Overlap between genetic variants associated with schizophrenia spectrum disorders and intelligence quotient: a systematic review

Abstract

Background: To study whether there is genetic overlap underlying the risk for schizophrenia spectrum disorders (SSDs) and low intelli-gence quotient (IQ), we reviewed and summarized the evidence on genetic variants associated with both traits. Methods: We performedthis review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and preregistered it inPROSPERO. We searched the Medline databases via PubMed, PsycInfo, Web of Science and Scopus. We included studies in adultswith a diagnosis of SSD that explored genetic variants (single nucleotide polymorphisms [SNPs], copy number variants [CNVs], genomicinsertions or genomic deletions), estimated IQ and studied the relationship between genetic variability and both traits (SSD and IQ). Wesynthesized the results and assessed risk of bias using the Quality of Genetic Association Studies (Q-Genie) tool. Results: Fifty-five studiesmet the inclusion criteria (45 case?control, 9 cross-sectional, 1 cohort), of which 55% reported significant associations for genetic variantsinvolved in IQ and SSD. The SNPs more frequently explored through candidate gene studies were in COMT, DTNBP1, BDNF and TCF4.Through genome-wide association studies, 2 SNPs in CHD7 and GATAD2A were associated with IQ in patients with SSD. The studies onCNVs suggested significant associations between structural variants and low IQ in patients with SSD. Limitations: Overall, primary studiesused heterogeneous IQ measurement tools and had small samples. Grey literature was not screened. Conclusion: Genetic overlap be-tween SSD and IQ supports the neurodevelopmental hypothesis of schizophrenia. Most of the risk polymorphisms identified were ingenes relevant to brain development, neural proliferation and differentiation, and synaptic plasticity.