BEGIN:VCALENDAR VERSION:2.0 PRODID:-//ox.ac.uk//NONSGML oxford.event//EN X-WR-TIMEZONE:Europe/London BEGIN:VTIMEZONE TZID:Europe/London X-LIC-LOCATION:Europe/London BEGIN:DAYLIGHT DTSTART:19700329T010000 RRULE:FREQ=YEARLY;BYDAY=-1SU;BYMONTH=3 TZNAME:BST TZOFFSETFROM:+0000 TZOFFSETTO:+0100 END:DAYLIGHT BEGIN:STANDARD DTSTART:19701025T020000 RRULE:FREQ=YEARLY;BYDAY=-1SU;BYMONTH=10 TZNAME:GMT TZOFFSETFROM:+0100 TZOFFSETTO:+0000 END:STANDARD END:VTIMEZONE BEGIN:VEVENT SUMMARY:The Biobank Rare Variant consortium powers the discovery of rare g enetic associations through global collaboration DTSTART;TZID=Europe/London:20260526T093000 DTEND;TZID=Europe/London:20260526T103000 DTSTAMP:20260515T220025Z UID:bdf1a3c6-3a28-f111-88b3-7c1e5278f34a CREATED:20260325T110720Z DESCRIPTION:For our next talk\, in the BDI/CHG (gen)omics Seminar series\, we will be hearing from Duncan Palmer\, SMARTbiomed Senior Research Fello w\; co-lead\, the Biobank Rare-Variant Consortium (BRaVa)\, BDI and Depart ment of Statistics\, University of Oxford. We’re delighted to host Dunca n in what promises to be a great talk!\n\nDate: Tuesday 26 May\nTime: 9:30 am – 10:30 am\nTalk title: The Biobank Rare Variant consortium powers t he discovery of rare genetic associations through global collaboration\nLo cation: Big Data Institute\, Seminar Room 0\n\nAbstract\nRare coding varia nts can have large effects on disease risk\, but their discovery is fundam entally constrained by sample size. The low frequency of these variants li mits power even in the largest individual biobanks\, particularly for dise ase endpoints. Here we introduce the Biobank Rare Variant Analysis (BRaVa) consortium\, which unites 10 biobanks and cohorts\, comprising over 1.25 million individuals with matched genetic and healthcare record data\, to a dvance our understanding of the genetic basis of human disease.\n\nWe perf ormed gene-based meta-analyses of rare coding variation across 32 disease endpoints and 12 quantitative traits in diverse populations. Aggregating e vidence across biobanks and ancestries substantially increased power\, ide ntifying 579 gene-trait associations\, including 36 not previously reporte d in prior studies or curated genetic association resources following syst ematic literature curation. Notably\, 42.5% of associations were not detec ted in any individual biobank\, and 111 were identified only through cross -ancestry meta-analysis\, demonstrating that large-scale integration enabl es discovery beyond the reach of single cohorts\; improvements in discover y were also observed at the variant level\, where 15.8% of associations we re detectable only through meta-analysis.\n\nEffect size estimates were co nsistent across genetic ancestries with concordant directions of effect\, supporting the generalizability of rare variant associations. The identifi ed signals implicate biological pathways spanning transcriptional and epig enetic regulation\, metabolic homeostasis\, vascular and epithelial biolog y\, and immune function. These findings highlight the ability of rare codi ng variation to directly implicate causal genes and disease mechanisms. Fo r example\, damaging variation in ANKRD12 implicates dysregulated transcri ptional control of inflammatory pathways in asthma and chronic obstructive pulmonary disease\, while ultra-rare predicted loss-of-function variants in NAA15 link protein acetylation processes to type 2 diabetes risk.\n\nTo gether\, BRaVa establishes a scalable framework for rare variant meta-anal ysis across global biobanks and enables systematic discovery of gene-level mechanisms underlying complex human disease\, accelerating the identifica tion of biologically grounded therapeutic targets as sequencing resources continue to expand. LAST-MODIFIED:20260512T095413Z LOCATION:Big Data Institute - Lower Ground Seminar Room 0\, Lower Ground S eminar Room 0 Big Data Institute Old Road Campus Oxford Oxfordshire OX3 7L F United Kingdom SPEAKER:Duncan Palmer (BDI\, University of Oxford) END:VEVENT END:VCALENDAR