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DOI 10.1016/j.jaac.2021.11.035

Медицинская библиотека · Journal of the American Academy of Child and Adolescent Psychiatry · 2022

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, Copeland William, Dick Danielle M, Harden K Paige, Harris Kathleen Mullan, Hartman Catharina A, Heinrich Joachim, Hewitt John K, Hopfer Christian, Hypponen Elina, Jarvelin Marjo-Riitta, Kaprio Jaakko, Keltikangas-Järvinen Liisa, Klump Kelly L, Krauter Kenneth, Kuja-Halkola Ralf, Larsson Henrik, Lehtimäki Terho, Lichtenstein Paul, Lundström Sebastian, Maes Hermine H, Magnus Per, Munafò Marcus R, Najman Jake M, Njølstad Pål R, Oldehinkel Albertine J, Pennell Craig E, Plomin Robert, Reichborn-Kjennerud Ted, Reynolds Chandra, Rose Richard J, Smolen Andrew, Snieder Harold, Stallings Michael, Standl Marie, Sunyer Jordi, Tiemeier Henning, Wadsworth Sally J, Wall Tamara L, Whitehouse Andrew J O, Williams Gail M, Ystrøm Eivind, Nivard Michel G, Bartels Meike, Middeldorp Christel M

СтатьяМетаанализПоддержка исследования: вне правительства СШАПеревод в очереди

Аннотация

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.

Для цитирования: 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, Copeland William, Dick Danielle M, Harden K Paige, Harris Kathleen Mullan, Hartman Catharina A, Heinrich Joachim, Hewitt John K, Hopfer Christian, Hypponen Elina, Jarvelin Marjo-Riitta, Kaprio Jaakko, Keltikangas-Järvinen Liisa, Klump Kelly L, Krauter Kenneth, Kuja-Halkola Ralf, Larsson Henrik, Lehtimäki Terho, Lichtenstein Paul, Lundström Sebastian, Maes Hermine H, Magnus Per, Munafò Marcus R, Najman Jake M, Njølstad Pål R, Oldehinkel Albertine J, Pennell Craig E, Plomin Robert, Reichborn-Kjennerud Ted, Reynolds Chandra, Rose Richard J, Smolen Andrew, Snieder Harold, Stallings Michael, Standl Marie, Sunyer Jordi, Tiemeier Henning, Wadsworth Sally J, Wall Tamara L, Whitehouse Andrew J O, Williams Gail M, Ystrøm Eivind, Nivard Michel G, Bartels Meike, Middeldorp Christel M. Genome-wide Association Meta-analysis of Childhood and Adolescent Internalizing Symptoms.. Journal of the American Academy of Child and Adolescent Psychiatry. 2022. DOI: 10.1016/j.jaac.2021.11.035.

Предметные рубрики MeSH

AdolescentAdultAggressionAnxietyAttention Deficit Disorder with HyperactivityAutistic DisorderBipolar DisorderChildChild, PreschoolDepressionGenome-Wide Association StudyHumansLonelinessPolymorphism, Single NucleotideSchizophreniaSleep Initiation and Maintenance Disorders
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