Gene–Environment Interaction Effects of Peer Deviance, Parental Knowledge and Stressful Life Events on Adolescent Alcohol Use

The purpose of this study was to address two methodological issues that have called into question whether previously reported gene–environment interaction (GxE) effects for adolescent alcohol use are ‘real’. These issues are (1) the potential correlation between the environmental moderator and the outcome across twins and (2) non-linear transformations of the behavioral outcome. Three environments that have been previously studied (peer deviance, parental knowledge, and potentially stressful life events) were examined here. For each moderator (peer deviance, parental knowledge, and potentially stressful life events), a series of models was fit to both a raw and transformed measure of monthly adolescent alcohol use in a sample that included 825 dizygotic (DZ) and 803 monozygotic (MZ) twin pairs. The results showed that the moderating effect of peer deviance was robust to transformation, and that although the significance of moderating effects of parental knowledge and potentially stressful life events were dependent on the scale of the adolescent alcohol use outcome, the overall results were consistent across transformation. In addition, the findings did not vary across statistical models. The consistency of the peer deviance results and the shift of the parental knowledge and potentially stressful life events results between trending and significant, shed some light on why previous findings for certain moderators have been inconsistent and emphasize the importance of considering both methodological issues and previous findings when conducting and interpreting GxE analyses.

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Vulnerability to early stressful life events: The moderating role of HOMER1 gene in the gene × environment interaction

European Journal of Developmental Psychology ◽

10.1080/17405629.2021.2011717 ◽

2022 ◽

pp. 1-23

Author(s):

Yidi Chen ◽

Lizhong Wang ◽

Dongdong Jiang ◽

Shanshan Zhu ◽

WeGene Research Team ◽

...

Keyword(s):

Life Events ◽

Stressful Life Events ◽

Stressful Life ◽

Environment Interaction ◽

Gene Environment Interaction ◽

Gene Environment ◽

Moderating Role

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Do polygenic risk and stressful life events predict pharmacological treatment response in obsessive compulsive disorder? A gene–environment interaction approach

Translational Psychiatry ◽

10.1038/s41398-019-0410-0 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 7

Author(s):

María Alemany-Navarro ◽

Javier Costas ◽

Eva Real ◽

Cinto Segalàs ◽

Sara Bertolín ◽

...

Keyword(s):

Life Events ◽

Pharmacological Treatment ◽

Stressful Life Events ◽

Environment Interaction ◽

Obsessive Compulsive ◽

Polygenic Risk ◽

Compulsive Disorder ◽

Gene Environment Interaction ◽

Gene Environment ◽

Interaction Approach

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Gene–environment interactions between HPA-axis genes and stressful life events in depression: a systematic review

Acta Neuropsychiatrica ◽

10.1017/neu.2019.16 ◽

2019 ◽

Vol 31 (04) ◽

pp. 186-192 ◽

Cited By ~ 6

Author(s):

Caroline Normann ◽

Henriette N. Buttenschøn

Keyword(s):

Systematic Review ◽

Life Events ◽

Nuclear Receptor ◽

Hpa Axis ◽

Hormone Receptor ◽

Stressful Life Events ◽

Stressful Life ◽

Releasing Hormone ◽

Gene Environment ◽

Nuclear Receptor Subfamily

AbstractObjective:Depression is a disorder caused by genetics and environmental factors. The aim of this study was to perform a review investigating the interaction between genetic variations located in genes involved in hypothalamus–pituitary–adrenal axis (HPA-axis) and stressful life events (SLEs) in depression.Methods:In this systematic review, we selected articles investigating the interaction between genes involved in the HPA-axis, such as Arginine Vasopressin (AVP), Angiotensin Converting Enzyme (ACE), Corticotrophin Releasing Hormone (CRH), Corticotrophin Releasing Hormone Receptor 1 (CRHR1), Corticotrophin Releasing Hormone Receptor 2 (CRHR2), FK506 binding protein (FKBP5), Nuclear Receptor subfamily 3 group C member 1 (NR3C1), Nuclear Receptor subfamily 3 group C member 2 (NR3C2), and SLE. The literature search was conducted using the Pubmed, Embase, and PsychINFO databases in adherence with the PRISMA guidelines.Results:The search yielded 48 potentially relevant studies, of which 40 were excluded following screening. Eight studies were included in the final review. A total of 97 single nucleotide polymorphisms (SNPs) were examined in the eight included studies. The most prevalent gene was FKBP5, and the best studied polymorphism was FKBP5:rs1360780. Two of the five studies reported significant gene–environment (G × E) interactions between rs1360780 and SLE. Overall, four studies reported significant G × E interactions between FKBP5, CRH, or CRHR1 and SLE, respectively. No significant G × E interactions were found for the remaining genes.Conclusions:Our results suggest that genetic variation in three genes in the HPA-axis possibly moderate the effects of SLEs in depression.

