Genome-wide association studies will unlock the genetic basis of hypertension: pro side of the argument.
This brief commentary is based on the debate that took part in May 2010 in New York. We describe the initial difficulties experienced in early genome-wide association studies of blood pressure and hypertension, as well as strategic developments, including large meta-analyses and sampling from the extremes of blood pressure distribution. The reasons for negative attitudes toward the genome-wide association studies include their nonhypothesis-driven character and the need for very large sample sizes. Nevertheless, we describe published successes, which include 13 single nucleotide polymorphisms/loci associated with blood pressure and hypertension at P < 5 x 10⁻⁸, which fulfill the criteria of genome-wide significance. We conclude by suggesting a way forward, which will include resequencing to aid fine mapping and the identification of causal variants, even bigger meta-analyses, and, most importantly, appropriate functional studies leading to clinically useful applications.
Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary, and Life Sciences, University of Glasgow, Glasgow, UK. ad7e@clinmed.gla.ac.uk
Anna F
AF
Dominiczak
Patricia B
PB
Munroe
D001794:Blood Pressure / Q000235:genetics; D002874:Chromosome Mapping; D056426:Genetic Loci; D055106:Genome-Wide Association Study; D006801:Humans; D006973:Hypertension / Q000453:epidemiology / Q000235:genetics*; D015201:Meta-Analysis as Topic; D020641:Polymorphism, Single Nucleotide; D018401:Sample Size