Uncommon genetic allele variants may play a vital role in treatment-resistant depression, finds study

By Hugo Francisco de SouzaAug 3 2023Reviewed by Lily Ramsey, LLM In a recent study published in the Scientific Reports Journal, researchers used next-generation exome-wide sequencing to identify any association between treatment-resistant depression and uncommon functional genetic alleles.

Exome-sequencing in mental health research Major depressive disorder is a serious mental health condition characterized by persistently depressed mood or loss of interest in activities, causing significant impairment in daily life. The discordance between observed heritability in MDD diagnosis versus the apparent lack thereof in antidepressant response suggests the role of uncommon genetic variants not typically captured during GWAS analyses.

The TRD cohort comprised 150 individuals from the National Institute of Mental Health , 24 individuals being treated at the University of Michigan, and eight from the Sequenced Treatment Alternatives to Relieve Depression study for a total of 182 patients. Gene-level analyses involved first classifying gene variants into three nested sets – Uncommon, functional, and non-harmful ; uncommon, functional, and damaging ; and uncommon, functional, and with nonsense mutations . Variants were categorized and processed by the gene.

Researchers identified and tested 14,083 genes at the gene level to investigate their association with TRD. More than fifty genes were found to have excess variants associated with TRD, with the top five being ZNF248, PYHIN1, PRKRA, SLC7A8, and STK19.

Source: Healthcare Press (healthcarepress.net)

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