Blood lipid-related low-frequency variants in LDLR and PCSK9 are associated with onset age and risk of myocardial infarction in Japanese.

ABSTRACT: Recent studies have revealed the importance of rare variants in myocardial infarction (MI) susceptibility in European populations. Because genetic architectures vary in different populations, we investigated how they contribute to MI susceptibility in Japanese subjects. We performed targeted sequencing of 36 coronary artery disease risk genes, identified by genome-wide association studies, in 9,956 cases and 8,373 controls. Gene-based association tests identified significant enrichment of rare variants in LDLR and PCSK9 in MI cases. We identified 52 (novel 22) LDLR variants predicted to be damaging. Carriers of these variants showed a higher risk of MI (carriers/non-carriers 89/9867 in cases, 17/8356 controls, OR = 4.4, P = 7.2 × 10-10), higher LDL-cholesterol levels and younger age of ons

SUBMITTER: Tajima T 

PROVIDER: S-EPMC5970143 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature