title: A genome-wide association study reveals a quantitative trait locus of adiponectin on CDH13 that predicts cardiometabolic outcomes.
abstract: OBJECTIVE
  The plasma adiponectin level, a potential upstream and internal facet of metabolic and cardiovascular diseases, has a reasonably high heritability. Whether other novel genes influence the variation in adiponectin level and the roles of these genetic variants on subsequent clinical outcomes has not been thoroughly investigated. Therefore, we aimed not only to identify genetic variants modulating plasma adiponectin levels but also to investigate whether these variants are associated with adiponectin-related metabolic traits and cardiovascular diseases.
  
  
  METHODS
  We conducted a genome-wide association study (GWAS) to identify quantitative trait loci (QTL) associated with high molecular weight forms of adiponectin levels by genotyping 382 young-onset hypertensive (YOH) subjects with Illumina HumanHap550 SNP chips. The culpable single nucleotide polymorphism (SNP) variants responsible for lowered adiponectin were then confirmed in another 559 YOH subjects, and the association of these SNP variants with the risk of metabolic syndrome (MS), type 2 diabetes mellitus (T2DM), and ischemic stroke was examined in an independent community-based prospective cohort, the CardioVascular Disease risk FACtors Two-township Study (CVDFACTS, n = 3,350).
  
  
  RESULTS
  The SNP (rs4783244) most significantly associated with adiponectin levels was located in intron 1 of the T-cadherin (CDH13) gene in the first stage (P = 7.57 × 10(-9)). We replicated and confirmed the association between rs4783244 and plasma adiponectin levels in an additional 559 YOH subjects (P = 5.70 × 10(-17)). This SNP was further associated with the risk of MS (odds ratio [OR] = 1.42, P = 0.027), T2DM in men (OR = 3.25, P = 0.026), and ischemic stroke (OR = 2.13, P = 0.002) in the CVDFACTS.
  
  
  CONCLUSIONS
  These findings indicated the role of T-cadherin in modulating adiponectin levels and the involvement of CDH13 or adiponectin in the development of cardiometabolic diseases.
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Chia-Min
authors.initials: CM
authors.lastname: Chung
authors.forename: Tsung-Hsien
authors.initials: TH
authors.lastname: Lin
authors.forename: Jaw-Wen
authors.initials: JW
authors.lastname: Chen
authors.forename: Hsin-Bang
authors.initials: HB
authors.lastname: Leu
authors.forename: Hsin-Chou
authors.initials: HC
authors.lastname: Yang
authors.forename: Hung-Yun
authors.initials: HY
authors.lastname: Ho
authors.forename: Chih-Tai
authors.initials: CT
authors.lastname: Ting
authors.forename: Sheng-Hsiung
authors.initials: SH
authors.lastname: Sheu
authors.forename: Wei-Chuan
authors.initials: WC
authors.lastname: Tsai
authors.forename: Jyh-Hong
authors.initials: JH
authors.lastname: Chen
authors.forename: Shing-Jong
authors.initials: SJ
authors.lastname: Lin
authors.forename: Yuan-Tsong
authors.initials: YT
authors.lastname: Chen
authors.forename: Wen-Harn
authors.initials: WH
authors.lastname: Pan
mesh_terms: D052242:Adiponectin / Q000097:blood / Q000235:genetics*; D000328:Adult; D001786:Blood Glucose / Q000235:genetics / Q000378:metabolism; D002545:Brain Ischemia / Q000097:blood / Q000235:genetics; D015820:Cadherins / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000235:genetics*; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D020521:Stroke / Q000097:blood / Q000235:genetics
chemical_list: D052242:Adiponectin; D001786:Blood Glucose; D015820:Cadherins; C099972:H-cadherin