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New insights into the biological processes related to the electrical activity of the heart have been obtained through a major scientific study on the genome. The research had the largest sample size of a project of this type.
The molecular mechanisms explored in this study provide insights into cardiac electrical diseases and may suggest ways to research drugs to prevent and treat heart rhythm or conduction problems. The recent cardiac genomics project involved more than 125 researchers in several institutions around the world. The results appear this week in Nature Communications .
Members of the Cardiovascular Health Research Unit of the University of Washington Dr. Nona Sotoodehnia, Laughlin Professor of Medicine, Division of Cardiology, and Sina A. Gharib, Associate Professor of Medicine, Division of Lung Care, Intensive Care and Sleep Medicine, both at the School of Medicine at the University of Washington in Seattle, were among the five scientific supervisors of the international study. Dr. Jessica van van Setten from the University of Utrecht, the Netherlands, was the principal author of the published study document.
The researchers were particularly interested in the part of the electrocardiogram, or cardiac recording, called the PR interval. 19659003] In general, the PR interval, measured in milliseconds, traces the electrical conduction of the sinus node of the heart through the atria to its ventricles.
The sinus node is the pacemaker of the heart. Atria are the two smallest upper heart chambers that collect blood from the body and prime the pump. The ventricles are the two largest left and right lower chambers that collect and pump blood to the rest of the body.
The PR interval triggers the onset of contraction of atria. The PR interval ends when the ventricles are prepared to push the blood.
Previous studies in twins and in families suggest that the heritability of the PR interval is between 40% and 60%. This large multi-ethnic study has allowed researchers to identify the genes and processes involved in atrial conduction. These results extended what was known biologically and clinically from previous research.
The researchers conducted a genome-wide badociation study of more than 92,000 individuals of European origin. Genome-wide badociation studies are projects that examine the DNA of different individuals to find genetic variations that could be badociated with a particular trait or disease.
In this study, millions of genetic markers were examined in the genome. with atrial conduction.
Study researchers identified 44 chromosomal regions linked to the PR interval. "The genes in these 44 loci are overrepresented in the processes of heart disease, including heart block, sinus syndrome and atrial fibrillation," the researchers wrote.
Atrial fibrillation is an abnormal heart rhythm that can increase the risk of heart failure and sudden death. It also increases the risk of clots forming in the heart and moving around the brain to cause a stroke. Heart block is an interference with the electric waves that fuel the movement of the heart. She, and other conduction defects, sometimes require pacemaker implantation.
Additional badyzes, using various or combined methods, were carried out by examining more than 105,000 people of African and European descent. These provided six additional loci related to the atrial or atrioventricular electrical activities of the heart
. The results revealed a number of different processes involved in atrial and atrioventricular conduction. The developmental pathways in the heart, especially the formation of the chambers and the development of the system that allows the conduction of the electrical signal through the heart, have been involved in the origin of these kinds of heart diseases.
channel genes, and the cellular junction or cell signaling proteins involved in the conduction of electrical waves of the heart also showed possible contributions to abnormalities.
The researchers also discovered gene regulators that were found only in the atrial tissues of the heart. This observation, they noted, highlights the reason for examining some genomic data in tissue types relevant to the disease or trait in question, not just in blood samples. In contrast, the researchers also observed overlapping factors that influenced the formation of blood and heart vessels.
In addition, the researchers performed trans-ethnic badyzes that showed that a majority of the genetic badociations found in the European population were also present in the study. African-American population. They nevertheless pointed out that there were some remarkable interethnic differences.
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