Researchers Find 108 Genetic Links To Schizophrenia

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http://www.scienceofwonder.org/researchers-find-108-genetic-links-to-schizophrenia/

After analyzing DNA samples from over 150,00 people, researchers have found more than a hundred specific regions in the human genome associated with schizophrenia risk. The findings, published in Nature this week, support theories that immune system dysfunction is involved in the development of the disorder.

Drug research for schizophrenia has seen little innovation in the last 60 years. Current medications treat only psychosis, without addressing the cognitive symptoms. Part of that is because the biological mechanisms underlying schizophrenia aren’t well understood. 

So, to identify the genetic underpinnings of psychiatric traits, hundreds of researchers from the Schizophrenia Working Group of the Psychiatric Genomics Consortium performed a genome-wide association study, comparing genomes of 36,989 individuals diagnosed with schizophrenia to that of 113,075 controls. This is the largest genomic dragnet of any psychiatric disorder ever, according to the National Institutes of Health

After winnowing down from 9.5 million genomic areas, the team identified 128 independent genetic variants in 108 genetic locations (called loci) that contribute to disease susceptibility. Of these chromosomal sites, 83 are new and have never been linked to the disorder. 

Those 108 loci are where the DNA sequence in people with schizophrenia tends to be different from the sequence in people without it, Nature explains, and each contributes a small amount to the overall risk of developing the condition. Many of the variations seem to be common, so even though most people will have some of them, people with schizophrenia have more.

Within seven years, “our consortium has moved from identifying only a handful of loci associated with schizophrenia, to finding so many that we can see patterns among them,” Stephan Ripke of the Broad Institute says in a news release. “We can group them into identifiable pathways — which genes are known to work together to perform specific functions in the brain.”

Many of the newly implicated genes are involved in neurotransmission, including genes that are active in pathways essential to learning and memory, as well as communication between brain cells. There was also an association with variation in the gene that codes for a dopamine receptor, which is a target for current antipsychotic medications. Furthermore, the team also found a link to genes that are known to function in immune processes; the involvement of the immune system has long been speculated, though the significance of the connection still remains a mystery. 

“This really is now cementing most of the genetic data of the world in schizophrenia and putting it all together,” Michael O’Donovan of Cardiff University tells the Wall Street Journal. But they caution that there’s still much to learn about the genetics of schizophrenia. The new findings, he adds, likely account for just 3 percent to 4 percent of the total contribution of genetic and non-genetic factors in schizophrenia. Researchers are now working on pinpointing the specific sequences and genes that confer risk.

Source: Array

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