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Genomewide linkage analysis in Costa Rican families implicates chromosome 15q14 as a candidate region for OCD

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Abstract

Obsessive compulsive disorder (OCD) has a complex etiology that encompasses both genetic and environmental factors. However, to date, despite the identification of several promising candidate genes and linkage regions, the genetic causes of OCD are largely unknown. The objective of this study was to conduct linkage studies of childhood-onset OCD, which is thought to have the strongest genetic etiology, in several OCD-affected families from the genetically isolated population of the Central Valley of Costa Rica (CVCR). The authors used parametric and non-parametric approaches to conduct genome-wide linkage analyses using 5,786 single nucleotide repeat polymorphisms (SNPs) in three CVCR families with multiple childhood-onset OCD-affected individuals. We identified areas of suggestive linkage (LOD score ≥2) on chromosomes 1p21, 15q14, 16q24, and 17p12. The strongest evidence for linkage was on chromosome 15q14 (LOD = 3.13), identified using parametric linkage analysis with a recessive model, and overlapping a region identified in a prior linkage study using a Caucasian population. Each CVCR family had a haplotype that co-segregated with OCD across a ~7 Mbp interval within this region, which contains 18 identified brain expressed genes, several of which are potentially relevant to OCD. Exonic sequencing of the strongest candidate gene in this region, the ryanodine receptor 3 (RYR3), identified several genetic variants of potential interest, although none co-segregated with OCD in all three families. These findings provide evidence that chromosome 15q14 is linked to OCD in families from the CVCR, and supports previous findings to suggest that this region may contain one or more OCD susceptibility loci.

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Acknowledgments

This research was performed at the University of California, San Francisco. This research was supported by Grants to CAM from the National Center for Research Resources (K23 RR015533), the National Alliance for Research on Schizophrenia and Affective Disorders, the Obsessive Compulsive Foundation, and The Althea Foundation.

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Authors and Affiliations

  1. Department of Psychiatry, University of California, San Francisco, 401 Parnassus Avenue, San Francisco, CA, 94143-0984, USA

    Jessica Ross, Brooke Sheppard & Carol A. Mathews

  2. Departments of Psychiatry and Human Genetics, University of Chicago, Chicago, IL, USA

    Judith Badner

  3. Departments of Psychiatry and Pediatrics, Hospital Nacional de Niños, San Josè, Costa Rica

    Helena Garrido, Paula Umaña & Eduardo Fournier

  4. Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA

    Denise A. Chavira

  5. Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA

    Marco Grados

  6. Genome Core Facility, Institute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA

    Jonathan M. Woo & Pamela Doo

  7. Department of Genetics, Scripps Genomic Medicine, La Jolla, CA, USA

    Sarah Shaw Murray

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  1. Jessica Ross
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  2. Judith Badner
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  3. Helena Garrido
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  4. Brooke Sheppard
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  5. Denise A. Chavira
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  9. Paula Umaña
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  10. Eduardo Fournier
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  11. Sarah Shaw Murray
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  12. Carol A. Mathews
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Correspondence to Carol A. Mathews.

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Ross, J., Badner, J., Garrido, H. et al. Genomewide linkage analysis in Costa Rican families implicates chromosome 15q14 as a candidate region for OCD. Hum Genet 130, 795–805 (2011). https://doi.org/10.1007/s00439-011-1033-6

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