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Related Experiment Videos

Two commonly expanded CAG/CTG repeat loci: involvement in affective disorders?

K Lindblad1, P O Nylander, C Zander

  • 1Department of Molecular Medicine, Karolinska Institute, Stockholm, Sweden.

Molecular Psychiatry
|October 17, 1998
PubMed
Summary

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Expanded CTG18.1 trinucleotide repeat expansions are linked to bipolar disorder, suggesting a genetic vulnerability. The ERDA1 locus showed no association with affective disorders in this study.

Area of Science:

  • Genetics
  • Neuroscience
  • Psychiatry

Background:

  • Trinucleotide repeat expansions (TRE) have been associated with bipolar affective disorder.
  • Previous studies utilized the repeat expansion detection (RED) method to identify these associations.

Purpose of the Study:

  • To investigate the specific genetic loci, ERDA1 and CTG18.1, associated with trinucleotide repeat expansions in bipolar disorder.
  • To determine if CTG18.1 expansions act as a vulnerability factor for affective disorders.

Main Methods:

  • Analysis of RED products (>120 nt) in affective disorder patients, family members, and controls.
  • Polymerase Chain Reaction (PCR) to assess CTG18.1 and ERDA1 expansions.
  • Statistical analysis to compare expansion frequencies and size distributions between affected and unaffected individuals.

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Main Results:

  • 89% of large RED products correlated with expansions at ERDA1 and CTG18.1 loci.
  • CTG18.1 expansions were more frequent in bipolar patients (13%) than controls (5%) (P < 0.07) and showed different size distributions (P < 0.03).
  • Affected offspring in families with anticipation had significantly higher CTG18.1 expansion frequencies (P < 0.04) and earlier onset with longer expansions (rs = -0.3, P = 0.05). ERDA1 expansions showed no significant association.

Conclusions:

  • Expanded alleles at the CTG18.1 locus significantly increase the risk (odds ratio 2.6-2.8) for affective disorder, acting as a potential vulnerability factor.
  • The ERDA1 locus appears unrelated to affective disorder susceptibility.
  • CTG18.1 expansions are associated with earlier age-of-onset in bipolar disorder.