title: Association of the BANK 1 R61H variant with systemic lupus erythematosus in Americans of European and African ancestry.
abstract: Recently an association was demonstrated between the single nucleotide polymorphism (SNP), rs10516487, within the B-cell gene BANK1 and systemic lupus erythematosus (SLE) as a consequence of a genome wide association study of this disease in European and Argentinean populations. In a bid for replication, we examined the effects of the R61H non-synonymous variant with respect to SLE in our genotyped American cohorts of European and African ancestry. Utilizing data from our ongoing genome-wide association study in our cohort of 178 Caucasian SLE cases and 1808 Caucasian population-based controls plus 148 African American (AA) SLE cases and 1894 AA population-based controls we investigated the association of the previously described non-synonymous SNP at the BANK1 locus with the disease in the two ethnicities separately. Using a Fisher's exact test, the minor allele frequency (MAF) of rs10516487 in the Caucasian cases was 22.6% while it was 31.2% in Caucasian controls, yielding a protective odds ratio (OR) of 0.64 (95% CI 0.49-0.85; one-sided p = 7.07 × 10(-4)). Furthermore, the MAF of rs10516487 in the AA cases was 18.7% while it was 23.3% in AA controls, yielding a protective OR of 0.75 (95% CI 0.55-1.034; one-sided p = 0.039). The OR of the BANK1 variant in our study cohorts is highly comparable with that reported previously in a South American/European SLE case-control cohort (OR = 0.72). As such, R61H in the BANK1 gene confers a similar magnitude of SLE protection, not only in European Americans, but also in African Americans.
authors.affiliation: Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, PA, USA ; Department of Pediatrics and Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA ; Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
authors.forename: Struan Fa
authors.initials: SF
authors.lastname: Grant
authors.forename: Michelle
authors.initials: M
authors.lastname: Petri
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Bradfield
authors.forename: Cecilia E
authors.initials: CE
authors.lastname: Kim
authors.forename: Erin
authors.initials: E
authors.lastname: Santa
authors.forename: Kiran
authors.initials: K
authors.lastname: Annaiah
authors.forename: Edward C
authors.initials: EC
authors.lastname: Frackelton
authors.forename: Joseph T
authors.initials: JT
authors.lastname: Glessner
authors.forename: F George
authors.initials: FG
authors.lastname: Otieno
authors.forename: Julie L
authors.initials: JL
authors.lastname: Shaner
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Smith
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Eckert
authors.forename: Rosetta M
authors.initials: RM
authors.lastname: Chiavacci
authors.forename: Marcin
authors.initials: M
authors.lastname: Imielinski
authors.forename: Kathleen E
authors.initials: KE
authors.lastname: Sullivan
authors.forename: Hakon
authors.initials: H
authors.lastname: Hakonarson
keywords: African Americans; BANK1 gene; European Americans; systemic lupus erythematosus