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Gene‐based interaction analysis shows GABA ergic genes interacting with parenting in adolescent depressive symptoms
Author(s) -
Van Assche Evelien,
Moons Tim,
Cinar Ozan,
Viechtbauer Wolfgang,
Oldehinkel Albertine J.,
Van Leeuwen Karla,
Verschueren Karine,
Colpin Hilde,
Lambrechts Diether,
Van den Noortgate Wim,
Goossens Luc,
Claes Stephan,
Winkel Ruud
Publication year - 2017
Publication title -
journal of child psychology and psychiatry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.652
H-Index - 211
eISSN - 1469-7610
pISSN - 0021-9630
DOI - 10.1111/jcpp.12766
Subject(s) - psychology , gene , punishment (psychology) , linkage disequilibrium , snp , genetics , clinical psychology , behavioural genetics , developmental psychology , single nucleotide polymorphism , biology , genotype
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.