title: Evaluation of pleiotropic effects among common genetic loci identified for cardio-metabolic traits in a Korean population.
abstract: BACKGROUND
  The genetic contribution to complex diseases or traits, including cardio-metabolic traits, has been elucidated recently by large-scale genome-wide association studies. These genome-wide association studies have indicated that most pleiotropic loci contain genes associated with lipids. Clinically, lipid related abnormalities are strongly associated with other diseases such as type 2 diabetes, coronary artery disease and hypertension. The aim of this study was to evaluate the shared genetic background of lipids and other cardio-metabolic traits.
  
  
  METHODS
  We conducted meta-analyses of the association between 157 published lipid-associated loci and 10 cardio-metabolic traits in 14,028 Korean individuals genotyped using the Exome chip (Illumina HumanExome BeadChip). We also examined whether the pleiotropic effects of such loci constituted independent (i.e., biological) pleiotropy or mediated pleiotropy in these metabolic pathways.
  
  
  RESULTS
  Eighteen lipid-associated loci were significantly associated with one of six cardio-metabolic traits after correction for multiple testing (P < 3.70 × 10(-4)). Region 12q24.12 had pleiotropic effects on fasting plasma glucose, blood pressure and obesity-related traits (body mass index and waist-hip ratio) independent of its effects on the lipid profile. Lipid risk scores, calculated according to whether or not subjects carried the risk allele for lipid traits, were significantly associated with fasting plasma glucose, blood pressure and obesity-related traits.
  
  
  CONCLUSIONS
  The 12q24.12 region showed ethnic-specific genetic pleiotropy among cardio-metabolic traits in this study. Our findings may help to account for molecular mechanisms based on shared genetic background underlying not only dyslipidemia, but also cardiovascular disease and type 2 diabetes.
authors.affiliation: Division of Structural and Functional Genomics, Center for Genome Sciences, National Institute of Health, Centers for Disease Control and Prevention, Cheongju-si, Chungcheongbuk-do, 28159, South Korea. bborumi@gmail.com.
authors.forename: Yun Kyoung
authors.initials: YK
authors.lastname: Kim
authors.affiliation: Division of Structural and Functional Genomics, Center for Genome Sciences, National Institute of Health, Centers for Disease Control and Prevention, Cheongju-si, Chungcheongbuk-do, 28159, South Korea. myhwang85@gmail.com.
authors.forename: Mi Yeong
authors.initials: MY
authors.lastname: Hwang
authors.affiliation: Division of Structural and Functional Genomics, Center for Genome Sciences, National Institute of Health, Centers for Disease Control and Prevention, Cheongju-si, Chungcheongbuk-do, 28159, South Korea. anwltlarkr@gmail.com.
authors.forename: Young Jin
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Division of Structural and Functional Genomics, Center for Genome Sciences, National Institute of Health, Centers for Disease Control and Prevention, Cheongju-si, Chungcheongbuk-do, 28159, South Korea. moon.sanghoon@daum.net.
authors.forename: Sanghoon
authors.initials: S
authors.lastname: Moon
authors.affiliation: Division of Structural and Functional Genomics, Center for Genome Sciences, National Institute of Health, Centers for Disease Control and Prevention, Cheongju-si, Chungcheongbuk-do, 28159, South Korea. smallstar1999@hanmail.net.
authors.forename: Sohee
authors.initials: S
authors.lastname: Han
authors.affiliation: Division of Structural and Functional Genomics, Center for Genome Sciences, National Institute of Health, Centers for Disease Control and Prevention, Cheongju-si, Chungcheongbuk-do, 28159, South Korea. kbj6181@cdc.go.kr.
authors.forename: Bong-Jo
authors.initials: BJ
authors.lastname: Kim
mesh_terms: D044466:Asian People / Q000235:genetics*; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000235:genetics; D001794:Blood Pressure / Q000235:genetics; D015992:Body Mass Index; D002881:Chromosomes, Human, Pair 12; D030562:Databases, Protein; D020869:Gene Expression Profiling / Q000379:methods; D056726:Genetic Association Studies; D056426:Genetic Loci; D058685:Genetic Pleiotropy; D020022:Genetic Predisposition to Disease; D006801:Humans; D008055:Lipids / Q000097:blood / Q000235:genetics; D024821:Metabolic Syndrome / Q000097:blood / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D025941:Protein Interaction Mapping; D056910:Republic of Korea; D049629:Waist-Hip Ratio
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D008055:Lipids
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