Schizophrenia genetics come into focus

By Eleanor McDermid, Senior medwireNews Reporter

A study in Nature Genetics illustrates the large impact of genetic variation on risk for schizophrenia.

In line with current thinking, the researchers found that the genetic architecture of schizophrenia is characterized by large numbers of single-nucleotide polymorphisms (SNPs) with relatively small individual effects.

Indeed, extrapolating from their analysis, they estimate that between 6300 and 10,200 independent but largely common SNPs contribute to schizophrenia.

“As one gene or structural element could contain multiple independent associations, the number of genes ultimately determined to harbor causal variation for schizophrenia will be smaller, and we expect that these genes will implicate one or more biological pathways fundamental to disease risk,” they write.

Furthermore, the team calculates that these loci account for around half of a person’s liability to develop schizophrenia.

Patrick Sullivan (University of North Carolina, Chapel Hill, USA) and team draw their conclusions from data for one discovery cohort and two replication cohorts, which together comprised more than 21,000 schizophrenia patients and 38,000 controls.

They identified 22 genetic loci that significantly associated with schizophrenia. Of these, five were already known to be associated with schizophrenia, one with bipolar disorder, and three with psychiatric disease overall, leaving 13 newly identified loci.

Of note, the findings suggest a role for calcium signaling in schizophrenia, and confirm the strong associations with the major histocompatibility complex and with MIR137. Also, 13 of the 22 regions contain long intergenic noncoding RNAs, which the researchers say is consistent with the identified loci mainly affecting gene transcription rather than actually altering protein sequences.

“These results provide deeper insight into the genetic architecture of schizophrenia than ever before achieved,” comment Sullivan et al.

They say: “We propose a goal for the field: the identification of the top 2,000 loci (for example) might be sufficient to confidently and clearly identify the biological processes that mediate risk and protection for schizophrenia.”

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