Contributions of rare coding variants in hypotension syndrome genes to population blood pressure variation.

TitleContributions of rare coding variants in hypotension syndrome genes to population blood pressure variation.
Publication TypeJournal Article
Year of Publication2018
AuthorsNandakumar, P, Morrison, AC, Grove, ML, Boerwinkle, E, Chakravarti, A
JournalMedicine (Baltimore)
Date Published2018 Aug
KeywordsBlack People, Blood Pressure, Exome Sequencing, Female, Genetic Predisposition to Disease, Genetic Variation, Humans, Hypertension, Hypotension, Male, Middle Aged, Phenotype, Potassium Channels, Inwardly Rectifying, Prospective Studies, Reproducibility of Results, Risk Factors, Solute Carrier Family 12, Member 1, Solute Carrier Family 12, Member 3, White People

Rare variants, in particular renal salt handling genes, contribute to monogenic forms of hypertension and hypotension syndromes with electrolyte abnormalities. A study by Ji et al (2008) demonstrated this effect for rare loss-of-function coding variants in SLC12A3 (NCCT), SLC12A1 (NKCC2), and KCNJ1 (ROMK) that led to reduction of ∼6 mm Hg for SBP and ∼3 mm Hg for DBP among carriers in 2492 European ancestry Framingham Heart Study (FHS) subjects. These findings support a potentially large role for these variants in interindividual variation in systolic and diastolic blood pressure (SBP, DBP) in the population. The present study focuses on replicating the analyses completed by Ji et al to identify effects of rare variants in the population-based Atherosclerosis Risk in Communities (ARIC) study.We attempted to replicate the findings by Ji et al by applying their criteria to identify putative loss-of-function variants with allele frequency

Alternate JournalMedicine (Baltimore)
PubMed ID30113482
PubMed Central IDPMC6113003
Grant ListR01 HL086694 / HL / NHLBI NIH HHS / United States

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