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Developing Multi-Gene Biomarker Tests for Drug Therapy: Emphasis on Regulatory Variants and Epistasis

Monday, 27 October 2014 at 15:30

Add to Calendar ▼2014-10-27 15:30:002014-10-27 16:30:00Europe/LondonDeveloping Multi-Gene Biomarker Tests for Drug Therapy: Emphasis on Regulatory Variants and EpistasisSELECTBIOenquiries@selectbiosciences.com

The genetic background of a patient strongly influences response to drugs, affecting both efficacy and adverse drug reactions (ADRs).  Therefore, predictive genetic biomarker test have the potential substantially to improve treatment outcomes; however, known genetic variants account for only a portion of the overall heritability estimated from sibling studies – a gap termed the ‘missing heritability’ of complex phenotypes (mostly applied to common disorders).  Research in our Center focuses on discovery of causative variants that impact pharmacokinetic and pharmacodynamic drug effects, with the hypothesis that a majority of causative variants are regulatory or affect RNA biology.  These can be revealed by measuring allelic RNA ratios in human target tissues, either on a gene-by-gene basis or genome-wide with next generation sequencing (RNAseq).  We have identified such frequent variants in up to 20 key drug target genes.  Since each of these variants alone may not have sufficiently strong effect on outcomes, we propose that epistatic interactions between variants and genes (as a result of co-evolution) have the potential to narrow the gap and yield highly predictive genetic biomarker panels.   Examples will be presented.   Supported by NIH U01 GM092655.