Differential genetic associations for systemic lupus erythematosus based on anti-dsDNA autoantibody production

Sharon A. Chung, Kimberly E. Taylor, Robert R. Graham, Joanne Nititham, Annette T. Lee, Ward A. Ortmann, Chaim O. Jacob, Marta E. Alarcón-Riquelme, Betty P. Tsao, John B. Harley, Patrick M. Gaffney, Kathy L. Moser, Michelle Petri, F. Yesim Demirci, M. Ilyas Kamboh, Susan Manzi, Peter K. Gregersen, Carl D. Langefeld, Timothy W. Behrens, Lindsey A. Criswell

Research output: Contribution to journalArticle

Abstract

Systemic lupus erythematosus (SLE) is a clinically heterogeneous, systemic autoimmune disease characterized by autoantibody formation. Previously published genome-wide association studies (GWAS) have investigated SLE as a single phenotype. Therefore, we conducted a GWAS to identify genetic factors associated with anti-dsDNA autoantibody production, a SLE-related autoantibody with diagnostic and clinical importance. Using two independent datasets, over 400,000 single nucleotide polymorphisms (SNPs) were studied in a total of 1,717 SLE cases and 4,813 healthy controls. Anti-dsDNA autoantibody positive (anti-dsDNA +, n = 811) and anti-dsDNA autoantibody negative (anti-dsDNA -, n = 906) SLE cases were compared to healthy controls and to each other to identify SNPs associated specifically with these SLE subtypes. SNPs in the previously identified SLE susceptibility loci STAT4, IRF5, ITGAM, and the major histocompatibility complex were strongly associated with anti-dsDNA + SLE. Far fewer and weaker associations were observed for anti-dsDNA - SLE. For example, rs7574865 in STAT4 had an OR for anti-dsDNA + SLE of 1.77 (95% CI 1.57-1.99, p = 2.0E-20) compared to an OR for anti-dsDNA - SLE of 1.26 (95% CI 1.12-1.41, p = 2.4E-04), with pheterogeneity

Original languageEnglish (US)
Article numbere1001323
JournalPLoS Genetics
Volume7
Issue number3
DOIs
StatePublished - Mar 2011

Fingerprint

lupus erythematosus
antibody formation
Systemic Lupus Erythematosus
Autoantibodies
polymorphism
genome
autoantibodies
major histocompatibility complex
phenotype
single nucleotide polymorphism
Single Nucleotide Polymorphism
Genome-Wide Association Study
autoimmune diseases
Major Histocompatibility Complex
Autoimmune Diseases

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Ecology, Evolution, Behavior and Systematics
  • Cancer Research
  • Genetics(clinical)

Cite this

Chung, S. A., Taylor, K. E., Graham, R. R., Nititham, J., Lee, A. T., Ortmann, W. A., ... Criswell, L. A. (2011). Differential genetic associations for systemic lupus erythematosus based on anti-dsDNA autoantibody production. PLoS Genetics, 7(3), [e1001323]. https://doi.org/10.1371/journal.pgen.1001323

Differential genetic associations for systemic lupus erythematosus based on anti-dsDNA autoantibody production. / Chung, Sharon A.; Taylor, Kimberly E.; Graham, Robert R.; Nititham, Joanne; Lee, Annette T.; Ortmann, Ward A.; Jacob, Chaim O.; Alarcón-Riquelme, Marta E.; Tsao, Betty P.; Harley, John B.; Gaffney, Patrick M.; Moser, Kathy L.; Petri, Michelle; Demirci, F. Yesim; Kamboh, M. Ilyas; Manzi, Susan; Gregersen, Peter K.; Langefeld, Carl D.; Behrens, Timothy W.; Criswell, Lindsey A.

In: PLoS Genetics, Vol. 7, No. 3, e1001323, 03.2011.

Research output: Contribution to journalArticle

Chung, SA, Taylor, KE, Graham, RR, Nititham, J, Lee, AT, Ortmann, WA, Jacob, CO, Alarcón-Riquelme, ME, Tsao, BP, Harley, JB, Gaffney, PM, Moser, KL, Petri, M, Demirci, FY, Kamboh, MI, Manzi, S, Gregersen, PK, Langefeld, CD, Behrens, TW & Criswell, LA 2011, 'Differential genetic associations for systemic lupus erythematosus based on anti-dsDNA autoantibody production', PLoS Genetics, vol. 7, no. 3, e1001323. https://doi.org/10.1371/journal.pgen.1001323
Chung, Sharon A. ; Taylor, Kimberly E. ; Graham, Robert R. ; Nititham, Joanne ; Lee, Annette T. ; Ortmann, Ward A. ; Jacob, Chaim O. ; Alarcón-Riquelme, Marta E. ; Tsao, Betty P. ; Harley, John B. ; Gaffney, Patrick M. ; Moser, Kathy L. ; Petri, Michelle ; Demirci, F. Yesim ; Kamboh, M. Ilyas ; Manzi, Susan ; Gregersen, Peter K. ; Langefeld, Carl D. ; Behrens, Timothy W. ; Criswell, Lindsey A. / Differential genetic associations for systemic lupus erythematosus based on anti-dsDNA autoantibody production. In: PLoS Genetics. 2011 ; Vol. 7, No. 3.
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abstract = "Systemic lupus erythematosus (SLE) is a clinically heterogeneous, systemic autoimmune disease characterized by autoantibody formation. Previously published genome-wide association studies (GWAS) have investigated SLE as a single phenotype. Therefore, we conducted a GWAS to identify genetic factors associated with anti-dsDNA autoantibody production, a SLE-related autoantibody with diagnostic and clinical importance. Using two independent datasets, over 400,000 single nucleotide polymorphisms (SNPs) were studied in a total of 1,717 SLE cases and 4,813 healthy controls. Anti-dsDNA autoantibody positive (anti-dsDNA +, n = 811) and anti-dsDNA autoantibody negative (anti-dsDNA -, n = 906) SLE cases were compared to healthy controls and to each other to identify SNPs associated specifically with these SLE subtypes. SNPs in the previously identified SLE susceptibility loci STAT4, IRF5, ITGAM, and the major histocompatibility complex were strongly associated with anti-dsDNA + SLE. Far fewer and weaker associations were observed for anti-dsDNA - SLE. For example, rs7574865 in STAT4 had an OR for anti-dsDNA + SLE of 1.77 (95{\%} CI 1.57-1.99, p = 2.0E-20) compared to an OR for anti-dsDNA - SLE of 1.26 (95{\%} CI 1.12-1.41, p = 2.4E-04), with pheterogeneity",
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