IRS1 and acute coronary syndrome: In addition, Harrap et al reported a subthreshold linkage peak containing IRS1 in a genome-wide scan of 61 sibling pairs with acute coronary syndrome, adding to interest in the IRS1 locus as a cardiac candidate gene.[28] However, IRS1 was not associated with the primary occurrence of ACS in our previous case-control analysis.[5] Moreover, due to the rarity of arginine homozygous genotype, the association in our study population was largely based on the deaths of 2 individuals among the 3 with the A/A genotype.