TDT: Advantages & disadvantages for mapping studies of schizophrenia

K. V. Chowdari, Z. Feng, B. Allison, J. Wood, I. Gottesman, A. Chakravarti, V. L. Nimgaonkar

Research output: Contribution to journalArticle

Abstract

Association studies of schizophrenia using unrelated controls are prone to artifacts due to population sub-structure. Family based analyses such as the Transmission Disequilibrium Test (TDT) are therefore currently preferred. However, the TDT imposes restrictions regarding family structure and parental genotype. This limits its usefulness, as shown in our ongoing studies. We evaluated 168 simplex families consisting of patients with schizophrenia (DSM-IV criteria) and available parents at the following candidate genes /regions: cPLA2, DRD1, DRD3, hSKCaS, DCP1, CHRNA7, D22S278 and chromosome 6p21.3. We did not detect significant preferential transmission of any allele from heterozygous parents to affected offspring. The requirement of heterozygoous parents for the TDT, as well as exclusion of families with single homozygous parents resulted in substantial numbers of exclusions. For example, only 58 parental genotypes were included when a restriction fragment length polymorphism (RFLP) at DRD3 was investigated using the computer software MCETDT. Haplotype based TDT analysis using '3,4', a short tandem repeat polymorphism (STRP) localized <1 kb from the DRD3 RFLP did not increase informativeness. It may be advisable to use the TDT in conjunction with analysis using unrelated controls. This is illustrated with respect to DCP1, for which we examined a bi-allelic polymorphism simultaneously among two independent sets of unrelated controls.

Original languageEnglish (US)
Number of pages1
JournalAmerican Journal of Medical Genetics - Neuropsychiatric Genetics
Volume96
Issue number4
StatePublished - Aug 7 2000

ASJC Scopus subject areas

  • Genetics(clinical)
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'TDT: Advantages & disadvantages for mapping studies of schizophrenia'. Together they form a unique fingerprint.

  • Cite this

    Chowdari, K. V., Feng, Z., Allison, B., Wood, J., Gottesman, I., Chakravarti, A., & Nimgaonkar, V. L. (2000). TDT: Advantages & disadvantages for mapping studies of schizophrenia. American Journal of Medical Genetics - Neuropsychiatric Genetics, 96(4).