Figuring out what genes are involved in causing a disease and what turns those genes on or off have been the toughest problems in genetics. Now, researchers at the Johns Hopkins University School of Medicine and the Karolinska Institute in Sweden have released a pathbreaking report on a way to evaluate one gene-regulation system. It was an investigation of epigenetics, a popular area of molecular biology. Epigenetics looks for modifications of genes that can help determine disease risk. The paper was published in Nature Biotechnology.
Patients with rheumatoid arthritis were chosen as the study’s subjects. Rheumatoid arthritis is a crippling autoimmune disease that affects 1.5 million Americans. The new study involved 354 newly diagnosed rheumatoid arthritis patients and 337 healthy people who served as controls. Dr. Bradley Bernstein of Harvard said, “This is one of the first studies that looks for an epigenetic disease association in a really rigorous fashion.” Dr. Bernstein was not associated with the study.
Researchers compared both groups’ white blood cells, examining their DNA. The researchers focused their attention on the chemical tags that tell genes to be active or not. The goal was to review the chemical tags, called methyl groups, that could adhere to the genes and turn them on or off.
Out of hundreds of chemical tags, only four seemed truly related to the disease. Dr. Andrew Feinberg of Johns Hopkins, a lead author of the study, said that those four were in a cluster of genes that controls the immune response and that was known to affect the risk of rheumatoid arthritis. There were control group subjects who had gene variations associated with arthritis risk, but they did not have those four chemical tags and did not have the disease.
The chemical tags that turn the genes on and off are not reliable, making the study much more complicated. Their presence can be affected by the environment or medications, be a consequence of a disease or be responsible for setting off a condition, or even be a result of the activity of other, distant genes. Dr. Bernstein said, “That’s the problem, the arrow of time problem. What is cause and what is effect?”
Kun Zhang of the University of California, San Diego, said, “I am quite impressed with their level of rigor and sophistication.” He continued on to say that in previous genomic studies, researchers with papers in leading journals “have made major claims, but after a few months or a year they were retracted.” He says that he believes that those investigators “did not treat their data very carefully.”