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Genome-wide Association Meta-analysis of Childhood and Adolescent Internalizing Symptoms.
Jami, Eshim S; Hammerschlag, Anke R; Ip, Hill F; Allegrini, Andrea G; Benyamin, Beben; Border, Richard; Diemer, Elizabeth W; Jiang, Chang; Karhunen, Ville; Lu, Yi; Lu, Qing; Mallard, Travis T; Mishra, Pashupati P; Nolte, Ilja M; Palviainen, Teemu; Peterson, Roseann E; Sallis, Hannah M; Shabalin, Andrey A; Tate, Ashley E; Thiering, Elisabeth; Vilor-Tejedor, Natàlia; Wang, Carol; Zhou, Ang; Adkins, Daniel E; Alemany, Silvia; Ask, Helga; Chen, Qi; Corley, Robin P; Ehli, Erik A; Evans, Luke M; Havdahl, Alexandra; Hagenbeek, Fiona A; Hakulinen, Christian; Henders, Anjali K; Hottenga, Jouke Jan; Korhonen, Tellervo; Mamun, Abdullah; Marrington, Shelby; Neumann, Alexander; Rimfeld, Kaili; Rivadeneira, Fernando; Silberg, Judy L; van Beijsterveldt, Catharina E; Vuoksimaa, Eero; Whipp, Alyce M; Tong, Xiaoran; Andreassen, Ole A; Boomsma, Dorret I; Brown, Sandra A; Burt, S Alexandra.
Afiliação
  • Jami ES; Vrije Universiteit Amsterdam, Amsterdam, the Netherlands; University College London, London, United Kingdom. Electronic address: e.shahid@ucl.ac.uk.
  • Hammerschlag AR; Vrije Universiteit Amsterdam, Amsterdam, the Netherlands; Amsterdam Public Health Research Institute, Amsterdam, the Netherlands; Child Health Research Centre, University of Queensland, Brisbane, Australia.
  • Ip HF; Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
  • Allegrini AG; University College London, London, United Kingdom; Social, Genetic and Developmental Psychiatry Centre, King's College London, London, United Kingdom.
  • Benyamin B; University of South Australia, Adelaide, Australia; South Australian Health and Medical Research Institute, Adelaide, Australia.
  • Border R; Institute for Behavioral Genetics, University of Colorado Boulder.
  • Diemer EW; Erasmus University Medical Center, Rotterdam, the Netherlands; Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
  • Jiang C; Michigan State University, East Lansing; University of Florida, Gainesville.
  • Karhunen V; Imperial College London, United Kingdom.
  • Lu Y; Karolinska Institutet, Stockholm, Sweden.
  • Lu Q; Michigan State University, East Lansing.
  • Mallard TT; University of Texas, Austin.
  • Mishra PP; Tampere University, Tampere, Finland, and Fimlab Laboratories, Tampere, Finland.
  • Nolte IM; University of Groningen, University Medical Center Groningen, the Netherlands.
  • Palviainen T; Institute for Molecular Medicine Finland - FIMM, University of Helsinki, Finland.
  • Peterson RE; Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond.
  • Sallis HM; School of Psychological Science, University of Bristol, United Kingdom, and Medical Research Council (MRC) Integrative Epidemiology Unit, University of Bristol, United Kingdom; Centre for Academic Mental Health, Population Health Sciences, University of Bristol, United Kingdom.
  • Shabalin AA; University of Utah, Salt Lake City.
  • Tate AE; Karolinska Institutet, Stockholm, Sweden.
  • Thiering E; Institute of Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany; Ludwig-Maximilians-Universität, Munich, Germany.
  • Vilor-Tejedor N; Erasmus University Medical Center, Rotterdam, the Netherlands; Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain; BarcelonaBeta Brain Research Center, (BBRC) Pasqual Maragall Foundation, Barcelona, Spain; Universitat Pompeu Fabra (UPF), Barcelon
  • Wang C; School of Medicine and Public Health, University of Newcastle, Australia.
  • Zhou A; University of South Australia, Adelaide, Australia.
  • Adkins DE; University of Utah, Salt Lake City.
  • Alemany S; Universitat Pompeu Fabra (UPF), Barcelona, Spain; SGlobal, Barcelona Institute of Global Health, Barcelona, Spain; and CIBER Epidemiología y Salud Pública (CIBERESP), Spain.
  • Ask H; Norwegian Institute of Public Health, Oslo, Norway.
  • Chen Q; Karolinska Institutet, Stockholm, Sweden.
  • Corley RP; Institute for Behavioral Genetics, University of Colorado Boulder.
  • Ehli EA; Avera Institute for Human Genetics, Avera McKennan Hospital & University Health Center, Sioux Falls, South Dakota.
  • Evans LM; Institute for Behavioral Genetics, University of Colorado Boulder.
  • Havdahl A; Norwegian Institute of Public Health, Oslo, Norway.
  • Hagenbeek FA; Vrije Universiteit Amsterdam, Amsterdam, the Netherlands; Amsterdam Public Health Research Institute, Amsterdam, the Netherlands.
  • Hakulinen C; University of Helsinki, Helsinki, Finland.
  • Henders AK; Institute for Molecular Biosciences, University of Queensland, Brisbane, Australia.
  • Hottenga JJ; Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
  • Korhonen T; Institute for Molecular Medicine Finland - FIMM, University of Helsinki, Finland.
  • Mamun A; Institute for Social Science Research, University of Queensland, Brisbane, Australia.
  • Marrington S; School of Public Health, University of Queensland, Brisbane, Australia.
  • Neumann A; Erasmus University Medical Center, Rotterdam, the Netherlands; Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Canada.
  • Rimfeld K; Social, Genetic and Developmental Psychiatry Centre, King's College London, London, United Kingdom.
  • Rivadeneira F; Erasmus University Medical Center, Rotterdam, the Netherlands.
  • Silberg JL; Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond.
  • van Beijsterveldt CE; Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
  • Vuoksimaa E; Institute for Molecular Medicine Finland - FIMM, University of Helsinki, Finland.
  • Whipp AM; Institute for Molecular Medicine Finland - FIMM, University of Helsinki, Finland.
  • Tong X; Michigan State University, East Lansing; University of Florida, Gainesville.
  • Andreassen OA; NORMENT Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; and Oslo University Hospital, Norway.
  • Boomsma DI; Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
  • Brown SA; University of California San Diego, La Jolla.
  • Burt SA; Michigan State University, East Lansing.
J Am Acad Child Adolesc Psychiatry ; 61(7): 934-945, 2022 07.
Article em En | MEDLINE | ID: mdl-35378236
ABSTRACT

