Polygenic scores differentially predict developmental trajectories of subtypes of social withdrawal in childhood
Geneviève Morneau-Vaillancourt
École de psychologie, Université Laval, Quebec City, QC, Canada
Search for more papers by this authorTill F. M. Andlauer
Department of Neurology, Technical University of Munich, Munich, Germany
Search for more papers by this authorIsabelle Ouellet-Morin
École de criminologie, Université de Montréal, Montreal, QC, Canada
Search for more papers by this authorStéphane Paquin
Department of Psychology, The Pennsylvania State University, State College, PA, USA
Search for more papers by this authorMara R. Brendgen
Département de psychologie, Université du Québec à Montréal, Montreal, QC, Canada
Search for more papers by this authorFrank Vitaro
École de psychoéducation, Université de Montréal, Montreal, QC, Canada
Search for more papers by this authorJean-Philippe Gouin
Department of Psychology, Concordia University, Montreal, QC, Canada
Search for more papers by this authorJean R. Séguin
Département de psychiatrie et d'addictologie, Université de Montréal, Montreal, QC, Canada
Centre de recherche du CHU Sainte-Justine, Montreal, QC Canada
Search for more papers by this authorÉloi Gagnon
École de psychologie, Université Laval, Quebec City, QC, Canada
Search for more papers by this authorRosa Cheesman
Promenta Research Centre, University of Oslo, Oslo, Norway
Search for more papers by this authorNadine Forget-Dubois
École de psychologie, Université Laval, Quebec City, QC, Canada
Search for more papers by this authorGuy A. Rouleau
Institut-hôpital neurologique de Montréal, McGill University, Montreal, QC, Canada
Search for more papers by this authorGustavo Turecki
Douglas Research Centre, McGill University, Montreal, QC, Canada
Search for more papers by this authorRichard E. Tremblay
Départements de pédiatrie et de psychologie, Université de Montréal, Montreal, QC, Canada
Search for more papers by this authorSylvana M. Côté
Département de médecine sociale et préventive, Université de Montréal, Montreal, QC, Canada
Search for more papers by this authorGinette Dionne
École de psychologie, Université Laval, Quebec City, QC, Canada
Search for more papers by this authorCorresponding Author
Michel Boivin
École de psychologie, Université Laval, Quebec City, QC, Canada
Correspondence
Michel Boivin, Université Laval, 2325 Allée des Bibliothèques, Quebec City, QC G1V 0A6, Canada; Email: [email protected]
Search for more papers by this authorGeneviève Morneau-Vaillancourt
École de psychologie, Université Laval, Quebec City, QC, Canada
Search for more papers by this authorTill F. M. Andlauer
Department of Neurology, Technical University of Munich, Munich, Germany
Search for more papers by this authorIsabelle Ouellet-Morin
École de criminologie, Université de Montréal, Montreal, QC, Canada
Search for more papers by this authorStéphane Paquin
Department of Psychology, The Pennsylvania State University, State College, PA, USA
Search for more papers by this authorMara R. Brendgen
Département de psychologie, Université du Québec à Montréal, Montreal, QC, Canada
Search for more papers by this authorFrank Vitaro
École de psychoéducation, Université de Montréal, Montreal, QC, Canada
Search for more papers by this authorJean-Philippe Gouin
Department of Psychology, Concordia University, Montreal, QC, Canada
Search for more papers by this authorJean R. Séguin
Département de psychiatrie et d'addictologie, Université de Montréal, Montreal, QC, Canada
Centre de recherche du CHU Sainte-Justine, Montreal, QC Canada
Search for more papers by this authorÉloi Gagnon
École de psychologie, Université Laval, Quebec City, QC, Canada
Search for more papers by this authorRosa Cheesman
Promenta Research Centre, University of Oslo, Oslo, Norway
Search for more papers by this authorNadine Forget-Dubois
École de psychologie, Université Laval, Quebec City, QC, Canada
Search for more papers by this authorGuy A. Rouleau
Institut-hôpital neurologique de Montréal, McGill University, Montreal, QC, Canada
Search for more papers by this authorGustavo Turecki
Douglas Research Centre, McGill University, Montreal, QC, Canada
Search for more papers by this authorRichard E. Tremblay
Départements de pédiatrie et de psychologie, Université de Montréal, Montreal, QC, Canada
Search for more papers by this authorSylvana M. Côté
Département de médecine sociale et préventive, Université de Montréal, Montreal, QC, Canada
Search for more papers by this authorGinette Dionne
École de psychologie, Université Laval, Quebec City, QC, Canada
Search for more papers by this authorCorresponding Author
Michel Boivin
École de psychologie, Université Laval, Quebec City, QC, Canada
Correspondence
Michel Boivin, Université Laval, 2325 Allée des Bibliothèques, Quebec City, QC G1V 0A6, Canada; Email: [email protected]
Search for more papers by this authorConflict of interest statement: No conflicts declared.
