Polygenic analysis suggests the involvement of calcium signaling in executive function in schizophrenia patients

Kirchner, Sophie K.; Ozkan, Selen; Musil, Richard; Spellmann, Ilja; Kannayian, Nirmal; Falkai, Peter; Rossner, Moritz und Papiol, Sergi (2020): Polygenic analysis suggests the involvement of calcium signaling in executive function in schizophrenia patients. In: European Archives of Psychiatry and Clinical Neuroscience, Bd. 270, Nr. 4: S. 425-431

Abstract

Cognitive deficits are increasingly recognized as a core dimension rather than a consequence of schizophrenia (SCZ). The previous evidence supports the hypothesis of shared genetic factors between SCZ and cognitive ability. The objective of this study was to test whether and to what extent the variation of disease-relevant neurocognitive function in a sample of SCZ patients from the previous clinical interventional studies can be explained by SCZ polygenic risk scores (PRSs) or by hypothesis-driven and biomedical PRSs. The previous studies have described associations of the SNAP25 gene with cognition in SCZ. Likewise, the enrichment of several calcium signaling-related gene sets has been reported by genome-wide association studies (GWAS) in SCZ. Hypothesis-driven PRSs were calculated on the basis of the SNAP-25 interactome and also for genes regulated by phorbol myristate acetate (PMA), an activator of the signal transduction of protein kinase C (PKC) enzymes. In a cohort of 127 SCZ patients who had completed a comprehensive neurocognitive test battery as part of the previous antipsychotic intervention studies, we investigated the association between neurocognitive dimensions and PRSs. The PRS for SCZ and SNAP-25-associated genes could not explain the variance of neurocognition in this cohort. At a p value threshold of 0.05, the PRS for PMA was able to explain 2% of the variance in executive function (p = 0.05, uncorrected). The correlation between the PRS for PMA-regulated genes and cognition can give hints for further patient-derived cellular assays. In conclusion, incorporating biological information into PRSs and other en masse genetic analyses may help to close the gap between genetic vulnerability and the biological processes underlying neuropsychiatric diseases such as SCZ.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0940-1334
• Sprache: Englisch