RT Journal Article
T1 Trans-Ethnic Mapping of BANK1 Identifies Two Independent SLE-Risk Linkage Groups Enriched for Co-Transcriptional Splicing Marks.
A1 Martínez-Bueno, Manuel
A1 Oparina, Nina
A1 Dozmorov, Mikhail G
A1 Marion, Miranda C
A1 Comeau, Mary E
A1 Gilkeson, Gary
A1 Kamen, Diane
A1 Weisman, Michael
A1 Salmon, Jane
A1 McCune, Joseph W
A1 Harley, John B
A1 Kimberly, Robert
A1 James, Judith A
A1 Merrill, Joan
A1 Montgomery, Courtney
A1 Langefeld, Carl D
A1 Alarcón-Riquelme, Marta E
K1 BANK1
K1 autoimmune disorders
K1 genetics
K1 systemic lupus erythematosus
K1 transethnic genetic studies
AB BANK1 is a susceptibility gene for several systemic autoimmune diseases in several populations. Using the genome-wide association study (GWAS) data from Europeans (EUR) and African Americans (AA), we performed an extensive fine mapping of ankyrin repeats 1 (BANK1). To increase the SNP density, we used imputation followed by univariate and conditional analysis, combined with a haplotypic and expression quantitative trait locus (eQTL) analysis. The data from Europeans showed that the associated region was restricted to a minimal and dependent set of SNPs covering introns two and three, and exon two. In AA, the signal found in the Europeans was split into two independent effects. All of the major risk associated SNPs were eQTLs, and the risks were associated with an increased BANK1 gene expression. Functional annotation analysis revealed the enrichment of repressive B cell epigenomic marks (EZH2 and H3K27me3) and a strong enrichment of splice junctions. Furthermore, one eQTL located in intron two, rs13106926, was found within the binding site for RUNX3, a transcriptional activator. These results connect the local genome topography, chromatin structure, and the regulatory landscape of BANK1 with co-transcriptional splicing of exon two. Our data defines a minimal set of risk associated eQTLs predicted to be involved in the expression of BANK1 modulated through epigenetic regulation and splicing. These findings allow us to suggest that the increased expression of BANK1 will have an impact on B-cell mediated disease pathways.
YR 2018
FD 2018-08-08
LK http://hdl.handle.net/10668/12821
UL http://hdl.handle.net/10668/12821
LA en
DS RISalud
RD Apr 10, 2025