A multiomics study by Adriana Hung, Todd Edwards and colleagues provides new insight into the genetic basis of blood pressure (BP) traits. “This work was motivated by important advances in… Click to show full abstract
A multiomics study by Adriana Hung, Todd Edwards and colleagues provides new insight into the genetic basis of blood pressure (BP) traits. “This work was motivated by important advances in the field that have enabled genetic investigations to be more comprehensive, including the availability of large cohorts and tissuespecific reference panels of gene expression,” explains Hung. First, the researchers performed a genomewide association study (GWAS) of data from the Million Veteran Program (MVP) and the United Kingdom Biobank with independent replication in other large cohorts. These analyses, which included data from >750,000 individuals, identified 208 novel common singlenucleotide polymorphisms (SNPs) and 53 novel rare variants that were associated with BP traits. To evaluate the relationship between genetically predicted gene expression (GPGE) levels and BP traits, the researchers conducted a transcriptomewide association analysis using the SPrediXcan method. They identified >4,000 BP associations with predicted expression of 840 genes in 45 tissues. A phenomewide association study of BP genetic risk scores in the MVP cohort showed that the effects of common SNPs on BP were consistent between ethnic groups. The researchers also analysed the GPGE data to identify gene–drug relationships. “We found 41 potential novel gene targets for BP treatment and 289 gene targets for existing drugs that could potentially be repurposed as antihypertensives, including several drugs that target kidney BP genes,” says Edwards. In addition, they used singlecell sequencing of mouse kidney cells to investigate the expression of homologues of genes that were identified as significant in the SPrediXcan analysis of kidney tissue. “We observed evidence that tubules are the key structures in the kidney that mediate genetic influences on BP,” comments Edwards. The researchers are now conducting a much larger transethnic GWAS of BP traits that includes additional data from East Asian and Eastern European populations. Ellen F. Carney g E N E t I c S
               
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