In the April 11th issue of JAMA Tom Morgan and Rick Lifton report a large "Replication" Study intended to identify at risk polymorphisms. I remember Tom running all over Yale collecting samples while I was a medical student rotating through genetics there. Personally I am surprised that the press did not jump all over this study. They evaluated 85 previously studied markers and found absolutely none were linked to increased risk of heart attack. However family history of MI was higher in cases than controls, the racial subtype was Caucasian, the study identified each gene polymorphism individually. What this alerts me to is the shortcoming of candidate gene analysis (looking for genes based on mechanism of disease process). More importantly it puts an ALERT out that testing for MI predisposition is not ready for prime time quite yet, at least in a pan screening form. Perhaps nuanced testing in specific groups like ALOX5AP in Icelandic and Scottish patients will be the best way to stratify care. The Gene Sherpa says- Hold on to testing for MI for now. Subgroup analysis will need to be done....again. Soon we will have whole genome analysis of risk genes and that will help solve this mystery. I hope Tom is doing well at Wash U St Louis. If anyone sees him tell him Steve Murphy says hi.