Study in Nature Genetics identifies six new variants.

Scientists have associated variants in eight regions of DNA with blood pressure levels in humans. Of the identified regions, six have not previously been implicated in blood pressure regulation.

In their study, receiving advance online publication in Nature Genetics, members of the Global Blood Pressure Genetics (Global BPgen) consortium, which includes 159 investigators from 93 centers in the U.S. and Europe, analyzed genetic data from up to 130,000 individuals from around the world.

To get a study sample large enough to detect gene variants with modest effects, Global BPgen researchers conducted a meta-analysis of 17 genome-wide association studies that included measurements of participants’ blood pressure. Analysis of 2.5 million DNA sequence variants in more than 34,000 individuals of European ancestry identified several chromosomal regions where genes influencing blood pressure appeared to be located.

To confirm the results of the first-stage meta-analysis, two additional analyses were done. The researchers genotyped the 12 gene variants with the strongest signals in more than 71,000 additional individuals of European descent and in 12,300 people of Indian-Asian ancestry. They also exchanged their top results with consortium investigators called Cohorts for Heart and Aging Research in Genomic Epidemeology.

Combining the results of all three analyses identified eight gene regions associated with both systolic and diastolic blood pressure and with the risk of hypertension. One region includes genes for two natriuretic peptides, proteins known to relax blood vessels and control sodium excretion by the kidneys. Earlier this year, another team found that variations in these proteins influence blood pressure. Another region identified in the current study is known to contain a gene involved in a rare familial form of hypertension.

Changes in one gene, ATP2B1, were linked to both blood pressure and hypertension. The gene ATP2B1 makes a protein that pumps calcium out of the cells that line the interior of blood vessels. Changes in SH2B3, a protein involved in the immune response, were also linked to increased blood pressure. Researchers also identified changes in genes involved in cell growth as well as genes necessary for proper heart development.

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