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Identification of eight genetic variants as novel determinants of dyslipidemia in Japanese by exome-wide association studies.


ABSTRACT: We have performed exome-wide association studies to identify single nucleotide polymorphisms that influence serum concentrations of triglycerides, high density lipoprotein (HDL)-cholesterol, or low density lipoprotein (LDL)-cholesterol or confer susceptibility to hypertriglyceridemia, hypo-HDL-cholesterolemia, or hyper-LDL-cholesterolemia in Japanese. Exome-wide association studies for serum triglycerides (13,414 subjects), HDL-cholesterol (14,119 subjects), LDL-cholesterol (13,577 subjects), hypertriglyceridemia (4742 cases, 8672 controls), hypo-HDL-cholesterolemia (2646 cases, 11,473 controls), and hyper-LDL-cholesterolemia (4489 cases, 9088 controls) were performed with HumanExome-12 DNA Analysis BeadChip or Infinium Exome-24 BeadChip arrays. Twenty-four, 69, or 32 loci were significantly (P < 1.21 × 10-6) associated with serum triglycerides, HDL-cholesterol, or LDL-cholesterol, respectively, with 13, 16, or 9 of these loci having previously been associated with triglyceride-, HDL-cholesterol-, or LDL-cholesterol-related traits, respectively. Two single nucleotide polymorphisms (rs10790162, rs7350481) were significantly related to both serum triglycerides and hypertriglyceridemia; three polymorphisms (rs146515657, rs147317864, rs12229654) were significantly related to both serum HDL-cholesterol and hypo-HDL-cholesterolemia; and six polymorphisms (rs2853969, rs7771335, rs2071653, rs2269704, rs2269703, rs2269702) were significantly related to both serum LDL-cholesterol and hyper-LDL-cholesterolemia. Among polymorphisms identified in the present study, two polymorphisms (rs146515657, rs147317864) may be novel determinants of hypo-HDL-cholesterolemia, and six polymorphisms (rs2853969, rs7771335, rs2071653, rs2269704, rs2269703, rs2269702) may be new determinants of hyper-LDL-cholesterolemia. In addition, 12, 61, 23, or 3 polymorphisms may be new determinants of the serum triglyceride, HDL-cholesterol, or LDL-cholesterol concentrations or of hyper-LDL-cholesterolemia, respectively.

PROVIDER: S-EPMC5503585 | BioStudies |

REPOSITORIES: biostudies

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