Genetic evidence for causal effects of immune dysfunction in psychiatric disorders: where are we?

• Published in: Translational psychiatry Vol. 14; no. 1; pp. 63 - 11
• Main Authors: Iakunchykova, Olena, Leonardsen, Esten H., Wang, Yunpeng
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 26.01.2024; Nature Publishing Group
• Subjects: 45; 45/43; 631/208/212; 692/699/476; Antigens; Behavioral Sciences; Biological Psychology; Causality; Chronic illnesses; Cytokines; Disease; Expert Review; Genome-Wide Association Study; Humans; Hypotheses; Immune system; Infections; Medicine; Medicine & Public Health; Mendelian Randomization Analysis; Mental disorders; Mental Disorders - genetics; Models, Statistical; Neurosciences; Pharmacotherapy; Psychiatry
• ISSN: 2158-3188; 2158-3188
• DOI: 10.1038/s41398-024-02778-2

The question of whether immune dysfunction contributes to risk of psychiatric disorders has long been a subject of interest. To assert this hypothesis a plethora of correlative evidence has been accumulated from the past decades; however, a variety of technical and practical obstacles impeded on a cause-effect interpretation of these data. With the advent of large-scale omics technology and advanced statistical models, particularly Mendelian randomization, new studies testing this old hypothesis are accruing. Here we synthesize these new findings from genomics and genetic causal inference studies on the role of immune dysfunction in major psychiatric disorders and reconcile these new data with pre-omics findings. By reconciling these evidences, we aim to identify key gaps and propose directions for future studies in the field.