Researchers at Washington University School of Medicine in St. Louis have received an $8 million grant to investigate the genetic and environmental roots of cardiovascular disease risk factors. The four-year grant will support the first large-scale, multiethnic statistical analysis of risk factors for cardiovascular disease that looks at lifestyle interactions with genes.
The investigators will use existing data from over 30 studies, which include detailed genetic data, measures of cardiovascular risk factors — namely, blood pressure and cholesterol levels — as well as information on lifestyle, including smoking, alcohol consumption, physical activity, socioeconomic status and diet.
To carry out this type of study, large numbers of subjects are needed to have sufficient power to detect interactions of genes and lifestyle.
As such, the study represents a massive international collaboration that will bring together data on more than 300,000 subjects from various ethnically diverse groups, including people of European, African, Hispanic and Asian descent. According to the researchers, this allows a broad view of interactions and how they play out in populations with different genetic and cultural histories.
“This study is unprecedented in many ways,” said principal investigator D.C. Rao, PhD, professor of biostatistics, genetics, psychiatry and mathematics and director of the Division of Biostatistics. “Other researchers have done analyses that look at interactions of genes and lifestyle in cardiovascular disease but not on this scale.
“We have compelling preliminary data that highlight the potential of these investigations,” he said. “We found, for example, several novel genes associated with high blood pressure that were not previously known until the interactions with alcohol consumption or education were brought in.”
Until now, many genetic studies in cardiovascular health have looked only at DNA sequence variants and did not consider the environmental factors that might interact with genes. Considering lifestyle factors in the context of a genetic analysis offers the possibility of identifying novel genes relevant to these complex risk factors and may provide clues to intervention points.
The investigators emphasize the possible impact such a large study ultimately could have on clinical practice.
“The potential of this study is great in terms of the clues it could provide about the underlying biological pathways that are involved, which may identify pharmacologic or behavioral points of intervention aimed at improving risk factor profiles,” said Ingrid B. Borecki, PhD, also a principal investigator, an associate professor of genetics and biostatistics and co-director of the Division of Statistical Genomics.
“These large-scale, collaborative epidemiologic studies represent a nontraditional mode of scientific cooperation that continues to provide greater insight into the genetic architecture of cardiovascular disease than we have been able to achieve in the past,” she said.
The study is timely, according to the researchers, since cardiovascular and heart disease remain a leading cause of death and disability in the United States and worldwide.
“Public health is driving our motivation to study this problem,” Borecki said. “We hope to gain insight that would allow us to develop models to identify people at elevated risk and to offer interventions or therapies most effective for them. Progress in this area could impact the management of health-care costs and, most importantly, we hope it will help people live healthier, more fulfilled lives.”
This work is supported by the National Institutes of Health (NIH) grant number R01 HL118305-01A1.
Washington University School of Medicine’s 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient-care institutions in the nation, currently ranked sixth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.