A genome-wide association study of essential hypertension in an Australian population using a DNA pooling approach.
Mol Genet Genomics
; 292(2): 307-324, 2017 Apr.
Article
de En
| MEDLINE
| ID: mdl-27866268
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 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.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Étude d'association pangénomique
/
Hypertension artérielle
Type d'étude:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limites:
Female
/
Humans
/
Male
Pays/Région comme sujet:
Oceania
Langue:
En
Journal:
Mol Genet Genomics
Sujet du journal:
BIOLOGIA MOLECULAR
/
GENETICA
Année:
2017
Type de document:
Article
Pays d'affiliation:
Australie