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wollet2
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The Psychiatric Risk Gene Transcription Factor 4 (TCF4) Regulates Neurodevelopmental Pathways Associated With Schizophrenia, Autism, and Intellectual Disability
Genetic variants in and around the transcription factor 4 (TCF4) gene are associated with range of disorders that are frequently associated with cognitive dysfunction.1–3 The most recent schizophrenia GWAS reported three independent single nucleotide polymorphisms (SNPs) in TCF4 that surpassed the threshold for genome wide significance.4 Intriguingly, rare TCF4 single nucleotide variants (SNVs) have also been described in schizophrenia patients, although their impact on the function of the protein has not been established.5,6 In addition to the genetic studies in schizophrenia, TCF4 variants are associated with early information processing and cognitive markers, some of which are schizophrenia endophenotypes.7–10 Damaging TCF4 mutations have also been described in large-scale genotyping studies in patients with ID, neurodevelopmental disorders, and most recently ASD.11–15 Haploinsufficiency of TCF4 causes Pitt–Hopkins syndrome (PTHS); a rare form intellectual disability (ID) associated with characteristic facial features, autonomic dysfunction, and behavioral traits that resemble autism spectrum disorder (ASD).16–19 Collectively, these studies implicate TCF4 in a range of neurodevelopmental disorders.
| Population | Group | Sample Size | Ref Allele | Alt Allele |
|---|
| Population | Group | Sample Size | Ref Allele | Alt Allele |
|---|---|---|---|---|
| Total | Global | 97800 | A=0.93291 | C=0.06709, G=0.00000 |
| European | Sub | 80228 | A=0.94664 | C=0.05336, G=0.00000 |
| African | Sub | 6000 | A=0.8507 | C=0.1493, G=0.0000 |
| African Others | Sub | 202 | A=0.827 | C=0.173, G=0.000 |
| African American | Sub | 5798 | A=0.8515 | C=0.1485, G=0.0000 |
| Asian | Sub | 224 | A=1.000 | C=0.000, G=0.000 |
| East Asian | Sub | 184 | A=1.000 | C=0.000, G=0.000 |
| Other Asian | Sub | 40 | A=1.00 | C=0.00, G=0.00 |
| Latin American 1 | Sub | 222 | A=0.968 | C=0.032, G=0.000 |
| Latin American 2 | Sub | 1176 | A=0.9558 | C=0.0442, G=0.0000 |
| South Asian | Sub | 4918 | A=0.8015 | C=0.1985, G=0.0000 |