OBJECTIVE:

To investigate the genetic architecture of internalizing symptoms in childhood and adolescence.

METHOD:

In 22 cohorts, multiple univariate genome-wide association studies (GWASs) were performed using repeated assessments of internalizing symptoms, in a total of 64,561 children and adolescents between 3 and 18 years of age. Results were aggregated in meta-analyses that accounted for sample overlap, first using all available data, and then using subsets of measurements grouped by rater, age, and instrument.

RESULTS:

The meta-analysis of overall internalizing symptoms (INToverall) detected no genome-wide significant hits and showed low single nucleotide polymorphism (SNP) heritability (1.66%, 95% CI = 0.84-2.48%, neffective = 132,260). Stratified analyses indicated rater-based heterogeneity in genetic effects, with self-reported internalizing symptoms showing the highest heritability (5.63%, 95% CI = 3.08%-8.18%). The contribution of additive genetic effects on internalizing symptoms appeared to be stable over age, with overlapping estimates of SNP heritability from early childhood to adolescence. Genetic correlations were observed with adult anxiety, depression, and the well-being spectrum (|rg| > 0.70), as well as with insomnia, loneliness, attention-deficit/hyperactivity disorder, autism, and childhood aggression (range |rg| = 0.42-0.60), whereas there were no robust associations with schizophrenia, bipolar disorder, obsessive-compulsive disorder, or anorexia nervosa.

CONCLUSION:

Genetic correlations indicate that childhood and adolescent internalizing symptoms share substantial genetic vulnerabilities with adult internalizing disorders and other childhood psychiatric traits, which could partially explain both the persistence of internalizing symptoms over time and the high comorbidity among childhood psychiatric traits. Reducing phenotypic heterogeneity in childhood samples will be key in paving the way to future GWAS success.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Transtorno do Deficit de Atenção com Hiperatividade / Transtorno Autístico / Estudo de Associação Genômica Ampla / Distúrbios do Início e da Manutenção do Sono Idioma: En Ano de publicação: 2022 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Transtorno do Deficit de Atenção com Hiperatividade / Transtorno Autístico / Estudo de Associação Genômica Ampla / Distúrbios do Início e da Manutenção do Sono Idioma: En Ano de publicação: 2022 Tipo de documento: Article