Cohen to discuss link between population genetics and chronic disease

By Cathy Frisinger

Cohen to discuss link between population genetics and chronic disease
Dr. Jonathan Cohen

Chronic conditions like heart disease, liver disease, and obesity are among the leading causes of death around the world. While lifestyle choices such as smoking and diet play critical roles in the development of these conditions, genetic factors also play a significant part and, in many instances, genetic underpinnings of disease and lifestyle factors intersect in crucial ways.

Dr. Jonathan Cohen has devoted his career at UT Southwestern Medical Center to teasing out the genetic components of these diseases by examining genetics in a cohort, investigating the underlying biological relationships that contribute to disease among a large population. He will deliver a presentation about his work titled “Simple Genetics for Complex Diseases” as the first 2017 talk in the President’s Lecture Series, which is entering its 12th year. The Jan. 26 lecture will take place at 4 p.m. in the Tom and Lula Gooch Auditorium.

“Genetic information on its own can only go so far in furthering understanding. The key to making use of that knowledge is to be able to match genotype information with phenotype information, or actual physical characteristics,” said Dr. Cohen, Professor of Internal Medicine. “Using both genotype and phenotype data from the Dallas Heart Study, a multi-ethnic population-based study comprising some 3,500 individuals, we were able to gain insights into important metabolic conditions that contribute to lipid disorders and heart disease.”

Further, Dr. Cohen, together with his scientific partner, Dr. Helen Hobbs, pioneered a new way of looking at genetic foundations of complex chronic diseases such as coronary artery disease, focusing on rare mutations rather than common alleles. This approach yielded insights when they were studying lipid metabolism and identified a woman who had two genetic mutations that, together, caused her to have a near absence of a protein called PCSK9 that blocks cholesterol removal from the body. This woman was in good health, which meant that drugs targeting PCSK9 could be developed to treat high cholesterol. Two such drugs were approved by the Food and Drug Administration in 2015 and are an effective treatment for individuals who have familial hypercholesterolemia that is not sufficiently lowered by statins.

Another key focus for Dr. Cohen has been nonalcoholic fatty liver disease, which has become a common condition as the obesity epidemic has grown. The lab’s work revealed two gene variants that are associated with liver inflammation, cirrhosis, and liver cancer.

“This was exciting because it suggested that liver fat was not as benign as people had thought, but led to these diseases,” Dr. Cohen said. “By comparing genetic details and phenotypes of a specific population cohort, we were able to show that the growing epidemic of fatty liver disease will have serious public health consequences.”

His research has also provided insights into the control of fat and glucose uptake by adipose tissue. His laboratory identified a gene that plays a key role in the metabolic transition from fasting to feeding. These genes also affect the levels of cholesterol and triglycerides in the blood, and drugs to block their activity are currently in clinical trials.

Dr. Cohen grew up in South Africa and earned his Ph.D. in physiology at the University of Cape Town. He came to UT Southwestern in 1989 as a postdoctoral fellow working first with Dr. Scott Grundy, Professor of Internal Medicine, in the Center for Human Nutrition, and then with Dr. Hobbs, Professor of Internal Medicine and Molecular Genetics, in the Department of Molecular Genetics, during which time their lasting partnership was forged.

In 2015, Dr. Cohen was recognized with the Barbara Bowman Distinguished Texas Geneticist Award, and in 2016, he and Dr. Hobbs received the Passano Award, given for exemplary research that leads to real-world applications.

Dr. Cohen holds the C. Vincent Prothro Distinguished Chair in Human Nutrition Research.

Dr. Hobbs holds the Eugene McDermott Distinguished Chair for the Study of Human Growth and Development; the Philip O’Bryan Montgomery, Jr., M.D. Distinguished Chair in Developmental Biology; and the Dallas Heart Ball Chair in Cardiology Research.