GTR Home > Conditions/Phenotypes > Schizophrenia


Schizophrenia is highly heritable, as shown by family, twin, and adoption studies. For example, for identical twins, if one twin develops schizophrenia, the other twin has about a 50% chance of also developing the disease. The risk of the general population developing the schizophrenia is about 0.3-0.7% worldwide. The search for “schizophrenia genes” has been elusive. Initial linkage studies looked at parts of the genome associated with schizophrenia, and many candidate genes were identified, including APOE, COMT, DAO, DRD1, DRD2, DRD4, DTNBP1, GABRB2, GRIN2B, HP, IL1B, MTHFR, PLXNA2, SLC6A4, TP53, and TPH1. However, some of these have later been questioned. Microdeletions and microduplications have been found to be three times more common in individuals with schizophrenia, compared to controls. Because these deletions and duplications are in genes that are overexpressed in pathways related to brain development, it is possible that the inheritance of multiple rare variants may contribute to the development of schizophrenia. Several genetic disorders feature schizophrenia as a clinical feature. The 22q11.2 Deletion Syndrome comprises many different syndromes, of which one of the most serious is DiGeorge syndrome. Children born with DiGeorge syndrome typically have heart defects, cleft palate, learning difficulties, and immune deficiency. Schizophrenia is a late manifestation, affecting around 30% of individuals. Microdeletions and duplications in chromosome 1, 2, 3, 7, 15 and 16 have also been associated with schizophrenia. In 2014, a genome-wide association study looked at the genomes of over 35,000 patients and 110,00 controls. The study identified 108 SNPs that were associated with schizophrenia, 83 of which had not been previously reported. As expected, many of these loci occurred in genes that are expressed in the brain. For example, the SNPs included a gene that encodes the dopamine D2 receptor, DRD2 (the target of antipsychotic drugs), and many genes involved in glutamine neurotransmitter pathways and synaptic plasticity (e.g., GRM3, GRIN2A, SRR, GRIA1). More surprisingly, however, associations were also enriched among genes expressed in tissues with important immune functions. In 2016, a study based on nearly 65,000 people investigated the association between schizophrenia and variation in the Major Histocompatibility Complex (MHC) locus—a region on chromosome 6 that is important for immune function. The study focused on the C4 gene (complement component 4) that exists as two distinct genes: C4A and C4B, which encode particularly structurally diverse alleles. The study found that the alleles which promoted greater expression of C4A in the brain were associated with a greater risk of schizophrenia. By using mice models, the study showed that C4 is involved in the elimination of synapses during brain maturation. In humans, “synaptic pruning” is most active during late adolescence, which coincides with the typical onset of symptoms of schizophrenia. It is therefore possible that the inheritance of specific C4A alleles could lead to “run away” synaptic pruning, increasing the risk of schizophrenia. Further research may even determine C4 as a potential therapeutic target. [from Medical Genetics Summaries]

Available tests

41 tests are in the database for this condition.

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Genes See tests for all associated and related genes

    Summary: AKT serine/threonine kinase 1

  • Also known as: APOL-II, APOL3, APOL2
    Summary: apolipoprotein L2

  • Also known as: APOL-IV, APOLIV, APOL4
    Summary: apolipoprotein L4

  • Also known as: ASRT7, CGP-39, GP-39, GP39, HC-gp39, HCGP-3P, YK-40, YKL-40, YKL40, YYL-40, hCGP-39, CHI3L1
    Summary: chitinase 3 like 1

  • Also known as: HEL-S-98n, COMT
    Summary: catechol-O-methyltransferase

  • Also known as: LG72, SG72, DAOA
    Summary: D-amino acid oxidase activator

  • Also known as: DISC1-AS1, DISC1OS, NCRNA00015, DISC2
    Summary: disrupted in schizophrenia 2

  • Also known as: D3DR, ETM1, FET1, DRD3
    Summary: dopamine receptor D3

  • Also known as: 5-HT2A, HTR2, HTR2A
    Summary: 5-hydroxytryptamine receptor 2A

  • Also known as: , MTHFR
    Summary: methylenetetrahydrofolate reductase

  • Also known as: NGR, NOGOR, RTN4R
    Summary: reticulon 4 receptor

  • Also known as: SYNII, SYN2
    Summary: synapsin II

Clinical features


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