Genetic loci associated with coronary artery disease harbor evidence of selection and antagonistic pleiotropy

摘要: Traditional genome-wide scans for positive selection have mainly uncovered selective sweeps associated with monogenic traits. While on quantitative traits is much more common, very few signals been detected because of their polygenic nature. We searched underlying coronary artery disease (CAD) in worldwide populations, using novel approaches to quantify relationships between and CAD genetic risk. identified new candidate adaptive loci that appear directly modified by pressures given significant associations These candidates were all uniquely consistently many different male female reproductive suggesting may also targeted these direct effects fitness. This suggests the presence widespread antagonistic-pleiotropic tradeoffs loci, which provides a explanation maintenance high prevalence modern humans. Lastly, we found often gene regulatory variants HapMap3 lymphoblastoid cell lines, further highlights unique biological significance CAD. Our study approach detecting evidence human genomes evolved response CAD-induced other early-life sharing pleiotropic links