gay, M.A.

AU - Espinosa, G.

AU - Carreira, P.

AU - Spanish Scleroderma Group34, x

AU - Camps, M.

AU - Sabio, J.M.

AU - D'alfonso, S.

AU - Vonk, M.C.

AU - Voskuyl, A.E.

AU - Schuerwegh, A.J.

AU - Kreuter, A.

AU - Witte, T.

AU - Riemekasten, G.

AU - Hunzelmann, N.

AU - Airo, P.

AU - Beretta, L.

AU - et al, X

AU - Koeleman, B.P.C.

AU - Radstake, T.R.D.J.

AU - Martin, J.

PY - 2013

Y1 - 2013

N2 - Systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) are two archetypal systemic autoimmune diseases which have been shown to share multiple genetic susceptibility loci. In order to gain insight into the genetic basis of these diseases, we performed a pan-meta-analysis of two genome-wide association studies (GWASs) together with a replication stage including additional SSc and SLE cohorts. This increased the sample size to a total of 21 109 (6835 cases and 14 274 controls). We selected for replication 19 SNPs from the GWAS data. We were able to validate KIAA0319L (P = 3.31 x 10(-11), OR = 1.49) as novel susceptibility loci for SSc and SLE. Furthermore, we also determined that the previously described SLE susceptibility loci PXK (P = 3.27 x 10(-11), OR = 1.20) and JAZF1 (P = 1.11 x 10(-8), OR = 1.13) are shared with SSc. Supporting these new discoveries, we observed that KIAA0319L was overexpressed in peripheral blood cells of SSc and SLE patients compared with healthy controls. With these, we add three (KIAA0319L, PXK and JAZF1) and one (KIAA0319L) new susceptibility loci for SSc and SLE, respectively, increasing significantly the knowledge of the genetic basis of autoimmunity.

AB - Systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) are two archetypal systemic autoimmune diseases which have been shown to share multiple genetic susceptibility loci. In order to gain insight into the genetic basis of these diseases, we performed a pan-meta-analysis of two genome-wide association studies (GWASs) together with a replication stage including additional SSc and SLE cohorts. This increased the sample size to a total of 21 109 (6835 cases and 14 274 controls). We selected for replication 19 SNPs from the GWAS data. We were able to validate KIAA0319L (P = 3.31 x 10(-11), OR = 1.49) as novel susceptibility loci for SSc and SLE. Furthermore, we also determined that the previously described SLE susceptibility loci PXK (P = 3.27 x 10(-11), OR = 1.20) and JAZF1 (P = 1.11 x 10(-8), OR = 1.13) are shared with SSc. Supporting these new discoveries, we observed that KIAA0319L was overexpressed in peripheral blood cells of SSc and SLE patients compared with healthy controls. With these, we add three (KIAA0319L, PXK and JAZF1) and one (KIAA0319L) new susceptibility loci for SSc and SLE, respectively, increasing significantly the knowledge of the genetic basis of autoimmunity.

KW - GENOME-WIDE ASSOCIATION

KW - ADHESION MOLECULES

KW - CELL-ADHESION

KW - DISEASE

KW - CLASSIFICATION

KW - POPULATION

KW - RISK

KW - PXK

KW - REPLICATION

KW - VARIANTS

U2 - 10.1093/hmg/ddt248

DO - 10.1093/hmg/ddt248

M3 - Article

C2 - 23740937

SN - 0964-6906

VL - 22

SP - 4021

EP - 4029

JO - Human Molecular Genetics

JF - Human Molecular Genetics

IS - 19

ER -

A systemic sclerosis and systemic lupus erythematosus pan-meta-GWAS reveals new shared susceptibility loci

Abstract

Keywords

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