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SUMMARY:Gene regulatory mechanisms of non-coding autoimmune risk loci in p
 rimary B cells
DTSTART;TZID=Europe/London:20260605T091500
DTEND;TZID=Europe/London:20260605T101500
DTSTAMP:20260527T025427Z
UID:bba55de3-064a-f111-bec6-0022483ffca9
CREATED:20260507T112137Z
DESCRIPTION:Genome-wide association studies have discovered thousands of g
 enetic variants linked to autoimmune disease\, and yet the underlying mole
 cular pathways have remained elusive. We curated risk loci across >30 auto
 immune traits to reveal overlapping genetic signatures\, before performing
  a high-throughput single-cell multi-omic CRISPR activation screen in prim
 ary human B cells to experimentally map 362 target genes regulated by risk
  loci. Direct measurement of cis-regulatory element transcription revealed
  how coordinated activation of distal risk loci may mediate pleiotropy bet
 ween autoimmune traits. Finally\, we identify a gain-of-function lupus-ass
 ociated variant that regulates the transcription factor REL that subsequen
 tly binds dozens of risk loci and target genes. Our study provides a valua
 ble resource linking risk loci with cis-regulatory targets and advances ou
 r understanding of the shared genetic mechanisms in autoimmunity.
LAST-MODIFIED:20260507T112647Z
SPEAKER:Dr Hamish King
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