Evelien Van Assche

Epigenome-Wide Analysis Of Methylation And Perceived Parenting In Adolescents And Its Correlation With Depressive Symptoms Over Time

Background Adolescents are continuously exposed to their parents. Previous research has shown that parenting can affect adolescents’ wellbeing. Prior research has also argued that adolescents’ impaired wellbeing can influence their performance over time. We present a study with an Illumina 450k array comparing methylation in adolescents reporting either perceived supportive-guiding or punishing-neglecting parenting at T0 and how these methylation differences are correlated with depressive symptoms over time. Methods Following a cluster analysis with a 6 cluster solution, 45 Belgian adolescents (Mage (SD) = 13.88 (0.90) at T0; 48% boys) from the STRATEGIES dataset (n= 1116) were randomly selected from the two most extreme clusters: perceived supportive-guiding parenting qnd punishing-neglecting. Perceived parenting was measured with the Leuven Adolescent Perceived Parenting Schale (LAPPS) and the Parental Behavior Scale (PBS). Methylation was measured with an Illumina Infinium HumanMethylation450 BeadChip. 1 individual was excluded after quality control (RnBeads, R), resulting in 44 adolescents for analysis. DMRs were identified using DMRcate (R) and comb-p (Python). We corrected for gender, batch, cell types (Horvath), and hidden stratification. The accuracy of the 450k-array was verified with Sequenom Epityper (min. r=.46, max. r= .97; p Results Only DMRs overlapping between the top 20 of DMRcate, ranked by “minpval” and comb-p at the e-2 (14 DMRs) and e-3 level (28 DMRs), were taken into account. Despite the major statistical differences in the two approaches, 13 DMRs overlapped between DMRcate and comb-p at the e-3 level. 4 additional DMRs overlapped when adding the e-2 level. Regions are annotated to the genes PEX10, ASCL2, KCNQ1, GPR19, DLL3, HDAC4, RFPL2, PPT2, ACAT2, KIF25, HOXA11, PTPRN2, and SCRIB. For the most significant CpG per region, only three CpGs were correlated with depressive symptoms at T2: cg13306335 in PEX10 (r= .47, p = .0014), cg05171197 in HDAC4 (r= .33, p = .021) and cg13417420 in GPR19 (r= .33, p= .030), with PEX10 surviving Bonferroni correction for 17 tests (p Discussion Despite our limited sample size, we show that two statistically different methods overlap highly in the regions they identify to be significantly different based on perceived parenting in this adolescent sample. Furthermore, we show that for PEX10 the methylation at the most significant CpG is more strongly correlated with depressive symptoms two years later (T2) than the cluster at T0 and depressive symptoms at T2. This raises the question if parenting in adolescents can affect methylation at T0, which may secondarily predispose some adolescents to depressive symptoms over time. More research in a larger and independent sample is needed to validate this preliminary hypothesis.

The role of parenting dimensions in depressive symptoms in adolescents and possible interactions with 5 well known VNTR's involved in neurotransmission

Background: Parenting dimensions are associatedwith depressive symptoms in adolescents. We investigated gene-environment interactions between perceived parenting dimensions and 5 well knownVariableNumber TandemRepeats (VNTR) in 4 genes associated with monoamine neurotransmission: 5-HTTLPR, STin2 in the serotonin transporter gene and theDAT1, DRD4 andMAOA repeats. Methods: A population sample of 1103 Belgian adolescents and their parents (mean age: 13.79 years, SD=0.94) were asked to fill out questionnaires. From each of them 5 VNTR’s were analyzed using DNA from saliva samples. Perceived parenting dimensions were explored using the LAPPS and VSOG self-report scale. After factor analysis, 5 factors were defined: support, proactive control, psychological control, punishmentandharshpunishment. Thephenotype “depressive symptoms” was investigated using the CES-D self-report scale. Statistical analyses were performed in R using linear regression techniques. Results: Perceived parenting dimensions,more specifically perceived support and psychological control, seem strongly associated with depressive symptoms as reported in CES-D (p<0.001). The only interaction effect that withstood multiple testing (p<0.0014) was seen for 5-HTTLPR and the difference in proactive control as perceived by the adolescents in comparison to the parental perception. Conclusions: Our results suggest that perceived parenting dimensions are strongly associated with depressive symptoms, as reported by the CES-D scale. We only found evidence for 5-HTTLPR to interact with the difference in perceived proactive control in the causation of depressive symptoms in adolescents.