title: Exploration of large, rare copy number variants associated with psychiatric and neurodevelopmental disorders in individuals with anorexia nervosa.
abstract: Anorexia nervosa (AN) is a serious and heritable psychiatric disorder. To date, studies of copy number variants (CNVs) have been limited and inconclusive because of small sample sizes. We conducted a case-only genome-wide CNV survey in 1983 female AN cases included in the Genetic Consortium for Anorexia Nervosa. Following stringent quality control procedures, we investigated whether pathogenic CNVs in regions previously implicated in psychiatric and neurodevelopmental disorders were present in AN cases. We observed two instances of the well-established pathogenic CNVs in AN cases. In addition, one case had a deletion in the 13q12 region, overlapping with a deletion reported previously in two AN cases. As a secondary aim, we also examined our sample for CNVs over 1 Mbp in size. Out of the 40 instances of such large CNVs that were not implicated previously for AN or neuropsychiatric phenotypes, two of them contained genes with previous neuropsychiatric associations, and only five of them had no associated reports in public CNV databases. Although ours is the largest study of its kind in AN, larger datasets are needed to comprehensively assess the role of CNVs in the etiology of AN.
authors.affiliation: Department of Psychiatry, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Zeynep
authors.initials: Z
authors.lastname: Yilmaz
authors.affiliation: Department of Genetics, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Jin P
authors.initials: JP
authors.lastname: Szatkiewicz
authors.affiliation: Department of Psychiatry, University of North Carolina, Chapel Hill, NC, USA.|Department of Genetics, University of North Carolina, Chapel Hill, NC, USA.|Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: James J
authors.initials: JJ
authors.lastname: Crowley
authors.affiliation: Department of Genetics, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: NaEshia
authors.initials: N
authors.lastname: Ancalade
authors.affiliation: Department of Neuroscience and Pharmacology, University Medical Center Utrecht, Utrecht, The Netherlands.|Altrecht Eating Disorders Rintveld, Zeist, The Netherlands.
authors.forename: Marek K
authors.initials: MK
authors.lastname: Brandys
authors.affiliation: Altrecht Eating Disorders Rintveld, Zeist, The Netherlands.|Department of Child and Adolescent Psychiatry, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Annemarie
authors.initials: A
authors.lastname: van Elburg
authors.affiliation: Department of Medical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Carolien G F
authors.initials: CGF
authors.lastname: de Kovel
authors.affiliation: Department of Neuroscience and Pharmacology, University Medical Center Utrecht, Utrecht, The Netherlands.|Altrecht Eating Disorders Rintveld, Zeist, The Netherlands.
authors.forename: Roger A H
authors.initials: RAH
authors.lastname: Adan
authors.affiliation: Department of Child and Adolescent Psychiatry, Psychotherapy, and Psychosomatics, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: Anke
authors.initials: A
authors.lastname: Hinney
authors.affiliation: Department of Child and Adolescent Psychiatry, Psychotherapy, and Psychosomatics, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Hebebrand
authors.affiliation: Genetic Causes of Disease Group, Centre for Genomic Regulation, Barcelona, Spain.|Universitat Pompeu Fabra, Barcelona, Spain.|Centro de Investigación Biomédica en Red en Epidemiología y Salud Pública, Barcelona, Spain.
authors.forename: Monica
authors.initials: M
authors.lastname: Gratacos
authors.affiliation: Department of Psychiatry and CIBEROBN, University Hospital of Bellvitge-IDIBELL, Barcelona, Spain.|Department of Clinical Sciences, School of Medicine, University of Barcelona, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Fernandez-Aranda
authors.affiliation: Genetic Causes of Disease Group, Centre for Genomic Regulation, Barcelona, Spain.|Universitat Pompeu Fabra, Barcelona, Spain.|Centro de Investigación Biomédica en Red en Epidemiología y Salud Pública, Barcelona, Spain.
authors.forename: Georgia
authors.initials: G
authors.lastname: Escaramis
authors.affiliation: Universitat Pompeu Fabra, Barcelona, Spain.|Centro de Investigación Biomédica en Red en Epidemiología y Salud Pública, Barcelona, Spain.|ISGLOBAL, Centre for Research in Environmental Epidemiology, Barcelona, Spain.
authors.forename: Juan R
authors.initials: JR
authors.lastname: Gonzalez
authors.affiliation: Genetic Causes of Disease Group, Centre for Genomic Regulation, Barcelona, Spain.|Universitat Pompeu Fabra, Barcelona, Spain.|Centro de Investigación Biomédica en Red en Epidemiología y Salud Pública, Barcelona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Estivill
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, UK.
authors.forename: Eleftheria
authors.initials: E
authors.lastname: Zeggini
authors.affiliation: Department of Psychiatry, University of North Carolina, Chapel Hill, NC, USA.|Department of Genetics, University of North Carolina, Chapel Hill, NC, USA.|Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Patrick F
authors.initials: PF
authors.lastname: Sullivan
authors.affiliation: Department of Psychiatry, University of North Carolina, Chapel Hill, NC, USA.|Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.|Department of Nutrition, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Cynthia M
authors.initials: CM
authors.lastname: Bulik
mesh_terms: D000328:Adult; D000856:Anorexia Nervosa / Q000235:genetics* / Q000523:psychology*; D056915:DNA Copy Number Variations / Q000235:genetics*; D030541:Databases, Genetic; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D055106:Genome-Wide Association Study; D006801:Humans; D065886:Neurodevelopmental Disorders / Q000235:genetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012307:Risk Factors