Most of our understanding about genetic risk relating to schizophrenia and other major psychiatric disorders derives from genome-wide association (GWAS) studies in people of European origin.
This applies both to the variants that apply to specific conditions, such as bipolar disorder (BD) and schizophrenia and those that are implicated in both diagnostic groups.
The BD and Schizophrenia Working Group of the Psychiatric Genomics Consortium recently identified 114 genome-wide loci implicating synaptic and neuronal pathways which the two disorders shared and other variants thought to contribute to differences in biology between the disorders.2
Both bipolar disorder and schizophrenia are thought to be 60-80% heritable, and they share some genetic risk factors2
Would findings in Japan match those from people of European descent?
So, there is great interest in seeing whether the same or similar factors emerged from a study in Japan, which included both people with BD and schizophrenia and their first degree relatives unaffected by disease, but presumed to be at high risk.1
Kazutaka Ohi (Gifu Graduate School of Medicine) and colleagues used large European GWAS datasets as discovery samples to derive polygenic risk scores.
They then applied these scores to 335 Japanese target subjects (131 people with schizophrenia, 57 unaffected first degree relatives and 147 healthy controls) and investigated their effect on risk in Japanese patients with schizophrenia and unaffected first-degree relatives.
Genetic risk scores derived in Europe are relevant in Japan
Polygenic risk scores
The polygenic risk scores obtained from European patients with schizophrenia were also significantly higher in Japanese patients than in Japanese healthy controls.
Interestingly, the risk scores related to BD in Europe were also nominally higher in Japanese patients with schizophrenia than in healthy controls.
And the risk scores differentiating schizophrenia patients from those with BD in Europe were marginally higher in Japanese schizophrenia patients than healthy controls.
The authors of the Japanese study conclude that polygenic factors related to European schizophrenia and BD and the polygenic components differentiating schizophrenia from BD contribute transethnically to schizophrenia risk in Japanese people.
The major GWAS study published in 2014 by the Psychiatric Genomics Consortium, sequenced more than 37,000 patients and 113,000 controls and found 108 schizophrenia-associated genetic loci.3
Adding together the increased risk associated with all single nucleotide polymorphisms (SNPs) identified as significant accounted for around 30% of the estimated genetic vulnerability to schizophrenia. There was considerable overlap between these SNPs and those thought to be important in bipolar disorder.