Identification of six novel susceptibility loci for dyslipidemia using longitudinal exome-wide association studies in a Japanese population |
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| Authors: | Yoshiki Yasukochi Jun Sakuma Ichiro Takeuchi Kimihiko Kato Mitsutoshi Oguri Tetsuo Fujimaki Hideki Horibe Yoshiji Yamada |
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| Affiliation: | 1. Department of Human Functional Genomics, Advanced Science Research Promotion Center, Mie University, Tsu 514-8507, Japan;2. CREST, Japan Science and Technology Agency, Kawaguchi 332-0012, Japan;3. Computer Science Department, College of Information Science, University of Tsukuba, Tsukuba 305-8573, Japan;4. RIKEN Center for Advanced Intelligence Project, Tokyo 103-0027, Japan;5. Department of Computer Science, Nagoya Institute of Technology, Nagoya 466-8555, Japan;6. Department of Internal Medicine, Meitoh Hospital, Nagoya 465-0025, Japan;7. Department of Cardiology, Kasugai Municipal Hospital, Kasugai 486-8510, Japan;8. Department of Cardiovascular Medicine, Inabe General Hospital, Inabe 511-0428, Japan;9. Department of Cardiovascular Medicine, Gifu Prefectural Tajimi Hospital, Tajimi 507-8522, Japan |
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| Abstract: | Recent genome-wide association studies have identified various dyslipidemia-related genetic variants. However, most studies were conducted in a cross-sectional manner. We thus performed longitudinal exome-wide association studies of dyslipidemia in a Japanese population. We used ~244,000 genetic variants and clinical data of 6022 Japanese individuals who had undergone annual health checkups for several years. After quality control, the association of dyslipidemia-related phenotypes with 24,691 single nucleotide polymorphisms (SNPs) was tested using the generalized estimating equation model. In total, 82 SNPs were significantly (P < 2.03 × 10?6) associated with dyslipidemia phenotypes. Of these SNPs, four (rs74416240 of TCHP, rs925368 of GIT2, rs7969300 of ATXN2, and rs12231744 of NAA25) and two (rs34902660 of SLC17A3 and rs1042127 of CDSN) were identified as novel genetic determinants of hypo-HDL- and hyper-LDL-cholesterolemia, respectively. A replication study using the cross-sectional data of 8310 Japanese individuals showed the association of the six identified SNPs with dyslipidemia-related traits. |
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| Keywords: | Corresponding author at: Department of Human Functional Genomics, Advanced Science Research Promotion Center, Organization for the Promotion of Regional Innovation, Mie University, 1577 Kurima-machiya, Tsu, Mie 514-8507, Japan. Dyslipidemia Exome-wide association study Generalized estimating equation LDL-cholesterol HDL-cholesterol Triglyceride |
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