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.