title: A three-stage genome-wide association study combining multilocus test and gene expression analysis for young-onset hypertension in Taiwan Han Chinese.
abstract: BACKGROUND
  Although many large-scale genome-wide association studies (GWASs) have been performed, only a few studies have successfully identified replicable, large-impact hypertension loci; even fewer studies have been done on Chinese subjects. Young-onset hypertension (YOH) is considered to be a more promising target disorder to investigate than late-onset hypertension because of its stronger genetic component.
  
  
  METHODS
  To map YOH genetic variants, we performed a 3-stage study combining 1st-stage multilocus GWASs, 2nd-stage gene expression analysis, and 3rd-stage multilocus confirmatory study.
  
  
  RESULTS
  In the 1st stage, Illumina550K data from 400 case-control pairs were used, and 22 genes flanked by 14 single nucleotide polymorphism (SNP) septets (P values adjusted for false discovery rate (pFDR) < 3.16×10(-7)) were identified. In the 2nd stage, differential gene expression analysis was carried out for these genes, and 5 genes were selected (pFDR < 0.05). In the 3rd stage, we re-examined the finding with an independent set of 592 case-control pairs and with the joint samples (n = 992 case-control pairs). A total of 6 SNP septets flanking C1orf135, GSN, LARS, and ACTN4 remained significant in all 3 stages. Among them, the same septet flanking ACTN4 was also associated with blood pressure traits in the Hong Kong Hypertension Study (HKHS) and in the Wellcome Trust Case-Control Consortium Hypertension Study (WTCCCHS). LARS was detected in the HKHS, but not in the WTCCCHS. GSN may be specific to Taiwanese individuals because it was not found by either the HKHS or the WTCCCHS.
  
  
  CONCLUSIONS
  Our study identified 4 previously unknown YOH loci in Han Chinese. Identification of these genes enriches the hypertension susceptibility gene list, thereby shedding light on the etiology of hypertension in Han Chinese.
authors.affiliation: Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Kuang-Mao
authors.initials: KM
authors.lastname: Chiang
authors.forename: Hsin-Chou
authors.initials: HC
authors.lastname: Yang
authors.forename: Yu-Jen
authors.initials: YJ
authors.lastname: Liang
authors.forename: Jaw-Wen
authors.initials: JW
authors.lastname: Chen
authors.forename: Shiaw-Min
authors.initials: SM
authors.lastname: Hwang
authors.forename: Hung-Yun
authors.initials: HY
authors.lastname: Ho
authors.forename: Chih-Tai
authors.initials: CT
authors.lastname: Ting
authors.forename: Tsung-Hsien
authors.initials: TH
authors.lastname: Lin
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: Hsin-Bang
authors.initials: HB
authors.lastname: Leu
authors.forename: Wei-Hsian
authors.initials: WH
authors.lastname: Yin
authors.forename: Ting-Yu
authors.initials: TY
authors.lastname: Chiu
authors.forename: Chin-Iuan
authors.initials: CI
authors.lastname: Chen
authors.forename: Shing-Jong
authors.initials: SJ
authors.lastname: Lin
authors.forename: G Neil
authors.initials: GN
authors.lastname: Thomas
authors.forename: Brian
authors.initials: B
authors.lastname: Tomlinson
authors.forename: Youling
authors.initials: Y
authors.lastname: Guo
authors.forename: Hong-Sheng
authors.initials: HS
authors.lastname: Gui
authors.forename: Pak Chung
authors.initials: PC
authors.lastname: Sham
authors.forename: Tai-Hing
authors.initials: TH
authors.lastname: Lam
authors.forename: Wen-Harn
authors.initials: WH
authors.lastname: Pan
mesh_terms: D000185:Actinin / Q000235:genetics; D000328:Adult; D017668:Age of Onset; D044466:Asian People / Q000235:genetics*; D001794:Blood Pressure / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics; D016022:Case-Control Studies; D002681:China / Q000208:ethnology; D004268:DNA-Binding Proteins; D005260:Female; D018260:Gelsolin / Q000235:genetics; D005786:Gene Expression Regulation; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D006973:Hypertension / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2 / Q000235:genetics; D018570:Risk Assessment; D012307:Risk Factors; D013624:Taiwan / Q000453:epidemiology
chemical_list: C111453:ACTN4 protein, human; C553277:AUNIP protein, human; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D018260:Gelsolin; D000185:Actinin; C516772:PTPRF protein, human; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2
keywords: Han Chinese; blood pressure; gene expression; genome-wide association study; hypertension; multilocus test; single nucleotide polymorphisms; young-onset hypertension.