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Contribution of common and rare variants to bipolar disorder susceptibility in extended pedigrees from population isolates.
Sul, Jae Hoon; Service, Susan K; Huang, Alden Y; Ramensky, Vasily; Hwang, Sun-Goo; Teshiba, Terri M; Park, YoungJun; Ori, Anil P S; Zhang, Zhongyang; Mullins, Niamh; Olde Loohuis, Loes M; Fears, Scott C; Araya, Carmen; Araya, Xinia; Spesny, Mitzi; Bejarano, Julio; Ramirez, Margarita; Castrillón, Gabriel; Gomez-Makhinson, Juliana; Lopez, Maria C; Montoya, Gabriel; Montoya, Claudia P; Aldana, Ileana; Escobar, Javier I; Ospina-Duque, Jorge; Kremeyer, Barbara; Bedoya, Gabriel; Ruiz-Linares, Andres; Cantor, Rita M; Molina, Julio; Coppola, Giovanni; Ophoff, Roel A; Macaya, Gabriel; Lopez-Jaramillo, Carlos; Reus, Victor; Bearden, Carrie E; Sabatti, Chiara; Freimer, Nelson B.
Afiliación
  • Sul JH; Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
  • Service SK; Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
  • Huang AY; Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University California Los Angeles, Los Angeles, CA, USA.
  • Ramensky V; Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
  • Hwang SG; Bioinformatics Interdepartmental Program, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
  • Teshiba TM; Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
  • Park Y; Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University California Los Angeles, Los Angeles, CA, USA.
  • Ori APS; Federal State Institution "National Medical Research Center for Preventive Medicine" of the Ministry of Healthcare of the Russian Federation. Petroverigskiy lane 10, Moscow, 101990, Russia.
  • Zhang Z; Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
  • Mullins N; Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
  • Olde Loohuis LM; Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University California Los Angeles, Los Angeles, CA, USA.
  • Fears SC; Department of Computer Science, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
  • Araya C; Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University California Los Angeles, Los Angeles, CA, USA.
  • Araya X; Department of Genetics and Genomic Sciences, Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • Spesny M; King's College London, Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, De Crespigny Park, Denmark Hill, London, SE5 8AF, UK.
  • Bejarano J; Pamela Sklar Division of Psychiatric Genomics, Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • Ramirez M; Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University California Los Angeles, Los Angeles, CA, USA.
  • Castrillón G; Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
  • Gomez-Makhinson J; Cell and Molecular Biology Research Center, Universidad de Costa Rica, San Pedro de Montes de Oca, San José, 11501, Costa Rica.
  • Lopez MC; Cell and Molecular Biology Research Center, Universidad de Costa Rica, San Pedro de Montes de Oca, San José, 11501, Costa Rica.
  • Montoya G; Division of Pediatric Pulmonology, Hospital Nacional de Nin ̃os, San Jose, Costa Rica.
  • Montoya CP; Cell and Molecular Biology Research Center, Universidad de Costa Rica, San Pedro de Montes de Oca, San José, 11501, Costa Rica.
  • Aldana I; Cell and Molecular Biology Research Center, Universidad de Costa Rica, San Pedro de Montes de Oca, San José, 11501, Costa Rica.
  • Escobar JI; Instituto de Alta Tecnologia Medica, Medellín, Antioquia, Colombia.
  • Ospina-Duque J; Department of Neuroradiology, Klinikum rechts der Isar, TUM, Munich, Germany.
  • Kremeyer B; Grupo de Investigación en Psiquiatría (Research Group in Psychiatry; GIPSI), Departamento de Psiquiatría Facultad de Medicina, Universidad de Antioquia, Medellín, 050011, Colombia.
  • Bedoya G; Grupo de Investigación en Psiquiatría (Research Group in Psychiatry; GIPSI), Departamento de Psiquiatría Facultad de Medicina, Universidad de Antioquia, Medellín, 050011, Colombia.
  • Ruiz-Linares A; Grupo de Investigación en Psiquiatría (Research Group in Psychiatry; GIPSI), Departamento de Psiquiatría Facultad de Medicina, Universidad de Antioquia, Medellín, 050011, Colombia.
  • Cantor RM; Grupo de Investigación en Psiquiatría (Research Group in Psychiatry; GIPSI), Departamento de Psiquiatría Facultad de Medicina, Universidad de Antioquia, Medellín, 050011, Colombia.
  • Molina J; Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
  • Coppola G; Department of Psychiatry and Family Medicine, Rutgers-Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ, 08901, USA.
  • Ophoff RA; Grupo de Investigación en Psiquiatría (Research Group in Psychiatry; GIPSI), Departamento de Psiquiatría Facultad de Medicina, Universidad de Antioquia, Medellín, 050011, Colombia.
  • Macaya G; Department of Genetics, Evolution and Environment, University College London, London, WC1E 6BT, UK.
  • Lopez-Jaramillo C; Laboratory of Molecular Genetics, Institute of Biology, University of Antioquia, Medellín, 050010, Colombia.
  • Reus V; Ministry of Education Key Laboratory of Contemporary Anthropology and Collaborative Innovation Center of Genetics and Development, Fudan University, Shanghai, 200438, China.
  • Bearden CE; Aix Marseille Univ, CNRS, EFS, ADES, Marseille, France.
  • Sabatti C; Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
  • Freimer NB; Department of Human Genetics, University of California Los Angeles, Los Angeles, CA, 90095, USA.
Transl Psychiatry ; 10(1): 74, 2020 02 24.
Article en En | MEDLINE | ID: mdl-32094344
Current evidence from case/control studies indicates that genetic risk for psychiatric disorders derives primarily from numerous common variants, each with a small phenotypic impact. The literature describing apparent segregation of bipolar disorder (BP) in numerous multigenerational pedigrees suggests that, in such families, large-effect inherited variants might play a greater role. To identify roles of rare and common variants on BP, we conducted genetic analyses in 26 Colombia and Costa Rica pedigrees ascertained for bipolar disorder 1 (BP1), the most severe and heritable form of BP. In these pedigrees, we performed microarray SNP genotyping of 838 individuals and high-coverage whole-genome sequencing of 449 individuals. We compared polygenic risk scores (PRS), estimated using the latest BP1 genome-wide association study (GWAS) summary statistics, between BP1 individuals and related controls. We also evaluated whether BP1 individuals had a higher burden of rare deleterious single-nucleotide variants (SNVs) and rare copy number variants (CNVs) in a set of genes related to BP1. We found that compared with unaffected relatives, BP1 individuals had higher PRS estimated from BP1 GWAS statistics (P = 0.001 ~ 0.007) and displayed modest increase in burdens of rare deleterious SNVs (P = 0.047) and rare CNVs (P = 0.002 ~ 0.033) in genes related to BP1. We did not observe rare variants segregating in the pedigrees. These results suggest that small-to-moderate effect rare and common variants are more likely to contribute to BP1 risk in these extended pedigrees than a few large-effect rare variants.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Trastorno Bipolar Tipo de estudio: Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Transl Psychiatry Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Trastorno Bipolar Tipo de estudio: Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Transl Psychiatry Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos