New Heart Disease Risk Genes Point to Flaws in Blood Vessel Walls

Newswise — PHILADELPHIA - Coronary artery disease (CAD) is a leading cause of death worldwide. Despite dozens of regions in the genome associated with CAD, most of the genetic components of heart diseases are not fully understood, suggesting that more genes are out there to be found. A team led by researchers from the Perelman School of Medicine at the University of Pennsylvania, Stanford University, and Cambridge University found 15 new risk genes for coronary artery disease. They published their results online this week in Nature Genetics.

They studied genetic variants across the genome in 250,736 participants in total, including 88,192 patients with CAD, and identified 15 new risk genes providing new insights about the cause of CAD. Overall they found that many of these risk genes are associated with the myriad of functions taking place in cells lining blood vessels, blood clotting, inflammation and how cells bind with each other.

“Coronary artery disease tends to cluster in families and has a strong genetic basis; however, we do not fully understand its genetic basis,” said senior author Danish Saleheen, PhD, an assistant professor of Epidemiology and Biostatistics at Penn. “We conducted the largest genetic analyses on coronary artery disease to date, including analyses of people of European, African, South Asian, and East Asian heritages.”

The team identified the new genetic CAD associations via SNPs -- or single-nucleotide polymorphisms, places in genes in which the DNA building blocks differ from person to person by only one block, or nucleotide. They found CAD-related SNPs in or near genes governing such pathways as stickiness of cells, coagulation and inflammation, and the differentiation of smooth muscle cells.

“Next we aim to identify the exact biological mechanisms at these 15 novel sites in the genome that lead to development of CAD,” Saleheen said. “Greater understanding of such pathways should ultimately lead to development of new therapies for CAD.”

Saleheen has received support from the National Heart, Lung, and Blood Institute (RC2HL101834, RC1TW008485), the NIH Fogarty International Center (RC1TW008485), Pfizer, Genentech, Regeneron Pharmaceuticals, and Eli Lilly.

Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $6.7 billion enterprise.

The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 20 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $392 million awarded in the 2016 fiscal year.

The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center -- which are recognized as one of the nation's top "Honor Roll" hospitals by U.S. News & World Report -- Chester County Hospital; Lancaster General Health; Penn Wissahickon Hospice; and Pennsylvania Hospital -- the nation's first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2016, Penn Medicine provided $393 million to benefit our community.