Although the present study is not a direct test of the effects of LDL-C on IS risk (but, instead, is a test of PCSK9 levels on IS risk), the magnitude of association of rs11591147 (R46L) with CHD risk is broadly consistent with that predicted from Mendelian randomization studies of LDL-C and CHD.33 Here, PCSK9 is linked to coronary artery disorder.