PART 2 - BEYOND THE GWAS – FUNCTIONAL SIGNIFICANCE
FOR EoE?
This is the exciting conclusion to parsing the findings in Kottyan,
et al., 2014 (1). Just in case you missed it or need a
refresher, here is a link to PART
1 – BACKGROUND TO UNDERSTAND EoE AND THE RESEARCH FINDINGS.
Brief summary of Part
1
After the researchers compared over 1.5 million regions of
the genome between EoE and control subjects, they identified 4 different
regions that were strongly associated with EoE.
Going back to the analogy used in Part 1 – the researchers identified
the flutes among the cacophony of the warming up orchestra. Now, they needed to analyze the melodies
those flutes were playing – stated biologically, they needed to figure out if
any of those flutes (i.e. – regions of DNA identified in the GWAS) played
faulty melodies (i.e. – errors in genes getting expressed that may lead to
EoE). Just because there is a difference in DNA between EoE patients and those
without EoE (controls) doesn’t necessarily mean that it is important
biologically – a flute could play the wrong note, but it may harmonize with the
intended note (e.g. make no difference to EoE). They were looking for a clear,
dissonant “wrong note.” Lead author and researcher on the paper, Dr. Leah
Kottyan relayed to me that in this line of work, identifying the differences in
DNA is the “easy” part. Now came the “hard” part.