Abstract
Background
Children who consistently withdraw from social situations face increased risk for later socioemotional difficulties. Twin studies indicate that genetic factors substantially account for the persistence of social withdrawal over time. However, the molecular genetic etiology of chronic courses of social wariness and preference for solitude, two dimensions of social withdrawal, remains undocumented. The objectives of the present study were (a) to identify high-risk trajectories for social wariness and preference for solitude in childhood and (b) to examine whether falling on these high-risk trajectories can be predicted by specific polygenic scores for mental health traits and disorders and by a general polygenic predisposition to these traits.
Methods
Teachers evaluated 971 genotyped children at five occasions (age 6 to 12 years) from two prospective longitudinal studies, the Quebec Newborn Twin Study and the Quebec Longitudinal Study of Child Development. Developmental trajectories for social wariness and preference for solitude were identified. We tested whether polygenic scores for attention deficit hyperactivity disorder, autism spectrum disorder, depression, loneliness, and subjective well-being, as well as a general mental health genetic risk score derived across these traits, were associated with the developmental trajectories.
Results
Polygenic scores differentially predicted social wariness and preference for solitude. Only the loneliness polygenic score significantly predicted the high trajectory for social wariness. By contrast, the general mental health genetic risk score factor was associated with the trajectory depicting high-chronic preference for solitude.
Conclusions
Distinct associations were uncovered between the polygenic scores, social wariness, and preference for solitude.
Supporting Information
Filename | Description |
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jcpp13459-sup-0001-Supinfo.docxWord document, 1.4 MB |
Appendix S1. Methods. Table S1. Overview of genome-wide association studies used to calculate polygenic scores. Table S2. Descriptive statistics for social wariness and preference for solitude. Table S3. Results from multinomial regressions using the R3STEP option in Mplus (N = 971). Table S4. Pearson correlations between social wariness and preference for solitude across assessment waves. Table S5. Pearson correlations between polygenic scores. Table S6. Covariates included the multinomial and logistic regressions presented in Table 2. Table S7. Models presented in Table 2 without controlling for the other subtype of social withdrawal. Table S8. Results from the logistic regression predicting the 2-class latent class growth analysis for social wariness. Figure S1. Population substructure (genetic ancestry components) in the Quebec Longitudinal Study of Child Development. Figure S2. Population substructure (genetic ancestry components) in the Quebec Newborn Twin Study. Figure S3. Distribution of social wariness and preference for solitude variables. Figure S4. Latent class growth analysis 2-class model for social wariness (N = 1,058). |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
References
- Achenbach, T.M. (1991). Manual for the child behavior checklist/4-18 and 1991 profile. Department of Psychiatry, Burlington: University of Vermont.
- Allegrini, A.G., Cheesman, R., Rimfeld, K., Selzam, S., Pingault, J., Eley, T.C., & Plomin, R. (2020). The p factor: Genetic analyses support a general dimension of psychopathology in childhood and adolescence. Journal of Child Psychology and Psychiatry, 61, 30–39.
- Anderson, D.K., Maye, M.P., & Lord, C. (2011). Changes in maladaptive behaviors from midchildhood to young adulthood in autism spectrum sisorder. American Journal on Intellectual and Developmental Disabilities, 116, 381–397.
- Andlauer, T.F.M., & Nöthen, M.M. (2020). Polygenic scores for psychiatric disease: From research tool to clinical application. Medizinische Genetik, 32, 39–45.
- Asendorpf, J.B. (1987). Videotape reconstruction of emotions and cognitions related to shyness. Journal of Personality and Social Psychology, 53, 542–549.
- Asparouhov, T., & Muthén, B. (2014). Auxiliary variables in mixture modeling: Three-step approaches using Mplus. Structural Equation Modeling: A Multidisciplinary Journal, 21, 329–341.
- Boivin, M., Brendgen, M., Dionne, G., Ouellet-Morin, I., Dubois, L., Pérusse, D., … & Vitaro, F. (2019). The Quebec Newborn Twin Study at 21. Twin Research and Human Genetics, 22, 475–481.
