Citation
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, et al. (2022). Genome-Wide Association Meta-Analysis of Childhood and Adolescent Internalizing Symptoms. Journal of the American Academy of Child & Adolescent Psychiatry, 61(7), 934-945.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 (INT(overall)) detected no genome-wide significant hits and showed low single nucleotide polymorphism (SNP) heritability (1.66%, 95% CI = 0.84-2.48%, n(effective) = 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 (|r(g)| > 0.70), as well as with insomnia, loneliness, attention-deficit/hyperactivity disorder, autism, and childhood aggression (range |r(g)| = 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.
URL
http://dx.doi.org/10.1016/j.jaac.2021.11.035Reference Type
Journal ArticleYear Published
2022Journal Title
Journal of the American Academy of Child & Adolescent PsychiatryAuthor(s)
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 A.
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. M.
Vuoksimaa, Eero
Whipp, Alyce M.
Tong, Xiaoran
Andreassen, Ole A.
Boomsma, Dorret I.
Brown, Sandra A.
Burt, S. Alexandra
Copeland, William E.
Dick, Danielle M.
Harden, K. Paige
Harris, Kathleen Mullan
Hartman, Catharina A.
Heinrich, Joachim
Hewitt, John K.
Hopfer, Christian J.
Hypponen, Elina
Jarvelin, Marjo-Riitta
Kaprio, Jaakko
Keltikangas-Järvinen, Liisa
Klump, Kelly L.
Krauter, Kenneth S.
Kuja-Halkola, Ralf
Larsson, Henrik
Lehtimäki, Terho
Lichtenstein, Paul
Lundström, Sebastian
Maes, Hermine H.
Magnus, Per M.
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 C.
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.