Polygenic risk for schizophrenia and associated brain structural changes: A systematic review

C van der Merwe; R Passchier; M Mufford; R Ramesar; S Dalvie; D J Stein

doi:10.1016/j.comppsych.2018.11.014

Polygenic risk for schizophrenia and associated brain structural changes: A systematic review

Compr Psychiatry. 2019 Jan:88:77-82. doi: 10.1016/j.comppsych.2018.11.014. Epub 2018 Nov 29.

Authors

C van der Merwe¹, R Passchier², M Mufford³, R Ramesar⁴, S Dalvie⁵, D J Stein⁶

Affiliations

¹ UCT/MRC Research Unit for Genomic and Precision Medicine, Division of Human Genetics, Department of Pathology, Institute of Infectious Diseases and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa. Electronic address: celia.vandermerwe@uct.ac.za.
² Department of Psychiatry and MRC Unit on Risk & Resilience, University of Cape Town, Cape Town, South Africa.
³ UCT/MRC Research Unit for Genomic and Precision Medicine, Division of Human Genetics, Department of Pathology, Institute of Infectious Diseases and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
⁴ UCT/MRC Research Unit for Genomic and Precision Medicine, Division of Human Genetics, Department of Pathology, Institute of Infectious Diseases and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa; Department of Psychiatry and MRC Unit on Risk & Resilience, University of Cape Town, Cape Town, South Africa; Groote Schuur Hospital, Cape Town, South Africa.
⁵ UCT/MRC Research Unit for Genomic and Precision Medicine, Division of Human Genetics, Department of Pathology, Institute of Infectious Diseases and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa; Department of Psychiatry and MRC Unit on Risk & Resilience, University of Cape Town, Cape Town, South Africa.
⁶ Department of Psychiatry and MRC Unit on Risk & Resilience, University of Cape Town, Cape Town, South Africa; Groote Schuur Hospital, Cape Town, South Africa.

PMID: 30529765
DOI: 10.1016/j.comppsych.2018.11.014

Abstract

Background: Genome wide association studies (GWAS) of schizophrenia allow the generation of Polygenic Risk Scores (PRS). PRS can be used to determine the contribution to altered brain structures in this disorder, which have been well described. However, findings from studies using PRS to predict brain structural changes in schizophrenia have been inconsistent. We therefore performed a systematic review to determine the association between schizophrenia PRS and brain structure.

Methods: Following PRISMA systematic review guidelines, databases were searched for literature using key search terms. Inclusion criteria for the discovery sample required case-control schizophrenia GWAS summary statistics from European populations. The target sample was required to be of European ancestry, and have brain structure and genotype information. Quality assessment of the publications was conducted using the Mixed Methods Appraisal Tool for quantitative non-randomised studies.

Main findings: A total of seven studies were found to be eligible for review. Five studies found no significant association and two studies found a significant association of schizophrenia PRS with total brain, reduced white matter volume, and globus pallidus volume. However, the latter studies were conducted using smaller discovery (n_cases = 9394 n_controls = 12,462) and target samples compared to the studies with substantially larger discovery (n_cases = 33,636 n_controls = 43,008) and target samples where no association was observed. Taken together, the results suggest that schizophrenia PRS are not significantly associated with brain structural changes in this disorder.

Conclusions: The lack of significant association between schizophrenia PRS and brain structural changes may indicate that intermediate phenotypes other than brain structure should be the focus of future work. Alternatively, however, the lack of association found here may point to limitations of the current evidence-base, and so point to the need for future better powered studies.

Keywords: Polygenic risk score; brain structure; schizophrenia.

Publication types

Systematic Review

MeSH terms

Brain / diagnostic imaging*
Case-Control Studies
Female
Genetic Predisposition to Disease / genetics*
Genome-Wide Association Study / methods
Genotype
Humans
Male
Multifactorial Inheritance / genetics*
Phenotype
Risk Factors
Schizophrenia / diagnostic imaging*
Schizophrenia / genetics*