title: Identification of novel genetic susceptibility loci in African American lupus patients in a candidate gene association study.
abstract: OBJECTIVE
  Candidate gene and genome-wide association studies have identified several disease susceptibility loci in lupus patients. These studies have largely been performed in lupus patients who are Asian or of European ancestry. This study was undertaken to examine whether some of these same susceptibility loci increase lupus risk in African American individuals.
  
  
  METHODS
  Single-nucleotide polymorphisms tagging 15 independent lupus susceptibility loci were genotyped in a set of 1,724 lupus patients and 2,024 healthy controls of African American descent. The loci examined included PTPN22, FCGR2A, TNFSF4, STAT4, CTLA4, PDCD1, PXK, BANK1, MSH5 (HLA region), CFB (HLA region), C8orf13-BLK region, MBL2, KIAA1542, ITGAM, and MECP2/IRAK1.
  
  
  RESULTS
  We found the first evidence of genetic association between lupus in African American patients and 5 susceptibility loci (C8orf13-BLK, BANK1, TNFSF4, KIAA1542, and CTLA4; P = 8.0 × 10⁻⁶, P = 1.9 × 10⁻⁵, P = 5.7 × 10⁻⁵, P = 0.00099, and P = 0.0045, respectively). Further, we confirmed the genetic association between lupus and 5 additional lupus susceptibility loci (ITGAM, MSH5, CFB, STAT4, and FCGR2A; P = 7.5 × 10⁻¹¹, P = 5.2 × 10⁻⁸, P = 8.7 × 10⁻⁷ , P = 0.0058, and P = 0.0070, respectively), and provided evidence, for the first time, of genome-wide significance for the association between lupus in African American patients and ITGAM and MSH5 (HLA region).
  
  
  CONCLUSIONS
  These findings provide evidence of novel genetic susceptibility loci for lupus in African Americans and demonstrate that the majority of lupus susceptibility loci examined confer lupus risk across multiple ethnicities.
authors.affiliation: Oklahoma Medical Research Foundation, Oklahoma City, USA.
authors.forename: Elena
authors.initials: E
authors.lastname: Sánchez
authors.forename: Mary E
authors.initials: ME
authors.lastname: Comeau
authors.forename: Barry I
authors.initials: BI
authors.lastname: Freedman
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Kelly
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Kaufman
authors.forename: Carl D
authors.initials: CD
authors.lastname: Langefeld
authors.forename: Elizabeth E
authors.initials: EE
authors.lastname: Brown
authors.forename: Graciela S
authors.initials: GS
authors.lastname: Alarcón
authors.forename: Robert P
authors.initials: RP
authors.lastname: Kimberly
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Edberg
authors.forename: Rosalind
authors.initials: R
authors.lastname: Ramsey-Goldman
authors.forename: Michelle
authors.initials: M
authors.lastname: Petri
authors.forename: John D
authors.initials: JD
authors.lastname: Reveille
authors.forename: Luis M
authors.initials: LM
authors.lastname: Vilá
authors.forename: Joan T
authors.initials: JT
authors.lastname: Merrill
authors.forename: Betty P
authors.initials: BP
authors.lastname: Tsao
authors.forename: Diane L
authors.initials: DL
authors.lastname: Kamen
authors.forename: Gary S
authors.initials: GS
authors.lastname: Gilkeson
authors.forename: Judith A
authors.initials: JA
authors.lastname: James
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Vyse
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Gaffney
authors.forename: Chaim O
authors.initials: CO
authors.lastname: Jacob
authors.forename: Timothy B
authors.initials: TB
authors.lastname: Niewold
authors.forename: Bruce C
authors.initials: BC
authors.lastname: Richardson
authors.forename: John B
authors.initials: JB
authors.lastname: Harley
authors.forename: Marta E
authors.initials: ME
authors.lastname: Alarcón-Riquelme
authors.forename: Amr H
authors.initials: AH
authors.lastname: Sawalha
mesh_terms: D001741:Black or African American / Q000235:genetics*; D000483:Alleles; D056726:Genetic Association Studies; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide