His research focuses on the genetic basis of metabolic disorders that contribute common diseases such as heart disease and fatty liver disease. Together with his scientific partner, Dr. Helen Hobbs, he has identified genes that play major roles in the metabolism of fats, cholesterol, and triglycerides, and elucidated the biological roles of their protein products. His laboratory showed that loss-of-function mutations in PCSK9 are associated with low plasma levels of cholesterol and confer protection from coronary heart disease. In addition, the Hobbs-Cohen laboratory identified the first genetic cause of nonalcoholic fatty liver disease in humans.