Two huge international studies show that people who lack certain chunks of DNA run a dramatically higher risk of getting schizophrenia, a finding that could help open new doors to understanding and diagnosing the disease.
These deletions are rare, each found in less than 1 percent of schizophrenia patients. But each one boosts the risk of disease by as much as 15-fold, by one estimate.
Scientists said studying such abnormalities may help them find new medications by shedding light on what causes the disease. And if enough rare aberrations can be found eventually, they may be combined into a test to help in diagnosis, said Kari Stefansson, chief executive officer of deCode Genetics of Reykjavik, Iceland, and an author of one of the studies.
Schizophrenia is currently diagnosed by its symptoms.
The human DNA can be thought of as a very long string of letters — about 3 billion of them — that sometimes form words (genes). Each newly identified deletion removes a section of about half a million to 2 million letters.
In the past, scientists have found specific genes and deletions linked to schizophrenia risk. But the new work is notable because two large studies independently identified the same two DNA deletions, and those aberrations have such a big impact on disease risk. Stefansson's paper also reports evidence for a third deletion.
While the DNA deletions are linked to only a tiny fraction of schizophrenia cases, it's not unusual that a very rare cause of a disease provides insights that apply more generally, said Dr. Pamela Sklar of Massachusetts General Hospital, an author of the other paper. She said such knowledge can lead to treatments for many people.
Both papers were published online Wednesday by the journal Nature. Experts not connected with the work praised the results.
"This is tremendous" for basic research into the disease, said Dr. Linda Brzustowicz of Rutgers University. But since the deletions found so far are related to such a small fraction of schizophrenia cases, she said it's too early for companies to offer to test people for them.
Stefansson's paper, which included authors from more than a dozen centers in the United States, Europe and China, reported findings from DNA tests in about 4,700 people with schizophrenia and more than 40,000 healthy people. Sklar's paper, which included scientists from 11 institutes in the United States, Europe and Australia, tested about 3,400 people with schizophrenia and 3,200 others.
Both papers found that while the deletions were rare in schizophrenia patients, they were even rarer in people without the disease. Scientists say the disease results from a combination of genetic predisposition and environmental influences.
The two deletions found by both research groups boost schizophrenia risk 12-fold and 15-fold, Stefansson's group calculated. A third deletion his group found appears to raise risk about threefold.
Sklar said she was "absolutely delighted" that the papers found the two deletions independently, using different methods.
Anne Pulver, a schizophrenia genetics expert at Johns Hopkins University, said the papers represent a welcome shift in focus for finding genetic variants that affect risk of schizophrenia.
Traditionally, that search has centered on relatively common variants, each with little effect on an individual's risk. The new approach seeks rare variants that play a larger role. The new approach should help identify subgroups of patients with different genetic causes for their disease, she said. Eventually that could lead to treatments that are tailored to the differing biological causes, with improved outcomes, she said.