Paul Auer doesn’t have a scalpel or a stethoscope, but his work is having an impact on the treatment of heart disease.
Auer, an assistant professor of biostatistics in the University of Wisconsin-Milwaukee’s Joseph J. Zilber School of Public Health, uses mathematics and computers as his tools in the fight against heart disease, the leading cause of death in the United States.
He is part of a team that published research in the July 3 issue of the New England Journal of Medicine (NEJM) that showed strong evidence of links between four specific gene mutations and lower levels of triglycerides in the blood. Auer was one of the lead authors on the paper, which received national attention in the general media.
The work sheds light on the biological role of triglycerides and contributes to a growing body of knowledge that suggests that high triglyceride levels — rather than low levels of HDL cholesterol, another type of fat in the blood — are a major culprit in heart disease.
Fats circulating in the blood have long been associated with risk of coronary artery disease, the most common form of heart disease. These fats, or lipids, come in several forms, including low-density lipoproteins (LDL cholesterol), high-density lipoproteins (HDL) and triglycerides. Medical researchers have established links between these fats and the development of coronary artery disease, but many of the mechanisms remained unclear.
Auer and other researchers involved in these studies are combining their efforts to try to pinpoint specific genes that impact diseases.
“It’s significant in terms of public health research because heart attacks and heart disease are a leading cause of death,” says Auer of the recently published research. “Findings like these that could help prevent heart disease are very exciting.”
In this case, the researchers studied protein coding regions of 18,666 genes in 3,734 people to find four rare genetic mutations. They discovered four distinct mutations within one gene that are tied to lower blood triglycerides. Then Auer and the other statistical geneticists went to work to establish a relationship between the mutations and the incidence of heart disease, comparing heart disease rates in 498 people who had the mutations with more than 110,000 who did not. They found that the mutations not only lower triglycerides, but also reduce a person’s risk of coronary heart disease by 40 percent.
Since the mutations all cripple the same gene, called APOC3, this suggests a powerful strategy in developing new drugs against heart disease, say the study’s authors.
“The combination of our genetic results, together with recent clinical trials of drugs that raised HDL levels but failed to prevent heart disease, are turning decades of conventional wisdom on its head,” said senior author of the NEJM paper, Sekar Kathiresan. He is a Broad Institute associate member and director of preventive cardiology at Massachusetts General Hospital.
Auer was one of approximately 100 researchers involved in the study. “This type of project lasts many years and is the culmination of a lot of effort by many people at many institutions,” notes Auer.
“It’s good to reach the finish line with the publication of the research,” he says, “but there’s more work to be done.”
This type of statistical detective work is called Big Data Analytics, and is becoming an increasingly important part of health care as researchers comb through genetic information and large-scale, long-term compilations of medical records, like the Women’s Health Initiative, to establish links between genes and disease. The eventual goal is to develop more personalized medical care, based on individual genetic information.
The Zilber School of Public Health has developed a strong core of biostatisticians and other researchers working in this Big Data area for ways to improve treatments and minimize side effects of medications.
The ability to share Big Data quickly with high-capacity computing makes it possible for researchers around the country to work together in real time, Auer says. He started his work on this project, funded by the National Heart, Lung, and Blood Institute, at the Fred Hutchinson Cancer Research Center in Seattle. He was attracted to the Zilber School because he wanted to be part of a high-energy public health school startup. He also liked the School’s commitment to social and environmental justice. Part of his previous research has focused on genetic links to diseases that are more common among African Americans and Latinos.
Auer anticipates working on the follow-ups to this study. “There are many other studies that have similar goals in mind, looking at the genes linked to heart disease and even cancer. We’ll certainly be involved in many more experiments of this nature at UWM.”
