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Psychiatric Disease Blood Markers Proposed From Biochemical, GWAS Profiles

NEW YORK – Using blood biochemical profiles and data from psychiatric genome-wide association studies, Australian investigators have narrowed in on proposed blood-based biomarkers for psychiatric conditions, including markers found at higher- or lower-than-usual levels in individuals with different psychiatric conditions.

"Collectively, these data suggest that there are shared pathways that influence both biochemical traits and psychiatric illness," Murray Cairns, a researcher affiliated with the University of Newcastle and the Hunter Medical Research Institute's Centre for Brain and Mental Health Research, and his colleagues wrote in a paper describing the work published in Science Advances on Wednesday.

In the study, the researchers used linkage disequilibrium score regression (LDSR) analyses to search for potential ties between blood biomarkers reported in some 300,000 UK Biobank project participants and variants implicated in psychiatric conditions through 10 prior GWAS. Across the full set of biochemical profiles and conditions assessed, they saw significant associations with one or more psychiatric conditions for around 61 percent of the blood biochemical markers considered.

"Our data demonstrated that there is clear evidence of genetic overlap between blood-based measures and psychiatric phenotypes, as quantified by LDSR, which may indicate shared variants and pathways that predispose to these traits," the authors wrote. "It should be noted that the pleiotropic effect of variants on other traits could mediate these relationships, while some of these trait pairings were further shown in this study to be consistent with evidence of causality rather than just correlation."

Based on more than two dozen biomarkers in a polygenic score gleaned with genetic proxy data from the UK Biobank project, the team saw an association with a schizophrenia subtype marked by severe cognitive deficits in a group of almost 400 individuals from the Australian Schizophrenia Research Bank.

The team found that enhanced glucose levels in the blood corresponded with a rise in attention-deficit/hyperactivity disorder (ADHD) risk. On the other hand, increased blood levels of a chronic inflammation-linked C-reactive protein (CRP) marker appeared to coincide with increased risk of conditions such as major depressive disorder, post-traumatic stress disorder, and ADHD, for example, but was associated with reduced risk of obsessive-compulsive disorder, anorexia nervosa, schizophrenia, and other conditions.

With the help of a latent causal variable model, meanwhile, the investigators saw hints that the CRP, glucose, and other circulating biochemical biomarkers may have at least partially causal ties to some of the conditions considered rather than blood-based correlations with psychiatric disorders alone.

In other cases, the relationships were conditioned on additional traits or factors. When it came to schizophrenia, for example, the team found that bumped up blood levels of CRP were linked to reduced disease risk, though this effect hinged on additional contributors such as body mass index and interleukin-6 signaling.

"We found that the majority of biochemical traits tested were genetically correlated with at least one psychiatric trait, with evidence of convergent and divergent correlation profiles among the different disorders," the authors reported, adding that the evidence suggests that "there may be a causal relationship on psychiatric phenotypes through circulating C-reactive protein, glucose, and urate, which may have direct implications for clinical practice."

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