Dataset Information

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.

SUBMITTER: Grant SF

PROVIDER: S-EPMC3681036 | biostudies-literature | 2009

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Association of the BANK 1 R61H variant with systemic lupus erythematosus in Americans of European and African ancestry.

Grant Struan Fa SF Petri Michelle M Bradfield Jonathan P JP Kim Cecilia E CE Santa Erin E Annaiah Kiran K Frackelton Edward C EC Glessner Joseph T JT Otieno F George FG Shaner Julie L JL Smith Ryan M RM Eckert Andrew W AW Chiavacci Rosetta M RM Imielinski Marcin M Sullivan Kathleen E KE Hakonarson Hakon H

The application of clinical genetics 20091209

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 ass ...[more]

PMID: 23776345

Similar Datasets

Project description:BACKGROUND:African Americans with systemic lupus erythematosus (SLE) have increased renal disease compared to Caucasians, but differences in other comorbidities have not been well-described. We used an electronic health record (EHR) technique to test for differences in comorbidities in African Americans compared to Caucasians with SLE. METHODS:We used a de-identified EHR with 2.8 million subjects to identify SLE cases using a validated algorithm. We performed phenome-wide association studies (PheWAS) comparing African American to Caucasian SLE cases and African American SLE cases to matched non-SLE controls. Controls were age, sex, and race matched to SLE cases. For multiple testing, a false discovery rate (FDR) p value of 0.05 was used. RESULTS:We identified 270 African Americans and 715 Caucasians with SLE and 1425 matched African American controls. Compared to Caucasians with SLE adjusting for age and sex, African Americans with SLE had more comorbidities in every organ system. The most striking included hypertension odds ratio (OR) = 4.25, FDR p = 5.49 × 10- 15; renal dialysis OR = 10.90, FDR p = 8.75 × 10- 14; and pneumonia OR = 3.57, FDR p = 2.32 × 10- 8. Compared to the African American matched controls without SLE, African Americans with SLE were more likely to have comorbidities in every organ system. The most significant codes were renal and cardiac, and included renal failure (OR = 9.55, FDR p = 2.26 × 10- 40) and hypertensive heart and renal disease (OR = 8.08, FDR p = 1.78 × 10- 22). Adjusting for race, age, and sex in a model including both African American and Caucasian SLE cases and controls, SLE was independently associated with renal, cardiovascular, and infectious diseases (all p <?0.01). CONCLUSIONS:African Americans with SLE have an increased comorbidity burden compared to Caucasians with SLE and matched controls. This increase in comorbidities in African Americans with SLE highlights the need to monitor for cardiovascular and infectious complications.

Project description:ObjectiveSystemic lupus erythematosus (SLE) is a chronic autoimmune disease with a strong genetic component. We undertook the present work to perform the first genome-wide association study on individuals from the Americas who are enriched for Native American heritage.MethodsWe analyzed 3,710 individuals from the US and 4 countries of Latin America who were diagnosed as having SLE, and healthy controls. Samples were genotyped with HumanOmni1 BeadChip. Data on out-of-study controls genotyped with HumanOmni2.5 were also included. Statistical analyses were performed using SNPtest and SNPGWA. Data were adjusted for genomic control and false discovery rate. Imputation was performed using Impute2 and, for classic HLA alleles, HiBag. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated.ResultsThe IRF5-TNPO3 region showed the strongest association and largest OR for SLE (rs10488631: genomic control-adjusted P [Pgcadj ] = 2.61 × 10(-29), OR 2.12 [95% CI 1.88-2.39]), followed by HLA class II on the DQA2-DQB1 loci (rs9275572: Pgcadj = 1.11 × 10(-16), OR 1.62 [95% CI 1.46-1.80] and rs9271366: Pgcadj = 6.46 × 10(-12), OR 2.06 [95% CI 1.71-2.50]). Other known SLE loci found to be associated in this population were ITGAM, STAT4, TNIP1, NCF2, and IRAK1. We identified a novel locus on 10q24.33 (rs4917385: Pgcadj = 1.39 × 10(-8)) with an expression quantitative trait locus (eQTL) effect (Peqtl = 8.0 × 10(-37) at USMG5/miR1307), and several new suggestive loci. SLE risk loci previously identified in Europeans and Asians were corroborated. Local ancestry estimation showed that the HLA allele risk contribution is of European ancestral origin. Imputation of HLA alleles suggested that autochthonous Native American haplotypes provide protection against development of SLE.ConclusionOur results demonstrate that studying admixed populations provides new insights in the delineation of the genetic architecture that underlies autoimmune and complex diseases.

Dataset Information

Association of the BANK 1 R61H variant with systemic lupus erythematosus in Americans of European and African ancestry.

Publications

Association of the BANK 1 R61H variant with systemic lupus erythematosus in Americans of European and African ancestry.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets