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Human Molecular Genetics Advance Access published online on September 19, 2006
Human Molecular Genetics, doi:10.1093/hmg/ddl254
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© The Author 2006. Published by Oxford University Press. All rights reserved
Received June 29, 2006
Revised August 14, 2006
Accepted September 8, 2006

Article

Convergent linkage evidence from two Latin American population isolates supports the presence of a susceptibility locus for bipolar disorder in 5q31-34

Ibi Herzberg 1, Anna Jasinska 2, Jenny Garcia 3, Damini Jawaheer 2, Susan Service 2, Barbara Kremeyer 1, Constanza Duque 4, Maria V. Parra 4, Jorge Vega 4, Daniel Ortiz 4, Luis Carvajal 1, Guadalupe Polanco 1, Gabriel J. Restrepo 3, Carlos Lopez 3, Carlos Palacio 3, Matthew Levinson 2, Ileana Aldana 2, Carol Mathews 5, Pablo Davanzo 6, Julio Molina 2, Eduardo Fournier 7, Julio Bejarano 7, Magui Ramirez 7, Carmen Araya Ortiz 7, Xinia Araya 7, Chiara Sabatti 8, Victor Reus 5, Gabriel Macaya 7, Gabriel Bedoya 4, Jorge Ospina 3, Nelson Freimer 9, and Andrés Ruiz-Linares 10 *

1 Galton Laboratory, Department of Biology, University College London, UK
2 Center for Neurobehavioral Genetics, University of California, Los Angeles, California USA
3 Departamento de Psiquiatría, Universidad de Antioquia, Medellín, Colombia
4 Laboratorio de Genética Molecular, Universidad de Antioquia, Medellín, Colombia
5 Department of Psychiatry, University of California San Francisco, San Francisco, California USA 94143
6 Department of Psychiatry and Behavioral Sciences, School of Medicine, University of California, Los Angeles, California USA 90095
7 Cell and Molecular Biology Research Center and Escuela de Medicina, Universidad de Costa Rica, San Jose, Costa Rica
8 Department of Human Genetics, University of California, Los Angeles, California USA 90095; Department of Statistics, University of California, Los Angeles, California USA 90095
9 Center for Neurobehavioral Genetics, University of California, Los Angeles, California USA.; Department of Psychiatry and Behavioral Sciences, School of Medicine, University of California, Los Angeles, California USA 90095; The Jane and Terry Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, California USA 90095
10 Galton Laboratory, Department of Biology - Wolfson House, University College London, 4 Stephenson Way, London NW1 2HE, UK; Laboratorio de Genética Molecular, Universidad de Antioquia, Medellín, Colombia

* To whom correspondence should be addressed.
Andrés Ruiz-Linares, E-mail: a.ruizlin{at}ucl.ac.uk


  Abstract

We performed a whole genome microsatellite marker scan in six families with bipolar mood disorder (BP) ascertained in Antioquia, a historically isolated population from North West Colombia. These families were characterized clinically using the approach employed in independent ongoing studies of BP in the closely related population of the Central Valley of Costa Rica. The most consistent linkage results from parametric and non-parametric analyses of the Colombian scan involved markers on 5q31-33, a region implicated by previous studies of BP. Because of these concordant results, a follow-up study with additional markers was undertaken in an expanded set of Colombian and Costa Rican families; this provided genome-wide significant evidence of linkage of BPI to a candidate region of ~10 cM in 5q31-33 (maximum NPL score = 4.395, P<0.00004). Interestingly, this region has been implicated in several previous genetic studies of schizophrenia and psychosis, including disease association with variants of the enthoprotin and gamma-aminobutyric acid receptor genes.


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