Abstract
A recent publication reported an exciting polygenic effect of schizophrenia (SCZ) risk variants, identified by a large genome-wide association study (GWAS), on total brain and white matter volumes in schizophrenic patients and, even more prominently, in healthy subjects. The aim of the present work was to replicate and then potentially extend these findings. According to the original publication, polygenic risk scores—using single nucleotide polymorphism (SNP) information of SCZ GWAS—(polygenic SCZ risk scores; PSS) were calculated in 122 healthy subjects, enrolled in a structural magnetic resonance imaging (MRI) study. These scores were computed based on P-values and odds ratios available through the Psychiatric GWAS Consortium. In addition, polygenic white matter scores (PWM) were calculated, using the respective SNP subset in the original publication. None of the polygenic scores, either PSS or PWM, were found to be associated with total brain, white matter or gray matter volume in our replicate sample. Minor differences between the original and the present study that might have contributed to lack of reproducibility (but unlikely explain it fully), are number of subjects, ethnicity, age distribution, array technology, SNP imputation quality and MRI scanner type. In contrast to the original publication, our results do not reveal the slightest signal of association of the described sets of GWAS-identified SCZ risk variants with brain volumes in adults. Caution is indicated in interpreting studies building on polygenic risk scores without replication sample.
Highlights
The Psychiatric Genome-Wide Association Study (GWAS) Consortium has recently published a large GWAS, including 9394 schizophrenia (SCZ) cases and 12 462 healthy controls, identifying common variants that contribute to SCZ susceptibility with relatively small odds ratios.1 Besides these genome-wide significant loci, evidence has been accruing that a significant proportion of the risk for SCZ may lie in markers not achieving genome-wide significance in GWAS
A recent original publication7 reported an effect of GWASidentified SCZ risk variants, when compiled to polygenic scores, on total brain and white matter volumes in SCZ and even more pronounced in healthy individuals
SNPs belonging to PWM with the different brain volumetric variables
Summary
The Psychiatric Genome-Wide Association Study (GWAS) Consortium has recently published a large GWAS, including 9394 schizophrenia (SCZ) cases and 12 462 healthy controls, identifying common variants that contribute to SCZ susceptibility with relatively small odds ratios. Besides these genome-wide significant loci, evidence has been accruing that a significant proportion of the risk for SCZ may lie in markers not achieving genome-wide significance in GWAS. The Psychiatric Genome-Wide Association Study (GWAS) Consortium has recently published a large GWAS, including 9394 schizophrenia (SCZ) cases and 12 462 healthy controls, identifying common variants that contribute to SCZ susceptibility with relatively small odds ratios.. The Psychiatric Genome-Wide Association Study (GWAS) Consortium has recently published a large GWAS, including 9394 schizophrenia (SCZ) cases and 12 462 healthy controls, identifying common variants that contribute to SCZ susceptibility with relatively small odds ratios.1 Besides these genome-wide significant loci, evidence has been accruing that a significant proportion of the risk for SCZ may lie in markers not achieving genome-wide significance in GWAS. Was calculated based on the nominally associated alleles in a discovery sample This polygenic score explained up to 3% of variance in SCZ in a number of independent samples.. Some studies described associations for example, with cognitive aging or with a functional imaging substrate of working memory processing, others reported a lack of association with psychosis dimensions or intelligence.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.