Mass of gene clues point to inherited risk for schizophrenia


Three teams of scientists said on Wednesday they had identified hundreds of tiny genetic variants that together account for more than a third of the inherited risk for schizophrenia.

The flaws were netted in a trawl through the DNA of thousands of individuals, in the biggest study yet into the genetic origins of this enigmatic but crippling disease.

Schizophrenia is characterised by hallucinations and delusions, striking around one percent of the population. The disorder emerges in late adolescence or in early adulthood and can have a catastrophic effect.

The mechanisms of schizophrenia remain elusive, but heritability is known to be a big factor, accounting for between 70 and 90 percent of cases according to past research.

A small but important step was made last year in unveiling a first basket of genes that could be to blame.

Yet they account for only a few percent of cases, an achievement dwarfed by the new studies.

"Individually, these common variants' effects do not all rise to statistical significance," said Harvard University investigator Shaun Purcell, who co-led one of the three teams.

"But cumulatively, they play a major role, accounting for at least one-third -- and probably much more -- of disease risk."

The trio of papers points a finger especially at baulky genes on Chromosome 6.

This is in a gene-packed area called the Major Histocompatibility Complex, which plays a role in the immune system and in determining how and when other genes are switched on and off.

"This hotspot of association might help to explain how environmental factors affect risk for schizophrenia," the US National Institute of Mental Health (NIMH), which part-funded all three probes, said in a press statement.

"For example, there are hints of auto-immune involvement in schizophrenia, such as evidence that offspring of mothers with influenza while pregnant have a higher risk of developing the illness."

Some of the work also suggests similar genetic machinery may be responsible for schizophrenia and manic depression, also called bipolar disorder.

That finding is intriguingly at odds with the conventional medical diagnosis that determines the two conditions are quite distinct.

The studies, published in the British journal Nature, involved comparing more than 8,000 cases of schizophrenia and 19,000 otherwise healthy individuals, looking for telltale single variations in the genetic code.

The three research teams were the International Schizophrenia Consortium, the Molecular Genetics of Schizophrenia consortium and SGENE. In an exceptional move, all three teams shared their data in order to get the widest and deepest view.

Finding genetic clues could open the way, eventually, to a diagnostic test to help those at risk from the disease. It also opens up potential avenues for pharmaceutical engineers eyeing drugs to block malfunctioning genes.

ri/rl

Health-schizophrenia

AFP 011700 GMT 07 09


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