To evaluate the association of genetic risk scores (GRS) of LDLR, APOB and proprotein convertase subtilisin-kexin type 9 (PCSK9) SNP and plasma LDL concentrations and to identify lifestyle interactions with the GRS in Korean middle-aged adults.

Korean genome and epidemiology study (KoGES) was conducted to determine genetic variants and lifestyle factors, including nutrient intakes, in a retrospective hospital-based city cohort conducted by the Korean Center for Disease and Control during 2004–2013.

Hospitals in Korea.

Adults aged 40–77 years (n 28 445) without serious diseases.

Subjects with the major alleles (risk allele) of LDLR rs1433099 and rs11557092, APOB rs13306194 and PCSK9 rs11583723 had higher plasma LDL concentration by 1·20-folds than those with the minor alleles. Subjects with High-GRS (major alleles) of the four SNP had higher adjusted OR for plasma total and LDL-cholesterol and TAG concentrations by 1·24-, 1·203- and 1·167-folds, respectively, but not HDL-cholesterol, than those with Low-GRS. Western-style flour-rich dietary patterns, but not balanced Korean-style and rice-based dietary patterns, had interactions with GRS to increase plasma LDL concentrations. Daily energy intake also interacted with GRS. In the high intake of Western-style flour-rich dietary patterns, carriers with High-GRS had much higher plasma LDL concentrations than the Low-GRS. With high energy intake, carriers with High-GRS had much higher plasma LDL concentrations than those with Low-GRS.

Adults with major alleles of four SNP are recommended to have low-energy intakes with a balanced Korean diet need to avoid high-energy intakes especially with Western-style flour-rich diet patterns.