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