Human Genetics

, Volume 111, Issue 6, pp 521–537

Population variation in linkage disequilibrium across the COMT gene considering promoter region and coding region variation

  • Mellissa M. DeMille
  • Judith R. Kidd
  • Valeria Ruggeri
  • Meg A. Palmatier
  • David Goldman
  • Adekunle Odunsi
  • Friday Okonofua
  • Elena Grigorenko
  • Leslie O. Schulz
  • Batsheva Bonne-Tamir
  • Ru-Band Lu
  • Josef Parnas
  • Andrew J. Pakstis
  • Kenneth K. Kidd
Original Investigation

DOI: 10.1007/s00439-002-0809-0

Cite this article as:
DeMille, M.M., Kidd, J.R., Ruggeri, V. et al. Hum Genet (2002) 111: 521. doi:10.1007/s00439-002-0809-0

Abstract.

Catechol-O-methyl transferase (COMT) catalyzes the first step in one of the major pathways in the degradation of catecholamines. The COMT gene on chromosome 22 has been considered a candidate gene for many neuropsychiatric disorders, in part because an exon 4 single nucleotide polymorphism (SNP) in COMT causes an amino acid substitution associated with significantly altered enzyme activity. This functional variant, detected as an NlaIII restriction site polymorphism (RSP), is polymorphic in populations from around the world. A four-site haplotype spanning 28 kb effectively encompasses COMT. This haplotype is comprised of two novel polymorphisms [a tetranucleotide short tandem repeat polymorphism (STRP) in intron 1 and a HindIII RSP at the 5′ end of COMT], the NlaIII site, and another previously published site – a BglI RSP at the 3′ end of the gene. Overall linkage disequilibrium (LD) for this haplotype is strong and significant in 32 population samples from around the world. Conditional probabilities indicate that, in spite of moderate to strong disequilibrium in most non-African populations, the NlaIII site, although often used for prediction, would not always be a reliable predictor of allelic variation at the other sites. Because other functional variation might exist, especially regulatory variation, these findings indicate that haplotypes would be more effective indicators of possible involvement of COMT in disease etiology.

Copyright information

© Springer-Verlag 2002

Authors and Affiliations

  • Mellissa M. DeMille
    • 1
  • Judith R. Kidd
    • 1
  • Valeria Ruggeri
    • 1
  • Meg A. Palmatier
    • 1
  • David Goldman
    • 2
  • Adekunle Odunsi
    • 3
  • Friday Okonofua
    • 4
  • Elena Grigorenko
    • 5
  • Leslie O. Schulz
    • 6
  • Batsheva Bonne-Tamir
    • 7
  • Ru-Band Lu
    • 8
  • Josef Parnas
    • 9
  • Andrew J. Pakstis
    • 1
  • Kenneth K. Kidd
    • 1
  1. 1.Department of Genetics, Yale University School of Medicine, New Haven, CT 06520-8005, USA
  2. 2.Neurogenetics Laboratory, NIAAA, Park Building Room 451, 12420 Parklawn Drive, Rockville, MD 20852, USA
  3. 3.Department of Gynecological Oncology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA
  4. 4.Department of Obstetrics and Gynecology, Faculty of Medicine, University of Benin, Benin City, Nigeria
  5. 5.Department of Psychology, Yale University, New Haven CT 06511, USA
  6. 6.Department of Health Sciences, University of Wisconsin-Milwaukee, Milwaukee, WI 53201, USA
  7. 7.Department of Genetics, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
  8. 8.Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China
  9. 9.Copenhagen University, Psychiatry Department, Hvidovre Hospital, Kettegard Alle 30, Hvidovre, Denmark