Journal of Affective Disorders 58 (2000) 63–68 www.elsevier.com / locate / jad Brief report Polyglutamine coding genes in bipolar disorder: lack of association with selected candidate loci a, b, c c a a c c * ` G. Turecki , M. Alda , P. Grof , R. Joober , R. Lafreniere , P. Cavazzoni , A. Duffy , c d d d e ¨ ¨ ´ ´ E. Grof , B. Ahrens , A. Berghofer , B. Muller-Oerlinghausen , M. Dvorakova , e e e f f g ´ ´ ´ E. Libigerova , M. Vojtechovsky , P. Zvolsky , A. Nilsson , H. Prochazka , R.W. Licht , g g g h h h N.A. Rasmussen , M. Schou , P. Vestergaard , A. Holzinger , C. Schumann , K. Thau , a G.A. Rouleau a Centre for Research in Neuroscience, The Montreal General Hospital, McGill University, 1650 Cedar Ave, Montreal H3G 1A4, Canada b Department of Psychiatry, Dalhousie University, Halifax, Canada c Department of Psychiatry, University of Ottawa, Ottawa, Canada d Department of Psychiatry, Free University, Berlin, Germany e ´ ´ Department of Psychiatry, Charles University, Prague and Hradec Kralove, Czech Republic f Karsudden Hospital, Katrineholm, Sweden g ˚ Psychiatric Hospital, University of Arhus, Risskov, Denmark h University Clinic of Vienna, Department of Psychiatry, Vienna, Austria Received 16 December 1998; accepted 12 March 1999 Abstract Background: Several studies have suggested that expanded trinucleotide repeats, particularly CAG, may have a role in the etiology of BD. Results obtained with the repeat expansion detection technique (RED) have indicated that bipolar patients have an excess of expanded CAG repeats. However, it is not clear which loci account for this difference. Methods: Using lithium-responsive bipolar patients in order to reduce heterogeneity, we investigated five loci that are expressed in the brain and contain translated CAG repeats. A sample of 138 cases and 108 controls was studied. Genotypes were coded quantitatively or qualitatively and repeat distributions were compared. Results: No difference was found in allele distribution between cases and controls for any of the loci studied. In one locus — L10378 — patients had a tendency to present shorter alleles (28.1 versus 27.9 repeats; t 5 2.55, df 5 205, P 5 0.011), however, this difference disappeared after correction for multiple testing. Limitations: The study has limitations common to most candidate gene association studies, that is, limited number of loci investigated and limited power to detect loci that account for a small proportion of the total genetic variability. Conclusions: Our results suggest that the loci investigated have no major role in the genetic predisposition to bipolar disorder. 2000 Elsevier Science B.V. All rights reserved. Keywords: Trinucleotide repeats; Bipolar disorder; Lithium response; Association studies *Corresponding author. Tel.: 1 1-514-937-6011, ext. 2524; fax: 1 1-514-934-8265. E-mail address: gustavo@bagel.epi.mcgill.ca (G. Turecki) 0165-0327 / 00 / $ – see front matter 2000 Elsevier Science B.V. All rights reserved. PII: S0165-0327(99)00074-9