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UID:20250720T055829EDT-1580OHk0MB@132.216.98.100
DTSTAMP:20250720T095829Z
DESCRIPTION:A sex-specific evolutionary interaction between ADCY9 and CETP
 \n\nJulie Hussin\, University of Montreal\n	Tuesday November 16\, 12-1pm\n	Z
 oom Link: https://mcgill.zoom.us/j/85428056343\n\nAbstract: Genetic variab
 ility impacts drug response\, which complicates drug discovery and efficac
 y assessment in clinical trials. Previously\, the rs1967309 variant in the
  adenylyl cyclase type 9 (ADCY9) gene was found to be associated with clin
 ical responses to the cholesteryl ester transfer protein (CETP) modulator 
 dalcetrapib\, but the molecular mechanism behind this association remains 
 unknown. Using an approach that combines population genomics\, transcripto
 mics and phenotype screening thanks to multiple databases\, our group has 
 identified a novel sex-specific gene-gene interaction between ADCY9 and CE
 TP detected in the Peruvian population from the 1000 Genomes project\, whi
 ch replicates in the independent LIMAA cohort of over 3\,400 Peruvians. An
 alyses of RNA-seq data from two cohorts (CaG\, GTEx) further revealed sex-
  specific epistatic effects on CETP expression levels in multiple tissues 
 and we see significant interaction effects with sex on cardiovascular phen
 otypes in the UK Biobank\, in line with the sex-specific genotype combinat
 ions found in Peruvians at these loci. The relationship uncovered indicate
 s that the biological link between dalcetrapib’s pharmacogene ADCY9 and th
 e drug target CETP is modulated by sex. Few such interactions have been id
 entified making this a novel finding that\, we hope\, will motivate more r
 esearch and methods to look for such effects.\n
DTSTART:20211116T170000Z
DTEND:20211116T180000Z
LOCATION:CA\, QC
SUMMARY:QLS Seminar Series - Julie Hussin
URL:/qls/channels/event/qls-seminar-series-julie-hussi
 n-334554
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