Gene variants linked to higher schizophrenia risk

WASHINGTON — A handful of typos in a mysterious region of the human genetic code are connected to a slightly higher risk of schizophrenia, new studies show.

In a first-of-its-kind look at the genetic elements of schizophrenia, a massive international effort focused on seven spots of genetic variation. Dozens of scientists then published three papers from the effort on Thursday in the journal Nature. Those genetic blips account for at most one-third of genetically caused schizophrenia.

Based on studies of identical twins, scientists figure that about half of schizophrenia is inherited with the rest having other causes.

What the studies show more than anything is that schizophrenia doesn’t have a single genetic cause. It is more like a massive jigsaw puzzle and researchers just found a few end pieces, said Dr. Thomas Insel, director of the National Institute of Mental Health, which financed much of the work.

Researchers looked at the genomes of more than 50,000 people, some with schizophrenia and some without. Schizophrenia, first described 100 years ago as a split between thought and perception, includes thinking disorders, hallucinations, psychosis and odd behaviors, Insel said.

The findings have little practical immediate benefit, but “give us a little bit of insight into the biology of the disease,” said one of the lead authors, Dr. Kari Stefansson, chief executive officer of deCODE Genetics in Iceland.

The risk increases found in the papers are small — a jump of between 15 and 25 percent above the normal 1 in 100 risk of developing schizophrenia. And all but one of the genetic variations are common to most of the population, so they can’t be used much as a screening tool either.

What’s intriguing is where five of those seven genetic variations lie.

Five are on “the short arm” of a single chromosome connected with all sorts of diseases, including ones relating to immune illnesses, such as Type 1 diabetes, said Insel, who was not part of the study teams. He calls that area “the Bermuda Triangle of the human genome.”

Past studies have found an association between schizophrenia and babies born in winter and spring, hypothesizing that an immune system reaction to viral infection during pregnancy may be a factor. The location of five variants in that immune disorder-correlated region, is “provocative,” said another study lead author Dr. Pablo Gejman, director of the Center for Psychiatric Genetics at NorthShore University Health Systems in Evanston, Ill.

Stefansson cautioned about seeing too much of a connection with immune disorders: “It’s guilt by association; it’s not really a link.”

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