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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 12qKremeyer 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 Corresponding Author
Research Department of Genetics, Evolution and Environment
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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.
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