A three-stage genome-wide association study combining multilocus test and gene expression analysis for young-onset hypertension in Taiwan Han Chinese

Research output: Contribution to journalArticlepeer-review

Authors

  • Kuang-Mao Chiang
  • Hsin-Chou Yang
  • Yu-Jen Liang
  • Jaw-Wen Chen
  • Shiaw-Min Hwang
  • Hung-Yun Ho
  • Chih-Tai Ting
  • Tsung-Hsien Lin
  • Sheng-Hsiung Sheu
  • Wei-Chuan Tsai
  • Jyh-Hong Chen
  • Hsin-Bang Leu
  • Wei-Hsian Yin
  • Ting-Yu Chiu
  • Chin-Iuan Chen
  • Shing-Jong Lin
  • Brian Tomlinson
  • Youling Guo
  • Hong-Sheng Gui
  • Pak Chung Sham
  • Tai-Hing Lam
  • Wen-Harn Pan

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.

Details

Original languageEnglish
Pages (from-to)819-27
Number of pages9
JournalAmerican Journal of Hypertension
Volume27
Issue number6
Publication statusPublished - Jun 2014

Keywords

  • Actinin, Adult, Age of Onset, Asian Continental Ancestry Group, Blood Pressure, Carrier Proteins, Case-Control Studies, China, Female, Gelsolin, Gene Expression Regulation, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Hypertension, Male, Middle Aged, Phenotype, Polymorphism, Single Nucleotide, Receptor-Like Protein Tyrosine Phosphatases, Class 2, Risk Assessment, Risk Factors, Taiwan