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The 'Maze' of Schizophrenia Genes

A genome-wide association study including some 38,000 cases and 113,000 controls has linked 108 loci to schizophrenia, the authors report in Nature today.

Of those loci, the Schizophrenia Working Group of the Psychiatric Genomics Consortium led by Cardiff University's Michael O'Donovan notes that 83 loci had not been previously linked to the disease.

"In the past, people thought schizophrenia must happen because of some really bad mutations in a person not seen in people around them," co-author Steve McCarroll from the Broad Institute tells LiveScience. "This study shows a substantial part of the risk of schizophrenia comes from many tiny nudges to the genome that all humans share."

Among the loci the team linked to schizophrenia in this study are ones within DRD2, which is a target of many antipsychotic drugs; GRM3, GRIN2A, SRR, and GRIA1 which are involved in glutamatergic neurotransmission and synaptic plasticity; and in CACNA1C, CACNB2, and CACNA1I, which encode subunits of voltage-gated calcium channels.

By mapping the 108 loci to areas of active enhancers in more than 50 cell and tissue lines, the researchers found that schizophrenia-linked genes were more likely to be active in the brain than in, say, bone or fibroblasts.

The associations, though, were also enriched at sites with immune function, especially B-lymphocyte lineages, the researchers say. This finding, LiveScience notes, may support the notion that immune response or mis-response has a role in disease etiology.

"It's a map or maze. It's telling you were to start, it's not telling you where to end," O'Donovan tells the Associated Press.