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Immune-Related, Psychiatric Disorders Share Genetic Ties, New Analysis Finds

NEW YORK — Psychiatric disorders are genetically correlated with a number of immune-related diseases, a new study has found.

Previous studies have hinted that certain immune disorders are linked to an increased risk of psychiatric disorders, and vice versa.

Through a series of genetic association studies and Mendelian randomization analyses, researchers from Yale University School of Medicine examined the directionality of the associations between psychiatric and immune-related traits and whether any other factors affected those associations. As they reported on Wednesday in JAMA Psychiatry, they found that genetic liability for psychiatric traits was associated with risk for immune-related trait through vertical pleiotropy, or when one phenotype has a direct effect on another.

"In this genetic association study, our comprehensive genetically informed inference analyses identified several robust associations of psychiatric phenotypes with immune-related phenotypes, but not vice versa, suggesting the predominant directional associations underlying large-scale epidemiological associations may be behavioral in origin," senior author Renato Polimanti from Yale and the Veteran Affairs Connecticut Healthcare System and colleagues wrote in their paper.

For their analysis, the researchers drew upon summary statistics from genome-wide association studies from the published literature, data repositories, and consortium datasets and focused on 14 psychiatric and 13 immune traits as well as 15 other risk factors. They uncovered 44 genetically linked psychiatric-immune phenotype pairs, including 31 positive correlations and 13 negative ones.

Most of the positive correlations involved immune-related phenotypes like asthma, Crohn's disease, ulcerative colitis, and hypothyroidism and psychiatric traits like depression, anxiety, major psychoses, and substance abuse disorders. Meanwhile, negative correlations were found between allergic rhinitis, primary sclerosing cholangitis, and type 1 diabetes and psychiatric traits. This suggested to the researchers that there may be different patterns of shared liability between these types of traits.

Through a series of bidirectional Mendelian randomization analyses, they homed in on about half a dozen associations that further survived multiple testing corrections. These included associations between attention deficit hyperactivity disorder (ADHD) and rheumatoid arthritis, hypothyroidism with major depressive disorder, and schizophrenia with Crohn's disease.

Some of these ties, the researchers noted, were influenced by other variables. For instance, the association between ADHD and rheumatoid arthritis was attenuated by eight other risk factors, such as body mass index and educational attainment.

The researchers additionally found an association between major depressive disorder and asthma, which is in line with previous work. They suggested that depression could influence how asthma symptoms are experienced to lead to increased diagnosis, or that depression could lead to chronic stress on helper T cells to contribute to the development of asthma.

This could indicate that the directional association between immune and psychiatric traits could be behavioral or due to other linked factors, they said.

They also examined what genetic loci were linked to the six associations they found through their Mendelian randomization analyses. Those with concordant psychiatric-immune associations were more likely to be expressed in brain tissue and were enriched in the transcriptomic profiles of fetal astrocytes and some cortical neurons. Both concordant and discordant loci were enriched in neurogenesis, neural differentiation, and GABAergic signaling.

"Taken together, biological characterizations of the loci comprising significant genetic correlations and [Mendelian randomization] outcomes converge to indicate stronger enrichment for brain- and behavior-related mechanisms in comparison with peripheral pathways," the researchers wrote.