ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1639

GWAS In Hispanic and Latin American Individuals Enriched For Amerindian Ancestry Identifies a New Locus Associated With Systemic Lupus Erythematosus

Marta Eugenia Alarcon Riquelme1, Julie T. Ziegler2, Mary E. Comeau3, Elena Sanchez4, Bernado Pons-Estel5, Eduardo Acevedo6, Jorge Mariano Cucho6, Ignacio Garcia de la Torre7, Mario H. Cardiel8, Pedro Miranda9, Luis Cattogio10, Marco Maradiaga11, Jorge Esquivel-Valerio12, Jose F Moctezuma13, Mercedes Garcia14, Guillermo Berbotto15, Alejandra Babini16, Hugo Scherbarth17, Sergio Toloza18, Judith A James19, Teresa Tusie-Luna20, John B Harley21, Raphael Zidovetski22, Carl Langefeldt2 and Chaim O. Jacob23, 1Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK, 2Wake Forest School of Medicine, Winston-Salem, NC, 3Wake Forest University Health Sciences, Winston-Salem, NC, 4King's College London, London, United Kingdom, 5Hospital Provincial de Rosario, Rosario, Argentina, 6Hospital Nacional Guillermo Almenara Irigoyen, Lima, Peru, 7Hospital General de Occidente, Zapopan, Mexico, 8Centro de Investigacion Clinica de Morelia, Morelia, Mexico, 9Universidad de Chile and Centro de Estudios Reumatologicos, Santiago de Chile, Chile, 10Hospital Italiano, Buenos Aires, Argentina, 11Hospital General de Culiacán, Culiacan, Sinaloa, Mexico, 12Hospital Universitario Dr. José Eleuterio González, Universidad Autonoma de Nuevo León, Nuevo Leon, Mexico, 13Hospital General de Mexico, Mexico, Mexico, 14Hospital San Martin, La Plata, Argentina, 15Hospital Eva Peron, Granadero Baigorria, Argentina, 16Hospital Privado de Cordoba, Cordoba, Argentina, 17H.I.G.A. Oscar E. Alende, Mar del Plata, Argentina, 18Hospital San Juan Bautista, Catamarca, Argentina, 19Oklahoma Medical Research Foundation, Oklahoma City, OK, 20Instituto de Investigaciones Biomédicas de la Universidad Nacional Autónoma de México, and Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico, Mexico, 21Childrens Hospital, Cincinnati, OH, 22University of Southern California, Los Angeles, CA, 23Division of Rheumatology, University of Southern California Keck School of Medicine, Los Angeles, CA

Meeting: 2013 ACR/ARHP Annual Meeting

Keywords: , , ,

Session Information

Title: Systemic Lupus Erythematosus-Human Etiology and Pathogenesis: Genetics and Genomics

Session Type: Abstract Submissions (ACR)

Background/Purpose:

Systemic lupus erythematosus (SLE), a chronic autoimmune disease with a strong genetic component, exhibits a 9:1 female to male ratio and disproportionate impact on individuals of admixed ancestries in the Americas. We performed a genome-wide association scan on individuals from Latin America and the United States enriched for Amerindian while admixed with European ancestry.

Methods: A total of 4516 individuals were genotyped, 2906 for the Illumina Human Quadv1 (OMNI1) and data from1610 out-of-study controls for the OMNI2.5 Bead array was obtained yielding, 996,672 SNPs for final analysis (580,483 SNP were on both BeadArrays). After quality control filters were applied, a total of 3710 individuals were kept for genetic association analysis. The final inflation factor was 1.00 using the 2 first principal components (PC). Principal component analysis revealed 2 differentiated populations that corresponded to a South American (individuals from Argentina, Chile and Peru; N = 875), and a North American group composed of individuals from Mexico, and Hispanics and Native Americans from the United States (N = 2835). SNP-SLE association was tested using logistic regression model adjusting for PC. Results for the additive model are reported.

Results:  One novel genetic association was identified in chromosome 10, between INA, USMG5 and PDCD11 (rs4917385, Pvalue = 7.48 x 10-8, min FDR p-value=0.00099, OR=0.75, CI=0.67-0.84). Several known lupus susceptibility loci were replicated. Overall, the strongest effect was that of TNPO3-IRF5 locus, followed by the HLA class II region. Regions previously associated in Europeans that were associated for the first time in individuals with enriched Amerindian ancestry were TNFSF4, NCF2, NMNAT2, JAZF1, FAM167A-BLK, and PTTG1–MiR146a. Regions previously associated in Asians and associated for the first time in individuals with enriched Amerindian ancestry were SLC15A4 and WDFY4.

Conclusion: We identify a new locus for SLE in chromosome 10. Our data show the major importance of genes outside the HLA in the susceptibility for lupus in this population and provide support for loci previously found in Asians and Europeans

Disclosure:

M. E. Alarcon Riquelme,
None;

J. T. Ziegler,
None;

M. E. Comeau,
None;

E. Sanchez,
None;

B. Pons-Estel,

Abbott Laboratories,

2;

E. Acevedo,
None;

J. M. Cucho,
None;

I. Garcia de la Torre,
None;

M. H. Cardiel,
None;

P. Miranda,

Janssen, HGS, Medimmune,Celltrion, Sanofi, Roche, Pfizer, and MSD,

9,

Pfizer Inc,

9;

L. Cattogio,
None;

M. Maradiaga,
None;

J. Esquivel-Valerio,
None;

J. F. Moctezuma,
None;

M. Garcia,
None;

G. Berbotto,
None;

A. Babini,
None;

H. Scherbarth,
None;

S. Toloza,
None;

J. A. James,
None;

T. Tusie-Luna,
None;

J. B. Harley,
None;

R. Zidovetski,
None;

C. Langefeldt,
None;

C. O. Jacob,
None.

« Back to 2013 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/gwas-in-hispanic-and-latin-american-individuals-enriched-for-amerindian-ancestry-identifies-a-new-locus-associated-with-systemic-lupus-erythematosus/