Type

Journal Article

Authors

Alice V Stanton
Nilesh J Samani
Maciej Tomaszewski
Nicholas Masca
Patricia B Munroe
Eoin O'Brien
Praveen Surendran
Kevin V Shianna
Norman Delanty
Gianpiero L Cavalleri
and 2 others

Subjects

Psychiatry

Topics
follow up genome wide association studies ion channel single nucleotide polymorphisms community based gene loci blood pressure candidate gene

Two further blood pressure loci identified in ion channel genes with a gene-centric approach. (2014)

Abstract Blood pressure (BP) is highly heritable, but our understanding of the genetic causes underlying variations in BP is incomplete. In this study, we explored whether novel loci associated with BP could be identified using a genecentric approach in 3 community-based cohorts with accurate BP measurements. Genotyping of 1857 single nucleotide polymorphisms (SNPs) in 91 ion channel genes was performed in a discovery cohort (n=358). Thirty-four SNPs associated with BP traits (P≤0.01) were followed up in an independent population (n=387); significant SNPs from this analysis were looked up in another independent population (n=1010) and meta-analyzed. Repeated clinic and ambulatory measurements were available for all but the discovery cohort (clinic only). Association analyses were performed, with systolic, diastolic, and pulse pressures as quantitative traits, adjusting for age and sex. Quantile-quantile plots indicated that the genecentric approach resulted in an inflation of association signals. Of the 29 SNPs taken forward from the discovery cohort, 2 SNPs were associated with BP phenotypes with the same direction of effect, with experiment-wide significance, in follow-up cohort I. These were rs2228291, in the chloride channel gene CLCN2, and rs10513488, in the potassium channel gene KCNAB1. Both associations were subsequently replicated in follow-up cohort II. Using a genecentric design and 3 well-phenotyped populations, this study identified 2 previously unreported, biologically plausible, genetic associations with BP. These results suggest that dense genotyping of genes, in pathways known to influence BP, could add to candidate-gene and Genome Wide Association studies in further explaining BP heritability.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

Alice V Stanton, Nilesh J Samani, Maciej Tomaszewski, Nicholas Masca, Patricia B Munroe, Eoin O'Brien, Praveen Surendran, Kevin V Shianna, Norman Delanty, Gianpiero L Cavalleri and 2 others

Experts in our system

1
Alice Stanton
Royal College of Surgeons in Ireland
Total Publications: 44
 
2
Eoin O'Brien
University College Dublin
Total Publications: 75
 
3
Praveen Surendran
Royal College of Surgeons in Ireland
Total Publications: 4
 
4
Norman Delanty
Royal College of Surgeons in Ireland
Total Publications: 41
 
5
Gianpiero L Cavalleri
Royal College of Surgeons in Ireland
Total Publications: 35