Genetic association analysis of serotonin system genes in bipolar affective disorder

Am J Psychiatry. 1999 Jan;156(1):136-8. doi: 10.1176/ajp.156.1.136.


Objective: This study examined the putative role of serotonin genes in the etiology of bipolar affective disorder.

Method: Genetic association analysis was performed for individuals with bipolar affective disorder and unaffected subjects closely matched in age, sex, and ethnic background (N=103 in each group). The allele and genotype frequencies of polymorphisms at the genes for serotonin receptors HTR1A, HTR1Dalpha, HTR1Dbeta, HTR2A, HTR2C, HTR7, tryptophan hydroxylase (TPH), and the serotonin transporter (hSERT) were compared in the two groups of subjects.

Results: Statistically significant positive associations were found for HTR2A and hSERT polymorphisms. However, results from an independent replication group of over 100 patients with bipolar affective disorder and their matched comparison subjects failed to confirm these associations.

Conclusions: These results suggest that the serotonin genes studied are not associated with bipolar affective disorder, although transmission disequilibrium studies are required in order to confirm this conclusion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Bipolar Disorder / enzymology
  • Bipolar Disorder / genetics*
  • Carrier Proteins / genetics
  • Female
  • Gene Frequency
  • Genotype
  • Haplotypes
  • Humans
  • Male
  • Membrane Glycoproteins / genetics
  • Membrane Transport Proteins*
  • Nerve Tissue Proteins*
  • Odds Ratio
  • Polymorphism, Genetic
  • Receptors, Serotonin / genetics
  • Reproducibility of Results
  • Serotonin / genetics*
  • Serotonin Plasma Membrane Transport Proteins
  • Tryptophan Hydroxylase / genetics


  • Carrier Proteins
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • Receptors, Serotonin
  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin
  • Tryptophan Hydroxylase