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Clinical Trial
. 2009 Jun;166(6):718-25.
doi: 10.1176/appi.ajp.2009.08111633. Epub 2009 May 15.

A genomewide association study of response to lithium for prevention of recurrence in bipolar disorder

Roy H Perlis  1 , Jordan W Smoller, Manuel A R Ferreira, Andrew McQuillin, Nick Bass, Jacob Lawrence, Gary S Sachs, Vishwajit Nimgaonkar, Edward M Scolnick, Hugh Gurling, Pamela Sklar, Shaun Purcell
Affiliations
Clinical Trial

A genomewide association study of response to lithium for prevention of recurrence in bipolar disorder

Roy H Perlis et al. Am J Psychiatry. 2009 Jun.

Abstract

Objective: Lithium remains a first-line treatment for bipolar disorder, but the mechanisms by which it prevents the recurrence of mood episodes are not known. The authors utilized data from a genomewide association study to examine associations between single nucleotide polymorphisms (SNPs) and the outcome of lithium treatment in two cohorts of patients with bipolar I disorder or bipolar II disorder.

Method: The hazard for mood episode recurrence was examined among 1,177 patients with bipolar I disorder or bipolar II disorder, including 458 individuals treated with lithium carbonate or citrate, who were participants in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) cohort. SNPs showing the greatest evidence of association in Cox regression models were then examined for association with positive lithium response among 359 bipolar I or II disorder patients treated with lithium carbonate or citrate in a second cohort from the University College London.

Results: The strongest association in the STEP-BD cohort (minimum p=5.5 x 10(-7)) was identified for a region on chromosome 10p15 (rs10795189). Of the regions showing suggestive evidence (p<5 x 10(-4)) of association with lithium response, five were further associated with positive lithium response in the University College London cohort, including SNPs in a region on chromosome 4q32 spanning a gene coding for the glutamate/alpha-amino-3-hydroxy-5-methyl-4-isoxazolpropionate (AMPA) receptor GRIA2.

Conclusions: Multiple novel loci merit further examination for association with lithium response in bipolar disorder patients, including one region that spans the GRIA2 gene, for which expression has been shown to be regulated by lithium treatment.

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Figures

FIGURE 1
FIGURE 1
Consolidated Standards of Reporting Trials (CONSORT) Diagram Illustrating the Derivation of the STEP-BD Pharmacogenetic Recurrence Cohort
FIGURE 2
FIGURE 2
Survival Analysis of rs9784453 Among Lithium-Treated Subjects and the Full-Recurrence Cohort
FIGURE 3
FIGURE 3
Genomewide Association Results for Time to Recurrence Among Lithium-Treated Subjects and All Subjects
See this image and copyright information in PMC

Comment in

  • New hope for pharmacogenetic testing.
    Nurnberger JI Jr. Nurnberger JI Jr. Am J Psychiatry. 2009 Jun;166(6):635-8. doi: 10.1176/appi.ajp.2009.09040536. Am J Psychiatry. 2009. PMID: 19487397 No abstract available.

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