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Mount Sinai study identifies new gene variations associated with heart rate

Findings pinpoint 14 genetic targets in humans that may provide insight for the treatment of cardiovascular disease

2013-04-15
(Press-News.org) (New York, NY – April 14, 2013) – Through a collaborative genome-wide study on individuals, researchers have discovered 14 new genetic variations that are associated with heart rate. Since heart rate is a marker of cardiovascular health, these findings could provide a better understanding of genetic regulation of heart beat and is a first step towards identifying targets for new drugs to treat cardiovascular disease.

The study, titled, "Identification of Heart Rate-Associated Loci and Their Effects on Cardiac Conduction and Rhythm Disorders," was published online this week in the April issue of Nature Genetics. Led by researchers at the Icahn School of Medicine at Mount Sinai and the Medical Research Council Epidemiology Unit in Cambridge, UK, the collaboration involved 268 researchers from 211 institutions, as well as six large research consortia joined forces.

In order to gain new insights into the genetic regulation of heart rate, Dr. Ruth Loos, Director of the Genetics of Obesity and Related Metabolic Traits Program at the Charles Bronfman Institute for Personalized Medicine at Mount Sinai and honorary investigator at the Medical Research Council Epidemiology Unit and her team, spent three years working on a genome-wide association study using data from 181,171 participants from 65 studies during 2009-2012. "Without any prior hypothesis, we studied the entire human genome hoping to identify new genetic variations that no one before had even imagined would play a role in the regulation of heart rate," said Dr. Loos, senior author of the study. "This discovery is just the beginning of something new and exciting and can hopefully be used to identify new drugs that can be used for the treatment of heart rhythm disorders."

In a follow-up study, experimental down-regulation of gene expression was then conducted on fruit flies and zebra fish, to better understand how genetic variations might affect heart rate. These experiments identified 20 genes with a role in heart rate regulation, signal transmission, embryonic development of the heart, as well as cardiac disorders, such as dilated cardiomyopathy, congenital heart failure and sudden heart failure. "Our findings in humans as well as in fruit flies and zebrafish provide new insights into mechanisms that regulate heart rate," said Dr. Marcel den Hoed, post-doctoral fellow at the Medical Research Council Epidemiology Unit and lead author of the study.

The follow-up study also showed that a genetic susceptibility for higher heart rate is associated with altered cardiac conduction and a reduced risk of sick sinus syndrome, a common indicator for pacemaker implantation. "Our study tripled the number of genetic variations that are known to be associated with heart rate, some of which are also associated with other cardiovascular risk factors and with heart rhythm disorder," said Dr. Loos.

### About The Charles Bronfman Institute for Personalized Medicine

The Charles Bronfman Institute for Personalized Medicine (IPM) drives innovation in the data-driven and gene-based individualization of healthcare. The Institute's groundbreaking work led to the creation of the BioMeBiobank Program to enable innovation in personalized healthcare. Over 23,000 Mount Sinai patients have enrolled in the BioMe program, which helps them receive more targeted, personalized care in real-time – based on their own DNA – through Mount Sinai's electronic medical record (EMR) system. The EMR-linked personalized medicine system empowers participating BioMe patients by providing tailored information in data-driven, gene-based personalized healthcare. This information includes each enrolled patient's unique genetic information and clinical data.

Mount Sinai patients who enroll in the BioMe program also contribute to medical breakthroughs by consenting to make their DNA, genetic and clinical information available for medical research in a secure and de-identified manner.

IPM also provides participating healthcare professionals with education, tools and resources for up-to-date practice guidelines incorporating the latest gene-based information for personalized healthcare.

For more information, visit http://icahn.mssm.edu/research/institutes/institute-for-personalized-medicine

About The Mount Sinai Medical Center

The Mount Sinai Medical Center encompasses both The Mount Sinai Hospital and Icahn School of Medicine at Mount Sinai. Established in 1968, the Icahn School of Medicine at Mount Sinai is one of the leading medical schools in the United States. The Icahn School of Medicine is noted for innovation in education, biomedical research, clinical care delivery, and local and global community service. It has more than 3,400 faculty members in 32 departments and 14 research institutes, and ranks among the top 20 medical schools both in National Institutes of Health (NIH) funding and by U.S. News & World Report.

The Mount Sinai Hospital, founded in 1852, is a 1,171-bed tertiary- and quaternary-care teaching facility and one of the nation's oldest, largest and most-respected voluntary hospitals. In 2012, U.S. News & World Report ranked The Mount Sinai Hospital 14th on its elite Honor Roll of the nation's top hospitals based on reputation, safety, and other patient-care factors. Mount Sinai is one of just 12 integrated academic medical centers whose medical school ranks among the top 20 in NIH funding and by U.S. News & World Report and whose hospital is on the U.S. News & World Report Honor Roll. Nearly 60,000 people were treated at Mount Sinai as inpatients last year, and approximately 560,000 outpatient visits took place.

For more information, visit http://www.mountsinai.org/. Find Mount Sinai on: Facebook: http://www.facebook.com/mountsinainyc
Twitter @mountsinainyc
YouTube: http://www.youtube.com/mountsinainy END


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[Press-News.org] Mount Sinai study identifies new gene variations associated with heart rate
Findings pinpoint 14 genetic targets in humans that may provide insight for the treatment of cardiovascular disease