title: Beyond genome-wide association studies: new strategies for identifying genetic determinants of hypertension.
abstract: Genetic linkage and association methods have long been the most important tools for gene identification in humans. These approaches can either be hypothesis-based (i.e., candidate-gene studies) or hypothesis-free (i.e., genome-wide studies). The first part of this review offers an overview of the latest successes in gene finding for blood pressure (BP) and essential hypertension using these DNA sequence-based discovery techniques. We further emphasize the importance of post-genome-wide association study (post-GWAS) analysis, which aims to prioritize genetic variants for functional follow-up. Whole-genome next-generation sequencing will eventually be necessary to provide a more comprehensive picture of all DNA variants affecting BP and hypertension. The second part of this review discusses promising novel approaches that move beyond the DNA sequence and aim to discover BP genes that are differentially regulated by epigenetic mechanisms, including microRNAs, histone modification, and methylation.
authors.affiliation: Georgia Prevention Institute, Department of Pediatrics, Medical College of Georgia, Augusta, GA, USA. xwang@georgiahealth.edu
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Wang
authors.forename: Bram P
authors.initials: BP
authors.lastname: Prins
authors.forename: Siim
authors.initials: S
authors.lastname: Sõber
authors.forename: Maris
authors.initials: M
authors.lastname: Laan
authors.forename: Harold
authors.initials: H
authors.lastname: Snieder
mesh_terms: D001794:Blood Pressure; D044127:Epigenesis, Genetic; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D006973:Hypertension / Q000453:epidemiology / Q000235:genetics*; D035683:MicroRNAs; D020641:Polymorphism, Single Nucleotide; D013997:Time Factors; D014481:United States / Q000453:epidemiology
chemical_list: D035683:MicroRNAs