- Boivin, M., Hymel, S., & Bukowski, W.M. (1995). The roles of social withdrawal, peer rejection, and victimization by peers in predicting loneliness and depressed mood in childhood. Development and Psychopathology, 7, 765–785.
- Bukowski, W.M., Castellanos, M., Vitaro, F., & Brendgen, M. (2015). Socialization and experiences with peers. In J.E. Grusec & P.D. Hastings (Eds.), Handbook of socialization: Theory and research (pp. 228–250). New York: The Guilford Press.
- Buss, K.A. (2011). Which fearful toddlers should we worry about? Context, fear regulation, and anxiety risk. Developmental Psychology, 47, 804–819.
- Chamberlain, B., Kasari, C., & Rotheram-Fuller, E. (2007). Involvement or isolation? The social networks of children with autism in regular classrooms. Journal of Autism and Developmental Disorders, 37, 230–242.
- Chen, X., He, Y., Oliveira, A.M.D., Coco, A.L., Zappulla, C., Kaspar, V., … & DeSouza, A. (2004). Loneliness and social adaptation in Brazilian, Canadian, Chinese and Italian children: A multi-national comparative study. Journal of Child Psychology and Psychiatry, 45, 1373–1384.
- Coplan, R.J., Rose-Krasnor, L., Weeks, M., Kingsbury, A., Kingsbury, M., & Bullock, A. (2013). Alone is a crowd: Social motivations, social withdrawal, and socioemotional functioning in later childhood. Developmental Psychology, 49, 861–875.
- Coplan, R.J., & Weeks, M. (2010). Unsociability and the preference for solitude in childhood. In K.H. Rubin & R.J. Coplan (Eds.), The development of shyness and social withdrawal (pp. 64–83). New York: Guilford Press.
- Day, F.R., Ong, K.K., & Perry, J.R.B. (2018). Elucidating the genetic basis of social interaction and isolation. Nature Communications, 9, 2457.
- Degnan, K.A., Almas, A.N., Henderson, H.A., Hane, A.A., Walker, O.L., & Fox, N.A. (2014). Longitudinal trajectories of social reticence with unfamiliar peers across early childhood. Developmental Psychology, 50, 2311–2323.
- Degnan, K.A., Henderson, H.A., Fox, N.A., & Rubin, K.H. (2008). Predicting social wariness in middle childhood: The moderating roles of child care history, maternal personality and maternal behavior. Social Development, 17, 471–487.
- Demontis, D., Walters, R.K., Martin, J., Mattheisen, M., Als, T.D., Agerbo, E., … & Neale, B.M. (2019). Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder. Nature Genetics, 51, 63–75.
- Fordham, K., & Stevenson-Hinde, J. (1999). Shyness, friendship quality, and adjustment during middle childhood. The . Journal of Child Psychology and Psychiatry and Allied Disciplines, 40, 757–768.
- Ge, T., Chen, C.Y., Ni, Y., Feng, Y.C.A., & Smoller, J.W. (2019). Polygenic prediction via Bayesian regression and continuous shrinkage priors. Nature Communications, 10, 1–10.
- Grove, J., Ripke, S., Als, T.D., Mattheisen, M., Walters, R.K., Won, H., … & Børglum, A.D. (2019). Identification of common genetic risk variants for autism spectrum disorder. Nature Genetics, 51, 431–444.
- Hodgens, J.B., Cole, J., & Boldizar, J. (2000). Peer-based differences among boys with ADHD. Journal of Clinical Child and Adolescent Psychology, 29, 443–452.
- Hoekstra, R.V., Bartels, M., Hudziak, J.J., Van Beijsterveldt, T.C.E.M., & Boomsma, D.I. (2008). Genetic and environmental influences on the stability of withdrawn behavior in children: A longitudinal, multi-informant twin study. Behavior Genetics, 38, 447–461.
- Howard, D.M., Adams, M.J., Clarke, T.-K., Hafferty, J.D., Gibson, J., Shirali, M., … & McIntosh, A.M. (2019). Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions. Nature Neuroscience, 22, 343–352.
- Kiel, E.J., & Buss, K.A. (2014). Dysregulated fear in toddlerhood predicts kindergarten social withdrawal through protective parenting. Infant and Child Development, 313, 304–313.
- Ladd, G.W., Ettekal, I., & Kochenderfer-Ladd, B. (2018). Longitudinal changes in victimized youth’s social anxiety and solitary behavior. Journal of Abnormal Child Psychology, 47, 1211–1223.
