A genome-wide linkage scan of bipolar disorder in Latino families identifies susceptibility loci at 8q24 and 14q32

Authors

  • Suzanne Gonzalez,

    1. Center of Excellence for Neurosciences, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, Texas
    2. Department of Psychiatry, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, Texas
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  • Cynthia Camarillo,

    1. Center of Excellence for Neurosciences, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, Texas
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  • Marco Rodriguez,

    1. Center of Excellence for Neurosciences, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, Texas
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  • Mercedes Ramirez,

    1. Center of Excellence for Neurosciences, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, Texas
    2. Department of Psychiatry, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, Texas
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  • Juan Zavala,

    1. Center of Excellence for Neurosciences, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, Texas
    2. Department of Psychiatry, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, Texas
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  • Regina Armas,

    1. Langley Porter Psychiatric Institute, University of California at San Francisco, San Francisco, California
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  • Salvador A. Contreras,

    1. Department of Psychiatry, University of Texas Health Science Center at San Antonio, San Antonio, Texas
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  • Javier Contreras,

    1. Centro de Investigación en Biología Celular y Molecular y Escuela de Biologia, Universidad de Costa Rica, San Jose, Costa Rica
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  • Albana Dassori,

    1. Department of Psychiatry, University of Texas Health Science Center at San Antonio, San Antonio, Texas
    2. South Texas Veterans Health Care System, San Antonio, Texas
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  • Laura Almasy,

    1. Department of Genetics, Texas Biomedical Research Institute, San Antonio, Texas
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  • Deborah Flores,

    1. Los Angeles Biomedical Research Center at Harbor, University of California Los Angeles Medical Center, Torrance, California
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  • Alvaro Jerez,

    1. Centro Internacional de Trastornos Afectivos y de la Conducta Adictiva, Guatemala, Guatemala
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  • Henriette Raventós,

    1. Centro de Investigación en Biología Celular y Molecular y Escuela de Biologia, Universidad de Costa Rica, San Jose, Costa Rica
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  • Alfonso Ontiveros,

    1. Instituto de Información e Investigación en Salud Mental AC, Monterrey, Nuevo Leon, Mexico
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  • Humberto Nicolini,

    1. Grupo de Estudios Médicos y Familiares Carracci, S.C., México, D.F., Mexico
    2. Instituto Nacional de Medicina Genómica, México, D.F., Mexico
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  • Michael Escamilla

    Corresponding author
    1. Center of Excellence for Neurosciences, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, Texas
    2. Department of Psychiatry, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, Texas
    • Correspondence to:

      Michael Escamilla, MD, Department of Psychiatry Paul L. Foster School of Medicine Texas Tech University Health Science Center 4800 Alberta El Paso, TX 79905, USA

      E-mail: m.escamilla@ttuhsc.edu

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Abstract

A genome-wide nonparametric linkage screen was performed to localize Bipolar Disorder (BP) susceptibility loci in a sample of 3757 individuals of Latino ancestry. The sample included 963 individuals with BP phenotype (704 relative pairs) from 686 families recruited from the US, Mexico, Costa Rica, and Guatemala. Non-parametric analyses were performed over a 5 cM grid with an average genetic coverage of 0.67 cM. Multipoint analyses were conducted across the genome using non-parametric Kong & Cox LOD scores along with Sall statistics for all relative pairs. Suggestive and significant genome-wide thresholds were calculated based on 1000 simulations. Single-marker association tests in the presence of linkage were performed assuming a multiplicative model with a population prevalence of 2%. We identified two genome-wide significant susceptibly loci for BP at 8q24 and 14q32, and a third suggestive locus at 2q13-q14. Within these three linkage regions, the top associated single marker (rs1847694, P = 2.40 × 10−5) is located 195 Kb upstream of DPP10 in Chromosome 2. DPP10 is prominently expressed in brain neuronal populations, where it has been shown to bind and regulate Kv4-mediated A-type potassium channels. Taken together, these results provide additional evidence that 8q24, 14q32, and 2q13-q14 are susceptibly loci for BP and these regions may be involved in the pathogenesis of BP in the Latino population. © 2014 Wiley Periodicals, Inc.

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