Evelien Van Assche1,2, Tim Moons1,3, Ozan Cinar4, Wolfgang Viechtbauer4, Albertine J Oldehinkel5,6, Karla Van Leeuwen7, Karine Verschueren8, Hilde Colpin8, Diether Lambrechts9,10, Wim Van den Noortgate11, Luc Goossens8, Stephan Claes1,2, Ruud van Winkel12. 1. GRASP-Research Group, Department of Neuroscience, KU Leuven, Leuven, Belgium. 2. University Psychiatric Center, KU Leuven, Leuven, Belgium. 3. OPZ Geel, Geel, Belgium. 4. Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands. 5. University Medical Center Groningen, Groningen, The Netherlands. 6. Interdisciplinary Center Psychopathology and Emotion Regulation, University of Groningen, Groningen, The Netherlands. 7. Parenting and Special Education Research Unit, Faculty of Psychology and Educational Sciences, KU Leuven, Leuven, Belgium. 8. School Psychology and Child and Adolescent Development Research Unit, Faculty of Psychology and Educational Sciences, KU Leuven, Leuven, Belgium. 9. Vesalius Research Center, VIB, Leuven, Belgium. 10. Laboratory for Translational Genetics, Department of Oncology, KU Leuven, Leuven, Belgium. 11. Department of Methodology of Educational Sciences, Faculty of Psychology and Educational Sciences, KU Leuven, Leuven, Belgium. 12. Department of Neuroscience, Center for Contextual Psychiatry, KU Leuven, Leuven, Belgium.
Abstract
BACKGROUND: Most gene-environment interaction studies (G × E) have focused on single candidate genes. This approach is criticized for its expectations of large effect sizes and occurrence of spurious results. We describe an approach that accounts for the polygenic nature of most psychiatric phenotypes and reduces the risk of false-positive findings. We apply this method focusing on the role of perceived parental support, psychological control, and harsh punishment in depressive symptoms in adolescence. METHODS: Analyses were conducted on 982 adolescents of Caucasian origin (Mage (SD) = 13.78 (.94) years) genotyped for 4,947 SNPs in 263 genes, selected based on a literature survey. The Leuven Adolescent Perceived Parenting Scale (LAPPS) and the Parental Behavior Scale (PBS) were used to assess perceived parental psychological control, harsh punishment, and support. The Center for Epidemiologic Studies Depression Scale (CES-D) was the outcome. We used gene-based testing taking into account linkage disequilibrium to identify genes containing SNPs exhibiting an interaction with environmental factors yielding a p-value per single gene. Significant results at the corrected p-value of p < 1.90 × 10-4 were examined in an independent replication sample of Dutch adolescents (N = 1354). RESULTS: Two genes showed evidence for interaction with perceived support: GABRR1 (p = 4.62 × 10-5 ) and GABRR2 (p = 9.05 × 10-6 ). No genes interacted significantly with psychological control or harsh punishment. Gene-based analysis was unable to confirm the interaction of GABRR1 or GABRR2 with support in the replication sample. However, for GABRR2, but not GABRR1, the correlation of the estimates between the two datasets was significant (r (46) = .32; p = .027) and a gene-based analysis of the combined datasets supported GABRR2 × support interaction (p = 1.63 × 10-4 ). CONCLUSIONS: We present a gene-based method for gene-environment interactions in a polygenic context and show that genes interact differently with particular aspects of parenting. This accentuates the importance of polygenic approaches and the need to accurately assess environmental exposure in G × E.
BACKGROUND: Most gene-environment interaction studies (G × E) have focused on single candidate genes. This approach is criticized for its expectations of large effect sizes and occurrence of spurious results. We describe an approach that accounts for the polygenic nature of most psychiatric phenotypes and reduces the risk of false-positive findings. We apply this method focusing on the role of perceived parental support, psychological control, and harsh punishment in depressive symptoms in adolescence. METHODS: Analyses were conducted on 982 adolescents of Caucasian origin (Mage (SD) = 13.78 (.94) years) genotyped for 4,947 SNPs in 263 genes, selected based on a literature survey. The Leuven Adolescent Perceived Parenting Scale (LAPPS) and the Parental Behavior Scale (PBS) were used to assess perceived parental psychological control, harsh punishment, and support. The Center for Epidemiologic Studies Depression Scale (CES-D) was the outcome. We used gene-based testing taking into account linkage disequilibrium to identify genes containing SNPs exhibiting an interaction with environmental factors yielding a p-value per single gene. Significant results at the corrected p-value of p < 1.90 × 10-4 were examined in an independent replication sample of Dutch adolescents (N = 1354). RESULTS: Two genes showed evidence for interaction with perceived support: GABRR1 (p = 4.62 × 10-5 ) and GABRR2 (p = 9.05 × 10-6 ). No genes interacted significantly with psychological control or harsh punishment. Gene-based analysis was unable to confirm the interaction of GABRR1 or GABRR2 with support in the replication sample. However, for GABRR2, but not GABRR1, the correlation of the estimates between the two datasets was significant (r (46) = .32; p = .027) and a gene-based analysis of the combined datasets supported GABRR2 × support interaction (p = 1.63 × 10-4 ). CONCLUSIONS: We present a gene-based method for gene-environment interactions in a polygenic context and show that genes interact differently with particular aspects of parenting. This accentuates the importance of polygenic approaches and the need to accurately assess environmental exposure in G × E.
Authors: Maaike Verhagen; Karin J H Verweij; Gerine M A Lodder; Luc Goossens; Karine Verschueren; Karla Van Leeuwen; Wim Van den Noortgate; Stephan Claes; Patricia Bijttebier; Evelien Van Assche; Jaqueline M Vink Journal: J Res Adolesc Date: 2019-01-29
Authors: Viktoria Chubar; Karla Van Leeuwen; Patricia Bijttebier; Evelien Van Assche; Guy Bosmans; Wim Van den Noortgate; Ruud van Winkel; Luc Goossens; Stephan Claes Journal: Eur Psychiatry Date: 2020-06-08 Impact factor: 5.361
Authors: Stefanie A Nelemans; Marco Boks; Bochao Lin; Tineke Oldehinkel; Pol van Lier; Susan Branje; Wim Meeus Journal: J Youth Adolesc Date: 2020-11-23
Authors: Stefanie A Nelemans; Evelien van Assche; Patricia Bijttebier; Hilde Colpin; Karla van Leeuwen; Karine Verschueren; Stephan Claes; Wim van den Noortgate; Luc Goossens Journal: J Abnorm Child Psychol Date: 2019-07