Schizophrenia is one of the most common serious mental health conditions, with a 1% global lifetime risk. By gathering data from a non-European population, a study published in Nature Genetics has discovered that there are differences in genetic associations with schizophrenia that differ across ancestries.

Although the exact causes of schizophrenia are unknown, it is thought to be a combination of environmental and genetic factors that contribute to an individual’s susceptibility. To determine which genes could confer a risk, scientists compared the genomes of those affected and unaffected to look for differences. These differences are then collated into a Polygenic Risk Score (PRS) for the disease.

PRS predictions are used to analyse multiple genes and variations and assign each variant a weight. The more risk-causing variants an individual has, the greater their risk. This differs from a single mutation leading to an increased risk, such as BRCA1 and BRCA2 – which confer a risk of 45% -60% for breast cancer. These studies require large datasets from multiple genomes to create a comprehensive picture. Where these genomes originate from can lead to unintentional bias.

The researchers found that most large-scale psychiatric studies have used sample genomes from European ancestry. By analysing 145 recently found genetic loci and applying these to an East Asian population of 58,140 – 22,778 of which were schizophrenia cases – the loci were only 45% as accurate in predicting the disease. By analysing this new population, 21 new associations were also found that were previously overlooked.

Highlighting the issues of using single ancestry populations for finding clinically relevant variants, the study concludes that using polygenic risk scores modelled on one population has reduced our ability to predict the disease in other populations. To remedy this, genome-wide association studies must gather larger and more varied samples from global populations. The exact causes of schizophrenia will be only be found with a world-wide approach to genome gathering and collaboration.

For further information on polygenic risk scores check out this video from SciShow

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