biostudies-literatureUnknownWiley MMIntramural NIH HHSNIDCR NIH HHSNIA NIH HHSNIEHS NIH HHSNIAID NIH HHSNHLBI NIH HHSNHGRI NIH HHSNCI NIH HHSNIAMS NIH HHSFine mapping and bioinformatic analysis of the <i>DDX6-CXCR5</i> genetic risk association in Sjögren's Disease (SjD) and Systemic Lupus Erythematosus (SLE) identified five common SNPs with functional evidence in immune cell types: rs4938573, rs57494551, rs4938572, rs4936443, rs7117261. Functional interrogation of nuclear protein binding affinity, enhancer/promoter regulatory activity, and chromatin-chromatin interactions in immune, salivary gland epithelial, and kidney epithelial cells revealed cell type-specific allelic effects for all five SNPs that expanded regulation beyond effects on <i>DDX6</i> and <i>CXCR5</i> expression. Mapping the local chromatin regulatory network revealed several additional genes of interest, including <i>lnc-PHLDB1-1</i>. Collectively, functional characterizatbioRxiv : the preprint server for biology2023.10.05.561076https://www.ebi.ac.uk/biostudies/studies/S-EPMC11275775biostudies-literatureVariants in the &lt;i&gt;DDX6-CXCR5&lt;/i&gt; autoimmune disease risk locus influence the regulatory network in immune cells and salivary gland.PMC11275775UM1 AI144292Z01 DE000704R61 AR076803U01 HG004446HHSN268201100011IR01 AR071947P50 AR060804HHSN268200782096CR01 ES011740P30 AR073750R03 DE029800HHSN268201200008IN01 DE032636R01 AR074310R21 AR079089HHSN268201100011CRC2 AG036495HHSN268201200008CP50 CA097007R01 AR065953R01 AR071410R33 AR076803R01 AR073855P50 CA093459RC4 AG039029P30 AR070155R01 CA133996U01 DE028891Glenn SBUK Primary Sjögren’s Syndrome RegistryFugmann CWallace DJJonsson RNorheim KBNordmark GKhanam SPalm ONg WFJoachims MLOlsson PShiboski CHDand NTsao BPWiley MMAdrianto IMartin JLessard CJKhatri BJohnsen SJASjowall CJames JACriswell LAWitte TSjögren’s International Collaborative Clinical Alliance (SICCA)Gottenberg JEWarner BMForsblad-d'Elia HBjork ABrun JGJensen JLRonnblom LImgenberg-Kreuz JRhodus NLEngelke FGrundahl KMWahren-Herlenius MBaecklund ERasmussen AMorris DLEriksson PSkarstein KJonsson MVScofield RHTombleson PBucher SMKim KPers JOGuthridge JMFarris ADBrennan MTGaffney PMAlarcon-Riquelme MEStolarczyk AMBowman SJAnaya JMVital EMGong CVyse TJKvarnstrom MNocturne GThorlacius GEVenuturupalli SRadfar LTaylor KEMariette XEloranta MLAqrawi LABae SCSivils KLMandl TAppel SOmdal RHammenfors DKelly JARischmueller MPRECISESADS Clinical ConsortiumTessneer KLfalseVariants in the &lt;i&gt;DDX6-CXCR5&lt;/i&gt; autoimmune disease risk locus influence the regulatory network in immune cells and salivary gland.Fine mapping and bioinformatic analysis of the <i>DDX6-CXCR5</i> genetic risk association in Sjögren's Disease (SjD) and Systemic Lupus Erythematosus (SLE) identified five common SNPs with functional evidence in immune cell types: rs4938573, rs57494551, rs4938572, rs4936443, rs7117261. Functional interrogation of nuclear protein binding affinity, enhancer/promoter regulatory activity, and chromatin-chromatin interactions in immune, salivary gland epithelial, and kidney epithelial cells revealed cell type-specific allelic effects for all five SNPs that expanded regulation beyond effects on <i>DDX6</i> and <i>CXCR5</i> expression. Mapping the local chromatin regulatory network revealed several additional genes of interest, including <i>lnc-PHLDB1-1</i>. Collectively, functional characterizat2023-01-01T00:00:00Z2023 Oct2026-04-19T03:16:25.449Z2024-11-09T11:01:49.842ZS-EPMC112757753907144710.1101/2023.10.05.561076