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

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, G. Neil Thomas, Brian Tomlinson, Youling Guo, Hong Sheng GuiPak Chung Sham, Tai Hing Lam, Wen Harn Pan

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14 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)819-827
Number of pages9
JournalAmerican Journal of Hypertension
Volume27
Issue number6
DOIs
Publication statusPublished - Jun 2014
Externally publishedYes

ASJC Scopus Subject Areas

  • Internal Medicine

Keywords

  • blood pressure
  • gene expression
  • genome-wide association study
  • Han Chinese
  • hypertension
  • multilocus test
  • single nucleotide polymorphisms
  • young-onset hypertension

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