Vol. 70, No. 4, 2010
Issue release date: February 2011
Open Access Gateway
Hum Hered 2010;70:255–268
Original Paper
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Genome-Wide Linkage Scan of Bipolar Disorder in a Colombian Population Isolate Replicates Loci on Chromosomes 7p21–22, 1p31, 16p12 and 21q21–22 and Identifies a Novel Locus on Chromosome 12q

Kremeyer B.a · García J.b · Müller H.a · Burley M.W.a · Herzberg I.a · Parra M.V.c · Duque C.c · Vega J.c · Montoya P.b · López M.C.b · Bedoya G.c · Reus V.d · Palacio C.b · López C.b · Ospina-Duque J.b · Freimer N.B.e–g · Ruiz-Linares A.a, c
aDepartment of Genetics, Evolution and Environment, University College London, London, UK; bGrupo de Investigación en Psiquiatría, Departamento de Psiquiatría, and cLaboratorio de Genética Molecular, Universidad de Antioquia, Medellín, Colombia; dDepartment of Psychiatry, University of California San Francisco, San Francisco, Calif., eCenter for Neurobehavioral Genetics, fDepartment of Psychiatry and Behavioral Sciences, School of Medicine, and gThe Jane and Terry Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Calif., USA
email Corresponding Author

 goto top of outline Key Words

  • Bipolar disorder
  • Psychiatric genetics
  • Whole-genome linkage analysis

 goto top of outline Abstract

Background/Aims: Bipolar disorder (BP) is a severe psychiatric illness, characterised by alternating episodes of depression and mania, which ranks among the top ten causes of morbidity and life-long disability world-wide. We have previously performed a whole-genome linkage scan on 6 pedigrees segregating severe BP from the well-characterised population isolate of Antioquia, Colombia. We recently collected genotypes for the same set of 382 autosomal microsatellite markers in 9 additional Antioquian BP pedigrees. Here, we report the analysis of the combined pedigree set. Methods: Linkage analysis using both parametric and nonparametric approaches was conducted for 3 different diagnostic models: severe BP only (BPI); mood disorders (BPI, BPII and major depression); and psychosis (operationally defined by the occurrence of at least 1 episode of hallucinations and/or delusions). Results and Conclusion: For BPI only, the most interesting result was obtained for chromosome 7p21.1–p22.2 under a recessive model of inheritance (heterogeneity LOD score = 2.80), a region that had previously been linked to BP in a study on Portuguese Island families. For both BPI and mood disorders, nonparametric analyses identified a locus on chromosome 12ct–q14 (nonparametric linkage = 2.55 and 2.35, respectively). This locus has not previously been reported as a candidate region for BP. Additional candidate regions were found on chromosomes 1p22–31 (mood disorders) and 21q21–22 (BPI), 2 loci that have repeatedly been implicated in BP susceptibility. Linkage analysis of psychosis as a phenotype identified candidate regions on chromosomes 2q24–31 and 16p12–q12. The finding on chromosome 16p is noteworthy because the same locus has been implicated by genome-wide association analyses of BP.

Copyright © 2010 S. Karger AG, Basel

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Barbara Kremeyer
Research Department of Genetics, Evolution and Environment
University College London, Wolfson House
4 Stephenson Way, London NW1 2HE (UK)
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 goto top of outline Article Information

Received: January 9, 2010
Accepted after revision: September 3, 2010
Published online: November 10, 2010
Number of Print Pages : 14
Number of Figures : 3, Number of Tables : 2, Number of References : 69

 goto top of outline Publication Details

Human Heredity (International Journal of Human and Medical Genetics)

Vol. 70, No. 4, Year 2010 (Cover Date: February 2011)

Journal Editor: Devoto M. (Philadelphia, Pa./Rome)
ISSN: 0001-5652 (Print), eISSN: 1423-0062 (Online)

For additional information: http://www.karger.com/HHE

Open Access License / Drug Dosage / Disclaimer

Open Access License: This is an Open Access article licensed under the terms of the Creative Commons Attribution-NonCommercial 3.0 Unported license (CC BY-NC) (www.karger.com/OA-license), applicable to the online version of the article only. Distribution permitted for non-commercial purposes only.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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