The third day at AGBT finally saw decent weather, with temperatures pushing into the mid-sixties.  That’s almost as high as the atypically warm weather St. Louis is having right now.  It’s just not fair.  Fortunately, the sessions were exciting enough to keep most of us indoors anyway.

Howard McLeod on Pharmacogenomics

There was a provocative and entertaining talk by Howard McLeod (of UNC, formerly of WashU) on using the genome to optimize drug therapy.  He opened with the challenges faced by clinicians who treat their patients with drugs – there are multiple active regimens for most diseases, and the right one is prescribed only 50% of the time.  Complications like variation in response and unpredictable toxicity add to the difficulty of optimizing patient treatments.  While the speaker emphasized that DNA is not the only answer, he admitted that it does seem to be getting the most traction.  He went on to describe my favorite poster-child of pharmacogenetics – warfarin, an oral anticoagulant prescribed to more than 2 million patients for year – in which the variation in maintenance dose can be as high as 50-fold from patient to patient.  One of the pioneers of warfarin pharmacogenetics is Brian Gage, a colleague of mine at Washington University.  In 2007, warfarin was the first drug for which the FDA added genetic information to the label: genotypes in VKORC1 (the target) and CYP2C9 (the metabolizer), which, together with age, body size, and drug interactions, explain nearly 60% of the variability of warfarin dose.  There’s a free tool (http://www.WarfarinDosing.org) that lets clinicians incorporate all of these data into a dose decision engine.

Capture Technologies Abound

Richard Gibbs and Matt Bainbridge gave talks concerning Baylor’s well known Nimblegen-based capture system.  Most of the groups running capture now do so on the HapMap/1000 Genomes pilot samples, which are especially powerful because of the broad genotyping information available from the HapMap data sets.  A highlight of the sessions for me was the presentation of WashU’s solution-based capture platform, WU-CAP, which performed comparably to Nimblegen solid-phase capture but also can be sequenced quite easily on Illumina.  What’s incredible about all capture platforms presented is that they’re reporting dbSNP concordances in the 80-95% range, which is higher than I typically see in whole-genome and PCR-targeted sequencing.  Since variant prediction is my main area of interest, you can guess how excited I am about these platforms.

Daniel MacArthur Also Delivers

I can at last offer unbiased scientific endorsement of my blogging colleague Daniel MacArthur (Genetic Future), who presented some of his work on variation around the ACTN3 gene.  The story of one particular variant (R577X) was particularly fascinating.  Evidently the 20% of human populations that are homozygous-variant (XX) exhibit a marked reduction in muscle strength and explosive power.  As such they’re highly under-represented in Olympic sprinters, for example.  Yet there’s a trade-off in that XX individuals have better muscle endurance and faster recovery, and as you could guess, the allele is very common among long distance runners.  Well done, Daniel, fascinating stuff.