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 Gui & 3 others Pak Chung Sham, Tai Hing Lam, Wen Harn Pan

Research output: Contribution to journalArticle

4 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 - 2014 Jan 1

Fingerprint

Genome-Wide Association Study
Taiwan
Hypertension
Gene Expression
Hong Kong
Genes
Single Nucleotide Polymorphism
Joints

All Science Journal Classification (ASJC) codes

  • Internal Medicine

Cite this

Chiang, Kuang Mao ; Yang, Hsin Chou ; Liang, Yu Jen ; Chen, Jaw Wen ; Hwang, Shiaw Min ; Ho, Hung Yun ; Ting, Chih Tai ; Lin, Tsung Hsien ; Sheu, Sheng Hsiung ; Tsai, Wei-Chuan ; Chen, Jyh Hong ; Leu, Hsin Bang ; Yin, Wei Hsian ; Chiu, Ting Yu ; Chen, Chin Iuan ; Lin, Shing Jong ; Thomas, G. Neil ; Tomlinson, Brian ; Guo, Youling ; Gui, Hong Sheng ; Sham, Pak Chung ; Lam, Tai Hing ; Pan, Wen Harn. / A three-stage genome-wide association study combining multilocus test and gene expression analysis for young-onset hypertension in Taiwan Han Chinese. In: American Journal of Hypertension. 2014 ; Vol. 27, No. 6. pp. 819-827.
@article{653caca71454418cbdccb57bd2193ad9,
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.",
author = "Chiang, {Kuang Mao} and Yang, {Hsin Chou} and Liang, {Yu Jen} and Chen, {Jaw Wen} and Hwang, {Shiaw Min} and Ho, {Hung Yun} and Ting, {Chih Tai} and Lin, {Tsung Hsien} and Sheu, {Sheng Hsiung} and Wei-Chuan Tsai and Chen, {Jyh Hong} and Leu, {Hsin Bang} and Yin, {Wei Hsian} and Chiu, {Ting Yu} and Chen, {Chin Iuan} and Lin, {Shing Jong} and Thomas, {G. Neil} and Brian Tomlinson and Youling Guo and Gui, {Hong Sheng} and Sham, {Pak Chung} and Lam, {Tai Hing} and Pan, {Wen Harn}",
year = "2014",
month = "1",
day = "1",
doi = "10.1093/ajh/hpt239",
language = "English",
volume = "27",
pages = "819--827",
journal = "American Journal of Hypertension",
issn = "0895-7061",
publisher = "Oxford University Press",
number = "6",

}

Chiang, KM, Yang, HC, Liang, YJ, Chen, JW, Hwang, SM, Ho, HY, Ting, CT, Lin, TH, Sheu, SH, Tsai, W-C, Chen, JH, Leu, HB, Yin, WH, Chiu, TY, Chen, CI, Lin, SJ, Thomas, GN, Tomlinson, B, Guo, Y, Gui, HS, Sham, PC, Lam, TH & Pan, WH 2014, 'A three-stage genome-wide association study combining multilocus test and gene expression analysis for young-onset hypertension in Taiwan Han Chinese', American Journal of Hypertension, vol. 27, no. 6, pp. 819-827. https://doi.org/10.1093/ajh/hpt239

A three-stage genome-wide association study combining multilocus test and gene expression analysis for young-onset hypertension in Taiwan Han Chinese. / Chiang, Kuang Mao; Yang, Hsin Chou; Liang, Yu Jen; Chen, Jaw Wen; Hwang, Shiaw Min; Ho, Hung Yun; Ting, Chih Tai; Lin, Tsung Hsien; Sheu, Sheng Hsiung; Tsai, Wei-Chuan; Chen, Jyh Hong; Leu, Hsin Bang; Yin, Wei Hsian; Chiu, Ting Yu; Chen, Chin Iuan; Lin, Shing Jong; Thomas, G. Neil; Tomlinson, Brian; Guo, Youling; Gui, Hong Sheng; Sham, Pak Chung; Lam, Tai Hing; Pan, Wen Harn.

In: American Journal of Hypertension, Vol. 27, No. 6, 01.01.2014, p. 819-827.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A three-stage genome-wide association study combining multilocus test and gene expression analysis for young-onset hypertension in Taiwan Han Chinese

AU - Chiang, Kuang Mao

AU - Yang, Hsin Chou

AU - Liang, Yu Jen

AU - Chen, Jaw Wen

AU - Hwang, Shiaw Min

AU - Ho, Hung Yun

AU - Ting, Chih Tai

AU - Lin, Tsung Hsien

AU - Sheu, Sheng Hsiung

AU - Tsai, Wei-Chuan

AU - Chen, Jyh Hong

AU - Leu, Hsin Bang

AU - Yin, Wei Hsian

AU - Chiu, Ting Yu

AU - Chen, Chin Iuan

AU - Lin, Shing Jong

AU - Thomas, G. Neil

AU - Tomlinson, Brian

AU - Guo, Youling

AU - Gui, Hong Sheng

AU - Sham, Pak Chung

AU - Lam, Tai Hing

AU - Pan, Wen Harn

PY - 2014/1/1

Y1 - 2014/1/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84900849365&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84900849365&partnerID=8YFLogxK

U2 - 10.1093/ajh/hpt239

DO - 10.1093/ajh/hpt239

M3 - Article

VL - 27

SP - 819

EP - 827

JO - American Journal of Hypertension

JF - American Journal of Hypertension

SN - 0895-7061

IS - 6

ER -