Genome-wide association study of young-onset hypertension in the Han Chinese population of Taiwan.

Young-onset hypertension has a stronger genetic component than late-onset counterpart; thus, the identification of genes related to its susceptibility is a critical issue for the prevention and management of this disease. We carried out a two-stage association scan to map young-onset hypertension su...

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Autores principales: Hsin-Chou Yang, Yu-Jen Liang, Yi-Lin Wu, Chia-Min Chung, Kuang-Mao Chiang, 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, Cathy S J Fann, Jer-Yuarn Wu, Teng-Nan Lin, Shing-Jong Lin, Yuan-Tsong Chen, Jaw-Wen Chen, Wen-Harn Pan
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Publicado: Public Library of Science (PLoS) 2009
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Acceso en línea:https://doaj.org/article/0cc974ab089946af90b2d94b4f5b7597
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spelling oai:doaj.org-article:0cc974ab089946af90b2d94b4f5b75972021-11-25T06:22:49ZGenome-wide association study of young-onset hypertension in the Han Chinese population of Taiwan.1932-620310.1371/journal.pone.0005459https://doaj.org/article/0cc974ab089946af90b2d94b4f5b75972009-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19421330/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Young-onset hypertension has a stronger genetic component than late-onset counterpart; thus, the identification of genes related to its susceptibility is a critical issue for the prevention and management of this disease. We carried out a two-stage association scan to map young-onset hypertension susceptibility genes. The first-stage analysis, a genome-wide association study, analyzed 175 matched case-control pairs; the second-stage analysis, a confirmatory association study, verified the results at the first stage based on a total of 1,008 patients and 1,008 controls. Single-locus association tests, multilocus association tests and pair-wise gene-gene interaction tests were performed to identify young-onset hypertension susceptibility genes. After considering stringent adjustments of multiple testing, gene annotation and single-nucleotide polymorphism (SNP) quality, four SNPs from two SNP triplets with strong association signals (-log(10)(p)>7) and 13 SNPs from 8 interactive SNP pairs with strong interactive signals (-log(10)(p)>8) were carefully re-examined. The confirmatory study verified the association for a SNP quartet 219 kb and 495 kb downstream of LOC344371 (a hypothetical gene) and RASGRP3 on chromosome 2p22.3, respectively. The latter has been implicated in the abnormal vascular responsiveness to endothelin-1 and angiotensin II in diabetic-hypertensive rats. Intrinsic synergy involving IMPG1 on chromosome 6q14.2-q15 was also verified. IMPG1 encodes interphotoreceptor matrix proteoglycan 1 which has cation binding capacity. The genes are novel hypertension targets identified in this first genome-wide hypertension association study of the Han Chinese population.Hsin-Chou YangYu-Jen LiangYi-Lin WuChia-Min ChungKuang-Mao ChiangHung-Yun HoChih-Tai TingTsung-Hsien LinSheng-Hsiung SheuWei-Chuan TsaiJyh-Hong ChenHsin-Bang LeuWei-Hsian YinTing-Yu ChiuChin-Iuan ChenCathy S J FannJer-Yuarn WuTeng-Nan LinShing-Jong LinYuan-Tsong ChenJaw-Wen ChenWen-Harn PanPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 4, Iss 5, p e5459 (2009)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Hsin-Chou Yang
Yu-Jen Liang
Yi-Lin Wu
Chia-Min Chung
Kuang-Mao Chiang
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
Cathy S J Fann
Jer-Yuarn Wu
Teng-Nan Lin
Shing-Jong Lin
Yuan-Tsong Chen
Jaw-Wen Chen
Wen-Harn Pan
Genome-wide association study of young-onset hypertension in the Han Chinese population of Taiwan.
description Young-onset hypertension has a stronger genetic component than late-onset counterpart; thus, the identification of genes related to its susceptibility is a critical issue for the prevention and management of this disease. We carried out a two-stage association scan to map young-onset hypertension susceptibility genes. The first-stage analysis, a genome-wide association study, analyzed 175 matched case-control pairs; the second-stage analysis, a confirmatory association study, verified the results at the first stage based on a total of 1,008 patients and 1,008 controls. Single-locus association tests, multilocus association tests and pair-wise gene-gene interaction tests were performed to identify young-onset hypertension susceptibility genes. After considering stringent adjustments of multiple testing, gene annotation and single-nucleotide polymorphism (SNP) quality, four SNPs from two SNP triplets with strong association signals (-log(10)(p)>7) and 13 SNPs from 8 interactive SNP pairs with strong interactive signals (-log(10)(p)>8) were carefully re-examined. The confirmatory study verified the association for a SNP quartet 219 kb and 495 kb downstream of LOC344371 (a hypothetical gene) and RASGRP3 on chromosome 2p22.3, respectively. The latter has been implicated in the abnormal vascular responsiveness to endothelin-1 and angiotensin II in diabetic-hypertensive rats. Intrinsic synergy involving IMPG1 on chromosome 6q14.2-q15 was also verified. IMPG1 encodes interphotoreceptor matrix proteoglycan 1 which has cation binding capacity. The genes are novel hypertension targets identified in this first genome-wide hypertension association study of the Han Chinese population.
format article
author Hsin-Chou Yang
Yu-Jen Liang
Yi-Lin Wu
Chia-Min Chung
Kuang-Mao Chiang
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
Cathy S J Fann
Jer-Yuarn Wu
Teng-Nan Lin
Shing-Jong Lin
Yuan-Tsong Chen
Jaw-Wen Chen
Wen-Harn Pan
author_facet Hsin-Chou Yang
Yu-Jen Liang
Yi-Lin Wu
Chia-Min Chung
Kuang-Mao Chiang
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
Cathy S J Fann
Jer-Yuarn Wu
Teng-Nan Lin
Shing-Jong Lin
Yuan-Tsong Chen
Jaw-Wen Chen
Wen-Harn Pan
author_sort Hsin-Chou Yang
title Genome-wide association study of young-onset hypertension in the Han Chinese population of Taiwan.
title_short Genome-wide association study of young-onset hypertension in the Han Chinese population of Taiwan.
title_full Genome-wide association study of young-onset hypertension in the Han Chinese population of Taiwan.
title_fullStr Genome-wide association study of young-onset hypertension in the Han Chinese population of Taiwan.
title_full_unstemmed Genome-wide association study of young-onset hypertension in the Han Chinese population of Taiwan.
title_sort genome-wide association study of young-onset hypertension in the han chinese population of taiwan.
publisher Public Library of Science (PLoS)
publishDate 2009
url https://doaj.org/article/0cc974ab089946af90b2d94b4f5b7597
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