- Ladd, G.W., & Profilet, S.M. (1996). The Child Behavior Scale: A teacher-report measure of young children’s aggressive, withdrawn, and prosocial behaviors. Developmental Psychology, 32, 1008–1024.
- Manchia, M., Cullis, J., Turecki, G., Rouleau, G.A., Uher, R., & Alda, M. (2013). The impact of phenotypic and genetic heterogeneity on results of genome wide association studies of complex diseases. PLoS One, 8, e76295.
- Morneau-Vaillancourt, G., Dionne, G., Brendgen, M., Vitaro, F., Feng, B., Henry, J., … & Boivin, M. (2019). The genetic and environmental etiology of shyness through childhood. Behavior Genetics, 49, 376–385.
- Morneau-Vaillancourt, G., Matte-Gagné, C., Cheesman, R., Brendgen, M., Vitaro, F., Tremblay, R., … & Boivin, M. (2021). Social wariness, preference for solitude, and peer difficulties in middle childhood: A longitudinal family-informed study. Developmental Psychology, 57, 410–420.
- Muthen, L.K., & Muthen, B.O. (2017). MPlus user's guide. Los Angeles: Muthen & Muthen.
- Nagin, D.S., & Odgers, C.L. (2010). Group-based trajectory modeling in clinical research. Annual Review of Clinical Psychology, 6, 109–138.
- Okbay, A., Baselmans, B.M.L., De Neve, J.-E., Turley, P., Nivard, M.G., Fontana, M.A., … & Cesarini, D. (2016). Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses. Nature Genetics, 48, 624–633.
- Orri, M., Boivin, M., Chen, C., Ahun, M.N., Geoffroy, M.-C., Ouellet-Morin, I., … & Côté, S.M. (2020). Cohort profile: Quebec Longitudinal Study of Child Development (QLSCD). Social Psychiatry and Psychiatric Epidemiology, 56, 883–894.
- Perkins, D.O., Olde Loohuis, L., Barbee, J., Ford, J., Jeffries, C.D., Addington, J., … & Woods, S.W. (2020). Polygenic risk score contribution to psychosis prediction in a target population of persons at clinical high risk. American Journal of Psychiatry, 177, 155–163.
- Rosenbaum, J.F., Biederman, J., Hirshfeld-Becker, D.R., Kagan, J., Snidman, N., Friedman, D., … & Faraone, S.V. (2000). A controlled study of behavioral inhibition in children of parents with panic disorder and depression. American Journal of Psychiatry, 157, 2002–2010.
- Rubin, K.H., Coplan, R.J., & Bowker, J.C. (2009). Social withdrawal in childhood. Annual Review of Psychology, 60, 141–171.
- Shephard, E., Bedford, R., Milosavljevic, B., Gliga, T., Jones, E.J.H., Pickles, A., … & Charman, T. (2019). Early developmental pathways to childhood symptoms of attention-deficit hyperactivity disorder, anxiety and autism spectrum disorder. Journal of Child Psychology and Psychiatry, 60, 963–974.
- Smith, A.K., Rhee, S.H., Corley, R.P., Friedman, N.P., Hewitt, J.K., & Robinson, J.L. (2012). The magnitude of genetic and environmental influences on parental and observational measures of behavioral inhibition and shyness in toddlerhood. Behavior Genetics, 42, 764–777.
- Steyerberg, E.W., Vickers, A.J., Cook, N.R., Gerds, T., Gonen, M., Obuchowski, N., … & Kattan, M.W. (2010). Assessing the performance of prediction models. Epidemiology, 21, 128–138.
- Tang, A., Van Lieshout, R.J., Lahat, A., Duku, E., Boyle, M.H., Saigal, S., & Schmidt, L.A. (2017). Shyness trajectories across the first four decades predict mental health outcomes. Journal of Abnormal Child Psychology, 45, 1621–1633.
- Wang, J.M., Rubin, K.H., Laursen, B., Booth-LaForce, C., & Rose-Krasnor, L. (2013). Preference-for-solitude and adjustment difficulties in early and late adolescence. Journal of Clinical Child & Adolescent Psychology, 42, 834–842.
- Zdebik, M.A., Boivin, M., Battaglia, M., Tremblay, R.E., Falissard, B., & Côté, S.M. (2019). Childhood multi-trajectories of shyness, anxiety and depression: Associations with adolescent internalizing problems. Journal of Applied Developmental Psychology, 64, 101050.