A genome-wide association study of essential hypertension in an Australian population using a DNA pooling approach
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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 χ 2 test. 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.
KeywordsEssential hypertension Genome-wide association study Pooled DNA NFKB1 GLI2
We would like to thank Stuart MacGregor at QIMR for valuable advice and assistance with the analysis of GWAS data. J. Fowdar has been funded by an Endeavour International Postgraduate Research Scholarship (EIPRS) and a Griffith University Postgraduate Research Scholarship (GUPRS). Yi Lu is supported by the NHMRC early career fellowship (CJ-Martin overseas fellowship). This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors; however, sample collection was supported by grants from the National Health and Medical Research Council (NHMRC), Gemini Genomics UK Limited, Cambridge, UK, and Griffith University funding support.
Compliance with ethical standards
The study protocol was approved by the Griffith University’s Human Research Ethics Committee (HSC/18/04/HREC) and all procedures complied with the current ethical standards for human research in Australia, including the provision of informed consent to all participants.
Conflict of interest
The authors declare no conflict of interest.
Informed consent was obtained from all individual participants included in this study.
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