New genetic links to psoriasis uncovered

In the first comprehensive study of the genetic basis of psoriasis, School of Medicine researchers have discovered seven new sites of common DNA variation that increase the risk of the troublesome skin condition. They also found that variations in one genetic region link psoriasis and a related joint disorder — psoriatic arthritis — to four autoimmune diseases: type 1 diabetes, Graves’ disease, celiac disease and rheumatoid arthritis.

The study’s results appeared April 4 in PLoS Genetics.

“Our research shows that small but common DNA differences are important in the development of psoriasis,” said lead investigator Anne Bowcock, Ph.D., professor of genetics. “Although each variation makes only a small contribution to the disease, patients usually have a number of different genetic variations that increases their risk of psoriasis and psoriatic arthritis.”

The DNA variations uncovered by the researchers point to different biological pathways that underlie psoriasis and may eventually lead to targeted drugs and treatments, Bowcock said.

An estimated 7 million Americans have psoriasis, an autoimmune disease that occurs when the body’s immune cells mistakenly attack the skin. The condition is characterized by red, scaly patches that can be itchy, painful or both. Some 10 percent to 30 percent of patients with psoriasis develop painful and debilitating psoriatic arthritis.

The researchers focused on points of common variation in the genome called single nucleotide polymorphisms, or SNPs. While most of the 3 billion nucleotides that constitute DNA are thought to be identical in humans, some 10 million SNPs build variation into the genome and make each individual unique. Some of these SNPs play a crucial role in a person’s predisposition to disease or good health.

The investigators scanned more than 300,000 SNPs in the genomes of 223 psoriasis patients, including 91 who had psoriatic arthritis. They compared the DNA variations in people with psoriasis to those found in healthy control patients, looking for specific differences that may be linked to the disease. They then replicated their findings in a larger set of patients and healthy controls.

Bowcock and her team found seven novel DNA variations linked to psoriasis. The researchers found the strongest genetic risk for psoriasis lies in a region of the genome that contains the major histocompatibility complex (MHC), a collection of genes involved in distinguishing the body’s own cells from foreign invaders.

“Although this region has been known to play a major role in psoriasis, DNA variations in the MHC alone have been known to not be enough to trigger disease,” Bowcock said. “Only 10 percent of patients with variations in the MHC developed psoriasis. This tells us that other genetic or environmental factors also contribute to the disease.”

Notably, DNA variations on chromosome 4 were strongly linked to psoriatic arthritis. These same variations were also associated with psoriasis and had been previously linked to type 1 diabetes; rheumatoid arthritis; Graves’ disease, caused by an overproductive thyroid gland; and celiac disease, caused by the inability to digest gluten.

“Doctors have noticed that some psoriasis patients have these autoimmune diseases,” Bowcock said. “But we didn’t know whether this was a coincidence. Now we know there is a genetic component underlying all of these diseases.”