title: A genome-wide association study of essential hypertension in an Australian population using a DNA pooling approach.
abstract: Despite the success of genome-wide association studies (GWAS) in detecting genetic loci involved in complex traits, few susceptibility genes have been detected for essential hypertension (EH). We aimed to use pooled DNA GWAS approach to identify and validate novel genomic loci underlying EH susceptibility in an Australian case-control population. Blood samples and questionnaires detailing medical history, blood pressure, and prescribed medications were collected for 409 hypertensives and 409 age-, sex- and ethnicity-matched normotensive controls. Case and control DNA were pooled in quadruplicate and hybridized to Illumina 1 M-Duo arrays. Allele frequencies agreed with those reported in reference data and known EH association signals were represented in the top-ranked SNPs more frequently than expected by chance. Validation showed that pooled DNA GWAS gave reliable estimates of case and control allele frequencies. Although no markers reached Bonferroni-corrected genome-wide significance levels (5.0 × 10-8), the top marker rs34870220 near ASGR1 approached significance (p = 4.32 × 10-7), as did several candidate loci (p < 1 × 10-6) on chromosomes 2, 4, 6, 9, 12, and 17. Four markers (located in or near genes NHSL1, NKFB1, GLI2, and LRRC10) from the top ten ranked SNPs were individually genotyped in pool samples and were tested for association between cases and controls using the χ2test. Of these, rs1599961 (NFKB1) and rs12711538 (GLI2) showed significant difference between cases and controls (p < 0.01). Additionally, four top-ranking markers within NFKB1 were found to be in LD, suggesting a single strong association signal for this gene.
authors.affiliation: School of Medical Science, Griffith University, Gold Coast, Australia.
authors.forename: Javed Y
authors.initials: JY
authors.lastname: Fowdar
authors.affiliation: School of Medical Science, Griffith University, Gold Coast, Australia.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Grealy
authors.affiliation: Genetic Epidemiology Department, Queensland Institute of Medical Research, Brisbane, Australia.
authors.forename: Yi
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Genomics Research Centre, Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Queensland University of Technology, 60 Musk Ave, Kelvin Grove, Brisbane, QLD, 4059, Australia. lyn.griffiths@qut.edu.au.
authors.forename: Lyn R
authors.initials: LR
authors.lastname: Griffiths
mesh_terms: D001315:Australia; D016022:Case-Control Studies; D002874:Chromosome Mapping; D000075222:Essential Hypertension; D005006:Ethnicity; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D051741:Kruppel-Like Transcription Factors / Q000235:genetics; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D052002:NF-kappa B p50 Subunit / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D009693:Nucleic Acid Hybridization; D011786:Quality Control; D017422:Sequence Analysis, DNA; D011795:Surveys and Questionnaires; D000075746:Zinc Finger Protein Gli2
chemical_list: C082593:GLI2 protein, human; D005819:Genetic Markers; D051741:Kruppel-Like Transcription Factors; D052002:NF-kappa B p50 Subunit; C489548:NFKB1 protein, human; D009687:Nuclear Proteins; D000075746:Zinc Finger Protein Gli2
keywords: Essential hypertension; GLI2; Genome-wide association study; NFKB1; Pooled DNA