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1. Genome-wide association meta-analysis of childhood and adolescent internalizing symptoms

Author

Jami, E. S. (Eshim S.), Hammerschlag, A. R. (Anke R.), Ip, H. F. (Hill F.), Allegrini, A. G. (Andrea G.), Benyamin, B. (Beben), Border, R. (Richard), Diemer, E. W. (Elizabeth W.), Jiang, C. (Chang), Karhunen, V. (Ville), Lu, Y. (Yi), Lu, Q. (Qing), Mallard, T. T. (Travis T.), Mishra, P. P. (Pashupati P.), Nolte, I. M. (Ilja M.), Palviainen, T. (Teemu), Peterson, R. E. (Roseann E.), Sallis, H. M. (Hannah M.), Shabalin, A. A. (Andrey A.), Tate, A. E. (Ashley E.), Thiering, E. (Elisabeth), Vilor-Tejedor, N. (Natalia), Wang, C. (Carol), Zhou, A. (Ang), Adkins, D. E. (Daniel E.), Alemany, S. (Silvia), Ask, H. (Helga), Chen, Q. (Qi), Corley, R. P. (Robin P.), Ehli, E. A. (Erik A.), Evans, L. M. (Luke M.), Havdahl, A. (Alexandra), Hagenbeek, F. A. (Fiona A.), Hakulinen, C. (Christian), Henders, A. K. (Anjali K.), Hottenga, J. J. (Jouke Jan), Korhonen, T. (Tellervo), Mamun, A. (Abdullah), Marrington, S. (Shelby), Neumann, A. (Alexander), Rimfeld, K. (Kaili), Rivadeneira, F. (Fernando), Silberg, J. L. (Judy L.), van Beijsterveldt, C. E. (Catharina E.), Vuoksimaa, E. (Eero), Whipp, A. M. (Alyce M.), Tong, X. (Xiaoran), Andreassen, O. A. (Ole A.), Boomsma, D. I. (Dorret, I), Brown, S. A. (Sandra A.), Burt, S. A. (S. Alexandra), Copeland, W. (William), Dick, D. M. (Danielle M.), Harden, K. P. (K. Paige), Harris, K. M. (Kathleen Mullan), Hartman, C. A. (Catharina A.), Heinrich, J. (Joachim), Hewitt, J. K. (John K.), Hopfer, C. (Christian), Hypponen, E. (Elina), Järvelin, M.-R. (Marjo-Riitta), Kaprio, J. (Jaakko), Keltikangas-Jarvinen, L. (Liisa), Klump, K. L. (Kelly L.), Krauter, K. (Kenneth), Kuja-Halkola, R. (Ralf), Larsson, H. (Henrik), Lehtimaki, T. (Terho), Lichtenstein, P. (Paul), Lundstrom, S. (Sebastian), Maes, H. H. (Hermine H.), Magnus, P. (Per), Munafo, M. R. (Marcus R.), Najman, J. M. (Jake M.), Njolstad, P. R. (Pal R.), Oldehinkel, A. J. (Albertine J.), Pennell, C. E. (Craig E.), Plomin, R. (Robert), Reichborn-Kjennerud, T. (Ted), Reynolds, C. (Chandra), Rose, R. J. (Richard J.), Smolen, A. (Andrew), Snieder, H. (Harold), Stallings, M. (Michael), Standl, M. (Marie), Sunyer, J. (Jordi), Tiemeier, H. (Henning), Wadsworth, S. J. (Sally J.), Wall, T. L. (Tamara L.), Whitehouse, A. J. (Andrew J. O.), Williams, G. M. (Gail M.), Ystrom, E. (Eivind), Nivard, M. G. (Michel G.), Bartels, M. (Meike), Middeldorp, C. M. (Christel M.), Jami, E. S. (Eshim S.), Hammerschlag, A. R. (Anke R.), Ip, H. F. (Hill F.), Allegrini, A. G. (Andrea G.), Benyamin, B. (Beben), Border, R. (Richard), Diemer, E. W. (Elizabeth W.), Jiang, C. (Chang), Karhunen, V. (Ville), Lu, Y. (Yi), Lu, Q. (Qing), Mallard, T. T. (Travis T.), Mishra, P. P. (Pashupati P.), Nolte, I. M. (Ilja M.), Palviainen, T. (Teemu), Peterson, R. E. (Roseann E.), Sallis, H. M. (Hannah M.), Shabalin, A. A. (Andrey A.), Tate, A. E. (Ashley E.), Thiering, E. (Elisabeth), Vilor-Tejedor, N. (Natalia), Wang, C. (Carol), Zhou, A. (Ang), Adkins, D. E. (Daniel E.), Alemany, S. (Silvia), Ask, H. (Helga), Chen, Q. (Qi), Corley, R. P. (Robin P.), Ehli, E. A. (Erik A.), Evans, L. M. (Luke M.), Havdahl, A. (Alexandra), Hagenbeek, F. A. (Fiona A.), Hakulinen, C. (Christian), Henders, A. K. (Anjali K.), Hottenga, J. J. (Jouke Jan), Korhonen, T. (Tellervo), Mamun, A. (Abdullah), Marrington, S. (Shelby), Neumann, A. (Alexander), Rimfeld, K. (Kaili), Rivadeneira, F. (Fernando), Silberg, J. L. (Judy L.), van Beijsterveldt, C. E. (Catharina E.), Vuoksimaa, E. (Eero), Whipp, A. M. (Alyce M.), Tong, X. (Xiaoran), Andreassen, O. A. (Ole A.), Boomsma, D. I. (Dorret, I), Brown, S. A. (Sandra A.), Burt, S. A. (S. Alexandra), Copeland, W. (William), Dick, D. M. (Danielle M.), Harden, K. P. (K. Paige), Harris, K. M. (Kathleen Mullan), Hartman, C. A. (Catharina A.), Heinrich, J. (Joachim), Hewitt, J. K. (John K.), Hopfer, C. (Christian), Hypponen, E. (Elina), Järvelin, M.-R. (Marjo-Riitta), Kaprio, J. (Jaakko), Keltikangas-Jarvinen, L. (Liisa), Klump, K. L. (Kelly L.), Krauter, K. (Kenneth), Kuja-Halkola, R. (Ralf), Larsson, H. (Henrik), Lehtimaki, T. (Terho), Lichtenstein, P. (Paul), Lundstrom, S. (Sebastian), Maes, H. H. (Hermine H.), Magnus, P. (Per), Munafo, M. R. (Marcus R.), Najman, J. M. (Jake M.), Njolstad, P. R. (Pal R.), Oldehinkel, A. J. (Albertine J.), Pennell, C. E. (Craig E.), Plomin, R. (Robert), Reichborn-Kjennerud, T. (Ted), Reynolds, C. (Chandra), Rose, R. J. (Richard J.), Smolen, A. (Andrew), Snieder, H. (Harold), Stallings, M. (Michael), Standl, M. (Marie), Sunyer, J. (Jordi), Tiemeier, H. (Henning), Wadsworth, S. J. (Sally J.), Wall, T. L. (Tamara L.), Whitehouse, A. J. (Andrew J. O.), Williams, G. M. (Gail M.), Ystrom, E. (Eivind), Nivard, M. G. (Michel G.), Bartels, M. (Meike), and Middeldorp, C. M. (Christel M.)

