Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Arch Gen Psychiatry. 2008 Jan;65(1):53-61. doi: 10.1001/archgenpsychiatry.2007.15.

Family-based association study of lithium-related and other candidate genes in bipolar disorder.

Author information

  • 1Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, 185 Cambridge St, Boston, MA 02114, USA.

Abstract

CONTEXT:

Association studies in bipolar disorder have been focused on a relatively narrow pool of candidate genes based on a limited understanding of the underlying pathophysiologic features. Recent developments suggest that a broader pool of genes may be associated with this disorder.

OBJECTIVE:

To examine the association between genes related to the lithium mechanism of action, as well as other positional and functional candidates, with bipolar I disorder.

DESIGN:

We examined a dense set of haplotype-tagging single-nucleotide polymorphisms using a gene-based test of association.

PARTICIPANTS:

Three hundred seventy-nine parent-affected offspring trios.

RESULTS:

No genes specifically chosen to probe the action of lithium were associated with bipolar disorder. However, gene-based analysis of sialyltransferase 4A (SIAT4A), tachykinin receptor 1 (TACR1), and gamma-aminobutyric acid(A) beta2 receptor subunit (GABRB2) yielded evidence of association (empirical P value, <.005). Among 3 genes associated with schizophrenia or bipolar disorder in multiple previous studies, including dysbindin (DTNBP1), neuregulin (NRG1), and disrupted-in-schizophrenia 1 (DISC1), only DISC1 showed evidence of association in this cohort. In a secondary analysis of these 6 genes among parent-proband trios with a history of psychosis, evidence of the association with SIAT4A was strengthened.

CONCLUSIONS:

These results suggest novel candidates and 1 gene (DISC1) previously associated with schizophrenia that merit further study in bipolar disorder. However, polymorphisms in major lithium-signaling genes do not appear to contribute substantially to bipolar liability.

PMID:
18180429
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Silverchair Information Systems
    Loading ...
    Write to the Help Desk