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Stressful life events in early life and suicidal behaviour

European Psychiatry ◽

10.1016/s0924-9338(11)73865-2 ◽

2011 ◽

Vol 26 (S2) ◽

pp. 2162-2162

Author(s):

P.A. Saiz

Keyword(s):

Life Events ◽

Suicidal Behaviour ◽

Life Stress ◽

Stressful Life Events ◽

Negative Emotion ◽

Association Studies ◽

Stressful Life ◽

Environment Interaction ◽

Biological Stress ◽

S Allele

There is robust evidence that stressful life events (SLE) are associated with an increase in risk of developing depression. However, humans display wide variation in response to adversity. Caspi et al (2003) reported that a functional length polymorphism (5-HTTLPR) in the promoter of the serotonin transporter gene moderated the influence of SLE on depressive symptoms, major depression, and suicidality, suggesting evidences of a gene-by-environment interaction.Neuroimage data from healthy, non-depressed, s allele carriers of the 5-HTTLPR show an exaggerated amygdale response to threatening visual stimuli as well as reduced gray matter volume in limbic regions critical for processing of negative emotion compared with individuals with the LL genotype. These data suggest a potent modulatory effect of the 5-HTTLPR on amygdala reactivity to environmental threat.In recent years, a growing number of molecular genetic studies have focused on the serotonin system, suggesting that this system may be involved in the pathogenesis of suicidal behaviour. Meta-analytic evidences support a link between the s allele of the 5-HTTLPR and the risk of suicidal behaviour. However, several case-control association studies show an association between the short allele and the violence, the number, and the medical lethality of the attempts.On the other hand, recent data suggest that biological stress reactivity, mediated by the hypothalamic-pituitary-adrenocortical axis, might be a plausible mechanism underlying the association between the 5-HTTLPR genotype and exposure to life stress in predicting psychopathology.In this presentation we discuss data regarding the complex relationship between the above mentioned systems, stress, and suicidal behaviour.

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Genome-wide by environment interaction study of stressful life events and hospital-treated depression in the iPSYCH2012 sample

Biological Psychiatry Global Open Science ◽

10.1016/j.bpsgos.2021.11.003 ◽

2021 ◽

Author(s):

Nis P. Suppli ◽

Klaus K. Andersen ◽

Esben Agerbo ◽

Veera M. Rajagopal ◽

Vivek Appadurai ◽

...

Keyword(s):

Life Events ◽

Stressful Life Events ◽

Stressful Life ◽

Environment Interaction ◽

Interaction Study ◽

Genome Wide

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Adolescent Alcohol Use: The Effects of Parental Knowledge, Peer Substance Use, and Peer Tolerance of Use

Journal of the Society for Social Work and Research ◽

10.1086/695809 ◽

2018 ◽

Vol 9 (1) ◽

pp. 69-87 ◽

Cited By ~ 4

Author(s):

Christina M. Sellers ◽

Kimberly H. McManama O’Brien ◽

Lynn Hernandez ◽

Anthony Spirito

Keyword(s):

Substance Use ◽

Alcohol Use ◽

Parental Knowledge ◽

Adolescent Alcohol Use ◽

Adolescent Alcohol ◽

Peer Substance Use

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Pathogenesis

10.1093/med/9780199692736.003.0003 ◽

2012 ◽

Author(s):

Raymond W. Lam

Keyword(s):

Life Events ◽

Social Factors ◽

Stressful Life Events ◽

Stress Reactivity ◽

Stressful Life ◽

Neural Systems ◽

Biological Processes ◽

Novel Treatments ◽

Gene Environment ◽

Multiple Processes

• There are likely multiple processes to explain the etiology and pathophysiology of depression, with involvement of biological, psychological and social factors.• Circadian rhythmicity, stressful life events and stress reactivity can modify genetic and biological processes (gene-environment interactions) to contribute to depression.• Endophenotypes, or genetic expressions of neural systems involved in depression, will be important in the study of the pathogenesis of depression and the development of novel treatments....

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