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.

Published
2022

2. Overview of CAPICE—childhood and adolescence psychopathology:unravelling the complex etiology by a large interdisciplinary collaboration in Europe—an EU Marie Skłodowska‑Curie International Training Network

Author

Rajula, H. S. (Hema Sekhar Reddy), Manchia, M. (Mirko), Agarwal, K. (Kratika), Akingbuwa, W. A. (Wonuola A.), Allegrini, A. G. (Andrea G.), Diemer, E. (Elizabeth), Doering, S. (Sabrina), Haan, E. (Elis), Jami, E. S. (Eshim S.), Karhunen, V. (Ville), Leone, M. (Marica), Schellhas, L. (Laura), Thompson, A. (Ashley), van den Berg, S. M. (Stéphanie M.), Bergen, S. E. (Sarah E.), Kuja-Halkola, R. (Ralf), Hammerschlag, A. R. (Anke R.), Järvelin, M. R. (Marjo Riitta), Leval, A. (Amy), Lichtenstein, P. (Paul), Lundstrom, S. (Sebastian), Mauri, M. (Matteo), Munafò, M. R. (Marcus R.), Myers, D. (David), Plomin, R. (Robert), Rimfeld, K. (Kaili), Tiemeier, H. (Henning), Ystrom, E. (Eivind), Fanos, V. (Vassilios), Bartels, M. (Meike), and Middeldorp, C. M. (Christel M.)

Subjects
Childhood and adolescence psychopathology, Depression, Psychiatric genetics, Attention deficit hyperactivity disorder (ADHD), Anxiety
Abstract

The Roadmap for Mental Health and Wellbeing Research in Europe (ROAMER) identified child and adolescent mental illness as a priority area for research. CAPICE (Childhood and Adolescence Psychopathology: unravelling the complex etiology by a large Interdisciplinary Collaboration in Europe) is a European Union (EU) funded training network aimed at investigating the causes of individual differences in common childhood and adolescent psychopathology, especially depression, anxiety, and attention deficit hyperactivity disorder. CAPICE brings together eight birth and childhood cohorts as well as other cohorts from the EArly Genetics and Life course Epidemiology (EAGLE) consortium, including twin cohorts, with unique longitudinal data on environmental exposures and mental health problems, and genetic data on participants. Here we describe the objectives, summarize the methodological approaches and initial results, and present the dissemination strategy of the CAPICE network. Besides identifying genetic and epigenetic variants associated with these phenotypes, analyses have been performed to shed light on the role of genetic factors and the interplay with the environment in influencing the persistence of symptoms across the lifespan. Data harmonization and building an advanced data catalogue are also part of the work plan. Findings will be disseminated to non-academic parties, in close collaboration with the Global Alliance of Mental Illness Advocacy Networks-Europe (GAMIAN-Europe).

