APOE and metabolic disease: In addition to mental and endocrine/metabolic disorders, the APOE e4 risk allele was also associated with an increased risk of circulatory system disorders, such as coronary atherosclerosis (P = 2.0 × 10− 22), ischemic heart disease (P = 3.6 × 10− 17), cerebral ischemia (P = 3.2 × 10− 5), and cerebrovascular disease (P = 2.9 × 10− 5).