ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 980

Genomewide Association Study in Systemic Lupus Erythematosus: Known Loci

Antonio Fernandez-Nebro1, Patricia E. Carreira2, Ricardo Blanco3, Victor M. Martinez-Taboada4, Luis Carreño5, Alejandro Olive6, José Luis Andreu7, Mª Angeles Aguirre8, Paloma Vela9, Jose Javier Pérez Venegas10, Jose Luís Marenco11, Joan Miquel Nolla12, Antonio Zea13, José M. Pego-Reigosa14, Mercedes Freire González15, Gabriela Ávila16, María América López-Lasanta16, Raül Tortosa16, Antonio Julià16 and Sara Marsal16, 1Rheumatology, Hospital Regional Universitario Carlos Haya, Málaga, Spain, 2Rheumatology, Instituto de Investigación Hospital 12 de Octubre, Madrid, Spain, 3Rheumatology, Hospital Universitario Marques De Valdecilla, Santander, Spain, 4Rheumatology, Hospital Universitario Marques de Valdecilla. IFIMAV, Santander, Spain, 5Rheumatology, Gregorio Marañón Hospital, Madrid, Spain, 6Rheumatology Service, Germans Trias Pujol Hospital, Barcelona, Spain, 7Rheumatology, Puerta de Hierro Universitary Hospital, Madrid, Spain, 8Rheumatology, IMIBIC-Reina Sofia Hospital, Cordoba, Spain, 9Rheumatology, Hospital General Universitario de Alicante, Alicante, Spain, 10Rheumatology, Hospital del SAS de Jerez de la Frontera, Jerez De La Frontera, Spain, 11Rheumatology, HU Puerta de Hierro Majadahonda, Madrid, Spain, 12Rheumatology, Hospital Universitario de Bellvitge, Barcelona, Spain, 13Rheumatology, Hospital Universitario Ramon y Cajal, Madrid, Spain, 14Rheumatology, Hospital do Meixoeiro, Vigo, Spain, 15Rheumatology, Complejo Hospitalario Universitario de La Coruña,, La Coruña, Spain, 16Rheumatology Research Group, Vall d'Hebron Hospital Research Institute, Barcelona, Spain

Meeting: 2012 ACR/ARHP Annual Meeting

Keywords: ,

Session Information

Title: Genetics and Genomics of Rheumatic Diseases

Session Type: Abstract Submissions (ACR)

Background/Purpose: Systemic Lupus Erythematosus (SLE) is a complex autoimmune disease with an estimated prevalence of 40:100,000 cases in European populations. SLE has a strong genetic risk component (sibling relative risk ~30). Positional candidate studies have identified the association of HLADRB1, STAT4 and IRF5 loci with SLE risk. However, Genome-Wide Association Studies (GWAS) have allowed to expand the number of SLE risk loci to more than 20. In order to identify additional risk loci we have performed a GWAS in a Southern European population.

Methods: 510 SLE cases and 1,540 controls of Spanish origin were genotyped for more than 550,000 SNPs using Illumina Quad-610 platform. Only SNPs having >95% call rate and individuals having 95% of SNPs genotyped were included. Principal Component Analysis was used to identify the main axis of variation and discard any population outlier. After QC-filtering 489 SLE cases and 1490 Controls were included to test for association. In order to evaluate the association of all previously known SLE-risk loci all GWASs published from 2,008 to 2,012 where evaluated. Loci associated at a nominal P-value < 5e-5 were included. Within each SLE risk locus (n=43), the SNP having the highest statistical evidence was selected. For those SNPs not directly genotyped (n=3) genotype was imputed using MACH v1.0 software.

Results: From the 24 loci previously showing Genome-Wide level of association (P<5e-8) with SLE risk, loci HLA-DRB1, ITGAM, STAT4 and MSH5 were also replicated at Genome-Wide level. Four additional loci were also replicated at nominal (P<0.05) level of significance. From the remaining 19 loci still requiring additional evidence (5e-8 < P < 5 e-5) we were able to nominally replicate three loci. 20 SNPs within genomic regions previously not associated with SLE were also identified (P<5e-5).

Conclusion:  The present study has validated previous SLE risk loci in an independent population and gives additional support to loci with suggestive association. The association of the new candidate risk loci for SLE identified in this GWAS is currently being tested for validation.

Disclosure:

A. Fernandez-Nebro,
None;

P. E. Carreira,
None;

R. Blanco,
None;

V. M. Martinez-Taboada,
None;

L. Carreño,
None;

A. Olive,
None;

J. L. Andreu,
None;

M. A. Aguirre,
None;

P. Vela,
None;

J. J. Pérez Venegas,
None;

J. L. Marenco,
None;

J. M. Nolla,
None;

A. Zea,
None;

J. M. Pego-Reigosa,
None;

M. Freire González,
None;

G. Ávila,
None;

M. A. López-Lasanta,
None;

R. Tortosa,
None;

A. Julià,
None;

S. Marsal,
None.

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