Large-scale genetic study identifies 14 genes linked to neuroticism

Neuroticism is a key personality trait described by well-established psychological theories, associated with a tendency towards emotional instability and negative emotions. Past studies found that this personality trait often goes hand in hand with various mental health disorders, as well as some chronic and severe medical conditions.

Technological advances have opened new possibilities for the study of genetic factors contributing to diseases and psychiatric disorders. Similar methods could also help to shed light on genes that increase the probability of a person exhibiting specific personality traits, including neuroticism.

Past research has unveiled over 100 locations on the human genome that are associated with neuroticism. Nonetheless, much about this personality trait’s inheritability remains to be discovered.

Researchers at Fudan University in China recently set out to further investigate the genetic underpinnings of neuroticism, by analyzing data from the UK Biobank, a large database containing genetic and health-related information collected from thousands of people in the UK. Their paper, published in Nature Human Behavior, pin-points 14 genes that were linked to neuroticism in the data they analyzed, 12 of which had not been identified before.

“Existing genetic studies of neuroticism have been largely limited to common variants,” Xin-Rui Wu, Ze-Yu Li and their colleagues wrote in their paper. “We performed a large-scale exome analysis of white British individuals from UK Biobank, revealing the role of coding variants in neuroticism. For rare variants, the collapsing analysis uncovered 14 neuroticism-associated genes.

“Among these, 12 (PTPRE, BCL10, TRIM32, ANKRD12, ADGRB2, MON2, HIF1A, ITGB2, STK39, CAPNS2, OGFOD1 and KDM4B) were novel, and the remaining (MADD and TRPC4AP) showed convergent evidence with common variants.”

The UK BioBank offers a large pool of data that researchers worldwide can analyze to explore the interactions between different genes, lifestyle choices and health disorders. As part of their recent study, Wu, Li and their colleagues analyzed 454,787 exome sequencing data from the UK BioBank, to identify genes linked to neuroticism. Their analyses brought to light 12 new genes associated with this personality trait while confirming the association to neuroticism of 2 genes already uncovered in previous studies.

“The heritability of rare coding variants was estimated to be up to 7.3% for neuroticism,” wrote Wu, Li and their colleagues.

“For common variants, we identified 78 significant associations, implicating 6 unreported genes. We subsequently replicated these variants using meta-analysis across four other ancestries from UK Biobank and summary data from the 23andMe sample. Furthermore, these variants had widespread impacts on neuropsychiatric disorders, cognitive abilities and brain structure.”

The recent findings gathered by Wu, Li and his colleagues contribute to the present understanding of neuroticism and its genetic underpinnings. In the future, they could inspire new genetic studies focusing on neuroticism or other personality traits. Eventually, these research efforts could inform the development of diagnostic and therapeutic tools for neuropsychiatric disorders linked with specific personality traits.

“Our findings deepen the understanding of neuroticism’s genetic architecture and provide potential targets for future mechanistic research,” wrote Wu, Li and their colleagues.

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