Gene‐based interaction analysis shows GABA ergic genes interacting with parenting in adolescent depressive symptoms
Open accessAbstract
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 ( M age ( SD ) = 13.78 (.94) years) genotyped for 4,947 SNP s 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 SNP s 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: GABRR 1 ( p = 4.62 × 10 −5 ) and GABRR 2 ( 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 GABRR 1 or GABRR 2 with support in the replication sample. However, for GABRR 2 , but not GABRR 1 , 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 GABRR 2 × 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.
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Adolescence is a time of vulnerability.
“Adolescence is a time of vulnerability [111,480].”
From Biological, Psychological, and Social Determinants of Depression: A Review of Recent Literature (2021) · cites this paper as [480]
Stress interacts with 5-HTTLPR in relation to depression.
“another reported an interaction between stress and 5-HTTLPR in relation to depression [480].”
From Biological, Psychological, and Social Determinants of Depression: A Review of Recent Literature (2021) · cites this paper as [480]
Perceived parental support interacts with genes GABRR1 and GABRR2 and is associated with depressive symptoms in adolescence.
“Perceived parental support has been found to interact with genes (GABRR1, GABRR2), and this appears to be associated with depressive symptoms in adolescence [480].”
From Biological, Psychological, and Social Determinants of Depression: A Review of Recent Literature (2021) · cites this paper as [480]
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- Authors
- Van Assche, E., Moons, T., Cinar, O., Viechtbauer, W., Oldehinkel, A. J., Van Leeuwen, K., Verschueren, K., Colpin, H., Lambrechts, D., Van den Noortgate, W., Goossens, L., Claes, S., & van Winkel, R.
- Affiliations
- GRASP‐Research Group Department of Neuroscience KU Leuven Leuven Belgium
- KU Leuven (BE)
- Maastricht University (NL)
- University Medical Center Groningen (NL)
- Parenting and Special Education Research Unit Faculty of Psychology and Educational Sciences KU Leuven Leuven Belgium
- Department of Methodology of Educational Sciences Faculty of Psychology and Educational Sciences KU Leuven Leuven Belgium
- Department of Neuroscience Center for Contextual Psychiatry KU Leuven Leuven Belgium
- ORCID
- Venue
- Journal of Child Psychology and Psychiatry
- Publisher
- Wiley
- Published
- 2017-06-28
- Volume
- 58
- Issue
- 12
- Pages
- 1301-1309
- ISSN
- 0021-9630 (ISSN-L)
- 1469-7610
- OpenAlex
- W2728267529
- Cited by
- 19
- References
- 57
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 1 · 2022: 6 · 2021: 2 · 2020: 3 · 2019: 3 · 2018: 1 · 2017: 1
- FWCI
- 1.45
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Child Psychology and Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (publishedVersion, other-oa)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion, other-oa)
- Lirias (submittedVersion, other-oa)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
- Research Publications (Maastricht University) (submittedVersion, other-oa)
- Funders
- KU Leuven Research Fund (GOA/12/009)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Social Sciences › Psychology › Clinical Psychology › Child and Adolescent Psychosocial and Emotional Development
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- gene-environment interaction, perceived parental support, psychological control, harsh punishment, parenting, adolescent depressive symptoms, linkage disequilibrium, replication
- MeSH terms
- Adolescent, Belgium, Child, Depression, Female, Humans, Male, Parent-Child Relations, Punishment, Receptors, GABA-A, Social Support, Parenting, Polymorphism, Single Nucleotide, Gene-Environment Interaction
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