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Inflammatory biomarkers may influence schizophrenia risk

Mendelian randomization assumptions indicated C-reactive protein had a protective effect on risk for schizophrenia, while soluble interleukin-6 receptor increased risk.

“An association between schizophrenia and the immune system was suggested more than a century ago. Infections during pregnancy and early childhood, as well as autoimmune diseases, have been linked to an increased risk of schizophrenia. In addition, findings from the largest genome-wide association study of schizophrenia to date corroborate that immune dysregulation plays a role in the pathogenesis of schizophrenia,” Fernando Pires Hartwig, MSc, of Federal University of Pelotas, Brazil, and colleagues wrote.

To determine if inflammatory biomarkers affect risk for schizophrenia, researchers conducted a two-sample mendelian randomization study using genetic variants associated with inflammatory biomarkers as instrumental variables. Researchers used summary association results from large consortia of candidate gene or genome-wide association studies. Gene-inflammatory biomarker associations were estimated from pooled samples ranging from 1,645 to 80,000 individuals and gene-schizophrenia associations were estimated from approximately 30,000 patients and 45,000 ancestry-matched controls. Study participants tended to be of European ancestry and approximately 50% were male.

Using 18 C-reactive protein genetic instruments indicated a pooled odds ratio estimate of 0.9 (95% CI, 0.84-0.97) per twofold increment in C-reactive protein levels. Results using different mendelian randomization methods and more “conservative” instruments were consistent with this.

Soluble interleukin-6 receptor was associated with an odds ratio of 1.06 (95% CI, 1.01-1.12) per twofold increment.

Estimates for interleukin-1 receptor antagonist were inconsistent and pooled estimates were imprecise, according to researchers.

In an accompanying editorial, Enda M. Byrne, PhD, of the University of Queensland, Brisbane, Australia, and colleagues discussed the accuracy of two-sample mendelian randomization.

“While [mendelian randomization] will not be able to solve all questions of causality in psychiatry, it is a potentially powerful tool for the epidemiologist that has the potential to guide further research into possible causal risk factors. At the very least, it may help to reduce wasted research spending on [randomized controlled trials] that are unlikely to succeed,” they wrote. “We advocate that authors, reviewers, and editors help enforce the robustness of the field by only conducting and reporting [mendelian randomization] analyses in which SNP-exposure associations are genome-wide significant and that ensure that the genetic variants studied and their potential influences on outcomes are not associated with any confounders through pleiotropy.” – by Amanda Oldt

Disclosures: The authors report no relevant financial disclosures.