@misc{10481/57878,
year = {2018},
month = {8},
url = {http://hdl.handle.net/10481/57878},
abstract = {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, combinedwith 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 epigenomicmarks
(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.},
organization = {The work presented in this paper has been supported by the Ministerio de Economía y Competitividad,
Spain (SAF2016-78631-P), partly co-financed by FEDER funds of the European Union, the Gustaf den V:e-80-års
Fond and the Swedish Association against Rheumatism to M.E.A-R. In addition, this work was financed by the
NIH P01 grant P01-AI-083194 to C.D.L., J.B.H., R.K., and M.E.A-R. JBH: NIH grants: R01 AI024717, U01 HG00866,
P30 AR070549 and U01 AI130830 and the US Department of Veterans Affairs: I01 BX001834.C.D.L.: Center for
Public Health Genomics. R.K.: NIH grant R01-AR33062. J.A.J.: NIH grants U54GM104938, P30AR053483.},
publisher = {MDPI},
keywords = {Autoimmune disorders},
keywords = {Systemic lupus erythematosus},
keywords = {Genetics},
keywords = {BANK1},
keywords = {Transethnic genetic studies},
title = {Trans-Ethnic Mapping of BANK1 Identifies Two Independent SLE-Risk Linkage Groups Enriched for Co-Transcriptional Splicing Marks},
doi = {10.3390/ijms19082331},
author = {Martínez Bueno, Manuel},
}