Identification of a systemic lupus erythematosus susceptibility locus at 11p13 between PDHX and CD44 in a multiethnic study

Christopher J. Lessard, Indra Adrianto, Jennifer A. Kelly, Kenneth M. Kaufman, Kiely M. Grundahl, Adam Adler, Adrienne H. Williams, Caroline J. Gallant, Juan Manuel Anaya, Sang Cheol Bae, Susan A. Boackle, Elizabeth E. Brown, Deh Ming Chang, Lindsey A. Criswell, Jeffrey C. Edberg, Barry I. Freedman, Peter K. Gregersen, Gary S. Gilkeson, Chaim O. Jacob, Judith A. JamesDiane L. Kamen, Robert P. Kimberly, Javier Martin, Joan T. Merrill, Timothy B. Niewold, So Yeon Park, Michelle A. Petri, Bernardo A. Pons-Estel, Rosalind Ramsey-Goldman, John D. Reveille, Yeong Wook Song, Anne M. Stevens, Betty P. Tsao, Luis M. Vila, Timothy J. Vyse, Chack Yung Yu, Joel M. Guthridge, Gail R. Bruner, Carl D. Langefeld, Courtney Montgomery, John B. Harley, R. Hal Scofield, Patrick M. Gaffney, Kathy L. Moser

Research output: Contribution to journalResearch Articlepeer-review

73 Scopus citations


Systemic lupus erythematosus (SLE) is considered to be the prototypic autoimmune disease, with a complex genetic architecture influenced by environmental factors. We sought to replicate a putative association at 11p13 not yet exceeding genome-wide significance (p < 5 × 10-8) identified in a genome-wide association study (GWAS). Our GWA scan identified two intergenic SNPs located between PDHX and CD44 showing suggestive evidence of association with SLE in cases of European descent (rs2732552, p = 0.004, odds ratio [OR] = 0.78; rs387619, p = 0.003, OR = 0.78). The replication cohort consisted of >15,000 subjects, including 3562 SLE cases and 3491 controls of European ancestry, 1527 cases and 1811 controls of African American (AA) descent, and 1265 cases and 1260 controls of Asian origin. We observed robust association at both rs2732552 (p = 9.03 × 10-8, OR = 0.83) and rs387619 (p = 7.7 × 10-7, OR = 0.83) in the European samples with pmeta = 1.82 × 10-9 for rs2732552. The AA and Asian SLE cases also demonstrated association at rs2732552 (p = 5 × 10-3, OR = 0.81 and p = 4.3 × 10-4, OR = 0.80, respectively). A meta-analysis of rs2732552 for all racial and ethnic groups studied produced pmeta = 2.36 × 10-13. This locus contains multiple regulatory sites that could potentially affect expression and functions of CD44, a cell-surface glycoprotein influencing immunologic, inflammatory, and oncologic phenotypes, or PDHX, a subunit of the pyruvate dehydrogenase complex.

Original languageEnglish (US)
Pages (from-to)83-91
Number of pages9
JournalAmerican Journal of Human Genetics
Issue number1
StatePublished - Jan 7 2011

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)


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