Molecular Medicine

, Volume 13, Issue 7–8, pp 407–414 | Cite as

Analysis of TBX1 Variation in Patients with Psychotic and Affective Disorders

  • Birgit H. Funke
  • Todd Lencz
  • Christine T. Finn
  • Pamela DeRosse
  • G. David Poznik
  • Alex M. Plocik
  • John Kane
  • John Rogus
  • Anil K. Malhotra
  • Raju Kucherlapati


A significant portion of patients with 22q11 deletion syndrome (22q11DS) develop psychiatric disorders, including schizophrenia and other psychotic and affective symptoms, and the responsible gene/s are assumed to also play a significant role in the etiology of nonsyndromic psychiatric disease. The most common psychiatric diagnosis among patients with 22q11DS is schizophrenia, thought to result from neurotransmitter imbalances and also from disturbed brain development. Several genes in the 22q11 region with known or suspected roles in neurotransmitter metabolism have been analyzed in patients with isolated schizophrenia; however, their contribution to the disease remains controversial. Haploinsufficiency of the TBX1 gene has been shown to be sufficient to cause the core physical malformations associated with 22q11DS in mice and humans and via abnormal brain development could contribute to 22q11DS-related and isolated psychiatric disease. 22q11DS populations also have increased rates of psychiatric conditions other than schizophrenia, including mood disorders. We therefore analyzed variations at the TBX1 locus in a cohort of 446 white patients with psychiatric disorders relevant to 22q11DS and 436 ethnically matched controls. The main diagnoses included schizophrenia (n = 226), schizoaffective disorder (n = 67), bipolar disorder (n = 82), and major depressive disorder (n = 29). We genotyped nine tag SNPs in this sample but did not observe significant differences in allele or haplotype frequencies in any of the analyzed groups (all affected, schizophrenia and schizoaffective disorder, schizophrenia alone, and bipolar disorder and major depressive disorder) compared with the control group. Based on these results we conclude that TBX1 variation does not make a strong contribution to the genetic etiology of nonsyndromic forms of psychiatric disorders commonly seen in patients with 22q11DS.



This project was supported by grants HD034980-09 to RK, K23MH001760 to AKM, K01 MH65580 to TL, P30 MH60575 to JK, and a General Clinical Research Center (M01 RR18535). We thank the HPCGG Genotyping core for their fast and excellent service and Dr. Bernice Morrow for providing services to generate lymphoblastoid cell lines and DNA.


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Copyright information

© Feinstein Institute for Medical Research 2007

Authors and Affiliations

  • Birgit H. Funke
    • 1
  • Todd Lencz
    • 2
  • Christine T. Finn
    • 1
  • Pamela DeRosse
    • 2
  • G. David Poznik
    • 3
  • Alex M. Plocik
    • 1
  • John Kane
    • 2
  • John Rogus
    • 3
  • Anil K. Malhotra
    • 2
  • Raju Kucherlapati
    • 1
  1. 1.Laboratory for Molecular MedicineHarvard Partners Center for Genetics and GenomicsCambridge, BostonUSA
  2. 2.Psychiatry ResearchThe Zucker Hillside HospitalGlen OaksUSA
  3. 3.Joslin Diabetes CenterBostonUSA

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