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A three-stage genome-wide association study combining multilocus test and gene expression analysis for young-onset hypertension in Taiwan Han Chinese.
- Source :
-
American journal of hypertension [Am J Hypertens] 2014 Jun; Vol. 27 (6), pp. 819-27. Date of Electronic Publication: 2014 Jan 11. - Publication Year :
- 2014
-
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.<br />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.<br />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.<br />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.
- Subjects :
- Actinin genetics
Adult
Age of Onset
Carrier Proteins genetics
Case-Control Studies
China ethnology
DNA-Binding Proteins
Female
Gelsolin genetics
Gene Expression Regulation
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Hypertension ethnology
Hypertension physiopathology
Male
Middle Aged
Phenotype
Polymorphism, Single Nucleotide
Receptor-Like Protein Tyrosine Phosphatases, Class 2 genetics
Risk Assessment
Risk Factors
Taiwan epidemiology
Asian People genetics
Blood Pressure genetics
Genetic Loci
Hypertension genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1941-7225
- Volume :
- 27
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- American journal of hypertension
- Publication Type :
- Academic Journal
- Accession number :
- 24413707
- Full Text :
- https://doi.org/10.1093/ajh/hpt239