caa a22 4500 445860693 CHVBK 20180317145441.0 cr unu---uuuuu 170323e20111201xx s 000 0 eng 10.1007/s00439-011-1033-6 doi (NATIONALLICENCE)springer-10.1007/s00439-011-1033-6 Genomewide linkage analysis in Costa Rican families implicates chromosome 15q14 as a candidate region for OCD [Elektronische Daten] [Jessica Ross, Judith Badner, Helena Garrido, Brooke Sheppard, Denise Chavira, Marco Grados, Jonathan Woo, Pamela Doo, Paula Umaña, Eduardo Fournier, Sarah Murray, Carol Mathews] 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 ~7Mbp 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. Springer-Verlag, 2011 Ross Jessica Department of Psychiatry, University of California, San Francisco, 401 Parnassus Avenue, 94143-0984, San Francisco, CA, USA aut Badner Judith Departments of Psychiatry and Human Genetics, University of Chicago, Chicago, IL, USA aut Garrido Helena Departments of Psychiatry and Pediatrics, Hospital Nacional de Niños, San Josè, Costa Rica aut Sheppard Brooke Department of Psychiatry, University of California, San Francisco, 401 Parnassus Avenue, 94143-0984, San Francisco, CA, USA aut Chavira Denise Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA aut Grados Marco Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA aut Woo Jonathan Genome Core Facility, Institute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA aut Doo Pamela Genome Core Facility, Institute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA aut Umaña Paula Departments of Psychiatry and Pediatrics, Hospital Nacional de Niños, San Josè, Costa Rica aut Fournier Eduardo Departments of Psychiatry and Pediatrics, Hospital Nacional de Niños, San Josè, Costa Rica aut Murray Sarah Department of Genetics, Scripps Genomic Medicine, La Jolla, CA, USA aut Mathews Carol Department of Psychiatry, University of California, San Francisco, 401 Parnassus Avenue, 94143-0984, San Francisco, CA, USA aut Human Genetics Springer-Verlag 130/6(2011-12-01), 795-805 0340-6717 130:6<795 2011 130 439 https://doi.org/10.1007/s00439-011-1033-6 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00439-011-1033-6 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Ross Jessica Department of Psychiatry, University of California, San Francisco, 401 Parnassus Avenue, 94143-0984, San Francisco, CA, USA aut NATIONALLICENCE 700 1- Badner Judith Departments of Psychiatry and Human Genetics, University of Chicago, Chicago, IL, USA aut NATIONALLICENCE 700 1- Garrido Helena Departments of Psychiatry and Pediatrics, Hospital Nacional de Niños, San Josè, Costa Rica aut NATIONALLICENCE 700 1- Sheppard Brooke Department of Psychiatry, University of California, San Francisco, 401 Parnassus Avenue, 94143-0984, San Francisco, CA, USA aut NATIONALLICENCE 700 1- Chavira Denise Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA aut NATIONALLICENCE 700 1- Grados Marco Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA aut NATIONALLICENCE 700 1- Woo Jonathan Genome Core Facility, Institute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA aut NATIONALLICENCE 700 1- Doo Pamela Genome Core Facility, Institute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA aut NATIONALLICENCE 700 1- Umaña Paula Departments of Psychiatry and Pediatrics, Hospital Nacional de Niños, San Josè, Costa Rica aut NATIONALLICENCE 700 1- Fournier Eduardo Departments of Psychiatry and Pediatrics, Hospital Nacional de Niños, San Josè, Costa Rica aut NATIONALLICENCE 700 1- Murray Sarah Department of Genetics, Scripps Genomic Medicine, La Jolla, CA, USA aut NATIONALLICENCE 700 1- Mathews Carol Department of Psychiatry, University of California, San Francisco, 401 Parnassus Avenue, 94143-0984, San Francisco, CA, USA aut NATIONALLICENCE 773 0- Human Genetics Springer-Verlag 130/6(2011-12-01), 795-805 0340-6717 130:6<795 2011 130 439 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer