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 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.
Institute of Statistical Science, Academia Sinica, Taipei, Taiwan.
Hsin-Chou
HC
Yang
Yu-Jen
YJ
Liang
Yi-Lin
YL
Wu
Chia-Min
CM
Chung
Kuang-Mao
KM
Chiang
Hung-Yun
HY
Ho
Chih-Tai
CT
Ting
Tsung-Hsien
TH
Lin
Sheng-Hsiung
SH
Sheu
Wei-Chuan
WC
Tsai
Jyh-Hong
JH
Chen
Hsin-Bang
HB
Leu
Wei-Hsian
WH
Yin
Ting-Yu
TY
Chiu
Chin-Iuan
CI
Chen
Cathy S J
CS
Fann
Jer-Yuarn
JY
Wu
Teng-Nan
TN
Lin
Shing-Jong
SJ
Lin
Yuan-Tsong
YT
Chen
Jaw-Wen
JW
Chen
Wen-Harn
WH
Pan
D000328:Adult; D017668:Age of Onset; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000235:genetics; D005136:Eye Proteins / Q000235:genetics; D005260:Female; D015894:Genome, Human; D055106:Genome-Wide Association Study; D005838:Genotype; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics; D006801:Humans; D006973:Hypertension / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011509:Proteoglycans / Q000235:genetics; D013624:Taiwan / Q000453:epidemiology; D055815:Young Adult; D020663:ras Guanine Nucleotide Exchange Factors
D016326:Extracellular Matrix Proteins; D005136:Eye Proteins; D020662:Guanine Nucleotide Exchange Factors; C486428:IMPG1 protein, human; D011509:Proteoglycans; C413212:RASGRP3 protein, human; D020663:ras Guanine Nucleotide Exchange Factors