Genomic convergence of locus-based GWAS meta-analysis identifies DDX11 as a novel Systemic Lupus Erythematosus gene

Mohammad Saeed; Alejandro Ibáñez-Costa; Alejandra María Patiño-Trives; Eduardo Collantes Estevez; María Ángeles Aguirre; Chary López-Pedrera

The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.04.17.047332 doi: bioRxiv preprint DEAD/H (Asp-Glu-Ala-Asp/His) box helicase, DDX11 is a RNA helicase thought to be involved in genome stability. It is located at the 12p11.21 locus that associated with SLE in two GWAS. Moreover, DDX11 was found to be downregulated in SLE in multiple expression datasets and this finding was confirmed with qPCR in SLE monocytes. These findings confirm DDX11, a DNA helicase, as a novel SLE gene. DDX11 mutations cause the Warsaw Breakage Syndrome (WABS), an autosomal recessive cohesinopathy with the clinical triad of severe congenital microcephaly, growth restriction, and sensorineural hearing loss (Eppley et al., 2017) . WABS shows features of genome instability similar to Fanconi anemia (FA). Several genes are involved in the FA pathway which is critical to DNA repair of interstrand crosslinks (ICL). DDX11 functions as a FA pathway backup and its deficiency leads to impaired ICL repair (Abe et al., 2018) . Moreover, DDX11 plays an important role in B-cell immunoglobulin (Ig) diversification (Abe et al., 2018) which makes it an even more interesting candidate gene for SLE. Inhibition of DDX11 expression led to extensive apoptosis in melanoma cells (Bhattacharya et al. 2012 ).