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From the Research Unit in Mental Illness, Valdecilla Biomedical Research Institute, Santander, Cantabria, Spain (Murillo-García, Barrio-Martínez, Ayesa-Arriola); the Department of Molecular Biology, Faculty of Medicine, University of Cantabria, Santander, Cantabria, Spain (Murillo-García, Ayesa-Arriola); the Faculty of Psychology, University Complutense of Madrid, Madrid, Spain (Barrio-Martínez); the Department of Psychology, Faculty of Health Sciences, University of Deusto, Bilbao, Basque Country, Spain (Setién-Suero); the Biomedical Research Networking Center for Mental Health (CIBERSAM), Madrid, Madrid, Spain (Soler, Papiol, Fatjó-Vilas, Ayesa-Arriola); the Departament de Biologia Evolutiva, Ecologia i Ciències Ambientals, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain (Soler, Fatjó-Vilas); the Institut de Biomedicina de la Universitat de Barcelona, Universitat de Barcelona, Barcelona, Spain (Soler); the Institute of Psychiatric Phenomics and Genomics, University Hospital, LMU Munich, Munich, Germany (Papiol); the Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany (Papiol); the FIDMAG Sisters Hospitallers Research Foundation, Sant Boi de Llobregat, Barcelona, Spain (Fatjó-Vilas)
Published: November 2022
AI Article Synopsis
Article Abstract
Background: To study whether there is genetic overlap underlying the risk for schizophrenia spectrum disorders (SSDs) and low intelligence quotient (IQ), we reviewed and summarized the evidence on genetic variants associated with both traits.
Methods: We performed this review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and preregistered it in PROSPERO. We searched the Medline databases via PubMed, PsycInfo, Web of Science and Scopus. We included studies in adults with a diagnosis of SSD that explored genetic variants (single nucleotide polymorphisms [SNPs], copy number variants [CNVs], genomic insertions or genomic deletions), estimated IQ and studied the relationship between genetic variability and both traits (SSD and IQ). We synthesized the results and assessed risk of bias using the Quality of Genetic Association Studies (Q-Genie) tool.
Results: Fifty-five studies met the inclusion criteria (45 case-control, 9 cross-sectional, 1 cohort), of which 55% reported significant associations for genetic variants involved in IQ and SSD. The SNPs more frequently explored through candidate gene studies were in , , and . Through genome-wide association studies, 2 SNPs in and were associated with IQ in patients with SSD. The studies on CNVs suggested significant associations between structural variants and low IQ in patients with SSD.
Limitations: Overall, primary studies used heterogeneous IQ measurement tools and had small samples. Grey literature was not screened.
Conclusion: Genetic overlap between SSD and IQ supports the neurodevelopmental hypothesis of schizophrenia. Most of the risk polymorphisms identified were in genes relevant to brain development, neural proliferation and differentiation, and synaptic plasticity.