Published
2021

3. Genetic associations between childhood psychopathology and adult depression and associated traits in 42 998 individuals:a meta-analysis

Author

Akingbuwa, W. A. (Wonuola A.), Hammerschlag, A. R. (Anke R.), Jami, E. S. (Eshim S.), Allegrini, A. G. (Andrea G.), Karhunen, V. (Ville), Sallis, H. (Hannah), Ask, H. (Helga), Askeland, R. B. (Ragna B.), Baselmans, B. (Bart), Diemer, E. (Elizabeth), Hagenbeek, F. A. (Fiona A.), Havdahl, A. (Alexandra), Hottenga, J.-J. (Jouke-Jan), Mbarek, H. (Hamdi), Rivadeneira, F. (Fernando), Tesli, M. (Martin), van Beijsterveldt, C. (Catharina), Breen, G. (Gerome), Lewis, C. M. (Cathryn M.), Thapar, A. (Anita), Boomsma, D. I. (Dorret I.), Kuja-Halkola, R. (Ralf), Reichborn-Kjennerud, T. (Ted), Magnus, P. (Per), Rimfeld, K. (Kaili), Ystrom, E. (Eivind), Järvelin, M.-R. (Marjo-Riitta), Lichtenstein, P. (Paul), Lundstrom, S. (Sebastian), Munafo, M. R. (Marcus R.), Plomin, R. (Robert), Tiemeier, H. (Henning), Nivard, M. G. (Michel G.), Bartels, M. (Meike), Middeldorp, C. M. (Christel M.), Akingbuwa, W. A. (Wonuola A.), Hammerschlag, A. R. (Anke R.), Jami, E. S. (Eshim S.), Allegrini, A. G. (Andrea G.), Karhunen, V. (Ville), Sallis, H. (Hannah), Ask, H. (Helga), Askeland, R. B. (Ragna B.), Baselmans, B. (Bart), Diemer, E. (Elizabeth), Hagenbeek, F. A. (Fiona A.), Havdahl, A. (Alexandra), Hottenga, J.-J. (Jouke-Jan), Mbarek, H. (Hamdi), Rivadeneira, F. (Fernando), Tesli, M. (Martin), van Beijsterveldt, C. (Catharina), Breen, G. (Gerome), Lewis, C. M. (Cathryn M.), Thapar, A. (Anita), Boomsma, D. I. (Dorret I.), Kuja-Halkola, R. (Ralf), Reichborn-Kjennerud, T. (Ted), Magnus, P. (Per), Rimfeld, K. (Kaili), Ystrom, E. (Eivind), Järvelin, M.-R. (Marjo-Riitta), Lichtenstein, P. (Paul), Lundstrom, S. (Sebastian), Munafo, M. R. (Marcus R.), Plomin, R. (Robert), Tiemeier, H. (Henning), Nivard, M. G. (Michel G.), Bartels, M. (Meike), and Middeldorp, C. M. (Christel M.)

Abstract

Importance: Adult mood disorders are often preceded by behavioral and emotional problems in childhood. It is yet unclear what explains the associations between childhood psychopathology and adult traits. Objective: To investigate whether genetic risk for adult mood disorders and associated traits is associated with childhood disorders. Design, Setting, and Participants: This meta-analysis examined data from 7 ongoing longitudinal birth and childhood cohorts from the UK, the Netherlands, Sweden, Norway, and Finland. Starting points of data collection ranged from July 1985 to April 2002. Participants were repeatedly assessed for childhood psychopathology from ages 6 to 17 years. Data analysis occurred from September 2017 to May 2019. Exposures: Individual polygenic scores (PGS) were constructed in children based on genome-wide association studies of adult major depression, bipolar disorder, subjective well-being, neuroticism, insomnia, educational attainment, and body mass index (BMI). Main Outcomes and Measures: Regression meta-analyses were used to test associations between PGS and attention-deficit/hyperactivity disorder (ADHD) symptoms and internalizing and social problems measured repeatedly across childhood and adolescence and whether these associations depended on childhood phenotype, age, and rater. Results: The sample included 42 998 participants aged 6 to 17 years. Male participants varied from 43.0% (1040 of 2417 participants) to 53.1% (2434 of 4583 participants) by age and across all cohorts. The PGS of adult major depression, neuroticism, BMI, and insomnia were positively associated with childhood psychopathology (β estimate range, 0.023–0.042 [95% CI, 0.017–0.049]), while associations with PGS of subjective well-being and educational attainment were negative (β, −0.026 to −0.046 [95% CI, −0.020 to −0.057]). There was no moderation of age, type of childhood phenotype, or rater with the associations. The exceptions were stronger associations betwe

Published
2020

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