Do similar polygenic risk factors for schizophrenia apply across ethnic groups?

Polygenic risk factors for schizophrenia and bipolar disorder-- and the genetic factors that distinguish between them – which have been derived from populations of European descent  contribute to schizophrenia risk in Japanese people, new research suggests.1 

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.

Our correspondent’s highlights from the symposium are meant as a fair representation of the scientific content presented. The views and opinions expressed on this page do not necessarily reflect those of Lundbeck.

References

1. Ohi K et al. Int J Neuropsychopharmacol 2020;23(3):157-164

2. Ruderfer M et al. Cell. 2018 Jun 14; 173(7): 1705–1715.e16

3. Schizophrenia Working Group of the Psychiatric Genomics Consortium. Nature 2014;511:421–427

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