scholarly journals Genetic and environmental determinants of stressful life events and their overlap with depression and neuroticism

2019 ◽  
Vol 3 ◽  
pp. 11 ◽  
Author(s):  
Toni-Kim Clarke ◽  
Yanni Zeng ◽  
Lauren Navrady ◽  
Charley Xia ◽  
Chris Haley ◽  
...  
Keyword(s):  
Risk Factors ◽  
Life Events ◽  
Stressful Life Events ◽  
Family Health ◽  
Stressful Life ◽  
Risk Scores ◽  
Health Study ◽  
Phenotypic Variance ◽  
Polygenic Risk ◽  
Genetic Overlap

Background: Stressful life events (SLEs) and neuroticism are risk factors for major depressive disorder (MDD). However, SLEs and neuroticism are heritable and genetic risk for SLEs is associated with risk for MDD. We sought to investigate the genetic and environmental contributions to SLEs in a family-based sample, and quantify genetic overlap with MDD and neuroticism. Methods: A subset of Generation Scotland: the Scottish Family Health Study (GS), consisting of 9618 individuals with information on MDD, past 6 month SLEs, neuroticism and genome-wide genotype data was used in the present study. We estimated the heritability of SLEs using GCTA software. The environmental contribution to SLEs was assessed by modelling familial, couple and sibling components. Using polygenic risk scores (PRS) and LD score regression (LDSC) we analysed the genetic overlap between MDD, neuroticism and SLEs. Results: Past 6-month life events were positively associated with lifetime MDD status (β=0.21, r2=1.1%, p=2.5 x 10-25) and neuroticism (β =0.13, r2=1.9%, p=1.04 x 10-37) at the phenotypic level.  Common SNPs explained 8% of the phenotypic variance in personal life events (those directly affecting the individual) (S.E.=0.03, p= 9 x 10-4). A significant effect of couple environment was detected accounting for 13% (S.E.=0.03, p=0.016) of the phenotypic variation in SLEs. PRS analyses found that reporting more SLEs was associated with a higher polygenic risk for MDD (β =0.05, r2=0.3%, p=3 x 10-5), but not a higher polygenic risk for neuroticism. LDSC showed a significant genetic correlation between SLEs and both MDD (rG=0.33, S.E.=0.08 ) and neuroticism (rG=0.15, S.E.=0.07). Conclusions: These findings suggest that SLEs should not be regarded solely as environmental risk factors for MDD as they are partially heritable and this heritability is shared with risk for MDD and neuroticism. Further work is needed to determine the causal direction and source of these associations.

scholarly journals Genetic and environmental determinants of stressful life events and their overlap with depression and neuroticism

2018 ◽  
Vol 3 ◽  
pp. 11 ◽  
Author(s):  
Toni-Kim Clarke ◽  
Yanni Zeng ◽  
Lauren Navrady ◽  
Charley Xia ◽  
Chris Haley ◽  
...  
Keyword(s):  
Risk Factors ◽  
Life Events ◽  
Stressful Life Events ◽  
Family Health ◽  
Stressful Life ◽  
Risk Scores ◽  
Health Study ◽  
Phenotypic Variance ◽  
Polygenic Risk ◽  
Genetic Overlap

Background: Stressful life events (SLEs) and neuroticism are risk factors for major depressive disorder (MDD). However, SLEs and neuroticism are heritable and genetic risk for SLEs is correlated with risk for MDD. We sought to investigate the genetic and environmental contributions to SLEs in a family-based sample, and quantify genetic overlap with MDD and neuroticism. Methods: A subset of Generation Scotland: the Scottish Family Health Study (GS), consisting of 9618 individuals with information on MDD, past 6 month SLEs, neuroticism and genome-wide genotype data was used in the present study. We estimated the heritability of SLEs using GCTA software. The environmental contribution to SLEs was assessed by modelling familial, couple and sibling components. Using polygenic risk scores (PRS) and LD score regression (LDSC) we analysed the genetic overlap between MDD, neuroticism and SLEs. Results: Past 6-month life events were positively correlated with lifetime MDD status (β=0.21, r2=1.1%, p=2.5 x 10-25) and neuroticism (β =0.13, r2=1.9%, p=1.04 x 10-37) at the phenotypic level.  Common SNPs explained 8% of the phenotypic variance in personal life events (those directly affecting the individual) (S.E.=0.03, p= 9 x 10-4). A significant effect of couple environment was detected accounting for 13% (S.E.=0.03, p=0.016) of the phenotypic variation in SLEs. PRS analyses found that reporting more SLEs was associated with a higher polygenic risk for MDD (β =0.05, r2=0.3%, p=3 x 10-5), but not a higher polygenic risk for neuroticism. LDSC showed a significant genetic correlation between SLEs and both MDD (rG=0.33, S.E.=0.08 ) and neuroticism (rG=0.15, S.E.=0.07). Conclusions: These findings suggest that SLEs should not be regarded solely as environmental risk factors for MDD as they are partially heritable and this heritability is shared with risk for MDD and neuroticism. Further work is needed to determine the causal direction and source of these associations.

scholarly journals Genetic and environmental determinants of stressful life events and their overlap with depression and neuroticism

2017 ◽  
Author(s):  
Toni-Kim Clarke ◽  
Yanni Zeng ◽  
Lauren Navrady ◽  
Charley Xia ◽  
Chris Haley ◽  
...  
Keyword(s):  
Life Events ◽  
Stressful Life Events ◽  
Molecular Genetic ◽  
Genetic Correlations ◽  
Family Health ◽  
Large Family ◽  
Stressful Life ◽  
Risk Scores ◽  
Health Study ◽  
Genetic Overlap

AbstractBackgroundStressful life events (SLEs) and neuroticism are risk factors for major depressive disorder (MDD). However, SLEs and neuroticism are heritable traits that are correlated with genetic risk for MDD. In the current study, we sought to investigate the genetic and environmental contributions to SLEs in a large family-based sample, and quantify any genetic overlap with MDD and neuroticism.MethodsA subset of Generation Scotland: the Scottish Family Health Study, consisting of 9618 individuals comprise the present study. We estimated the heritability of SLEs using pedigree-based and molecular genetic data. The environment was assessed by modelling familial, couple and sibling components. Using polygenic risk scores (PRS) and LD score regression we analysed the genetic overlap between MDD, neuroticism and SLEs.ResultsPast 6-month life events were positively correlated with lifetime MDD status (β=0.21, r2=1.1%, p=2.5 × 10−25) and neuroticism (β =0.13, r2=1.9%, p=1.04 × 10−37). Common SNPs explained 8% of the variance in personal life events (those directly affecting the individual) (S.E.=0.03, p=9 × 10−4). A significant effect of couple environment accounted for 13% (S.E.=0.03, p=0.016) of variation in SLEs. PRS analyses found that individuals with higher PRS for MDD reported more SLEs (β =0.05, r2=0.3%, p=3 × 10−5). LD score regression demonstrated genetic correlations between MDD and both SLEs (rG=0.33, S.E.=0.08) and neuroticism (rG=0.15, S.E.=0.07).ConclusionsThese findings suggest that SLEs are partially heritable and this heritability is shared with risk for MDD and neuroticism. Further work should determine the causal direction and source of these associations.

scholarly journals Nick Martin’s Contribution to GxE Research

2020 ◽  
Vol 23 (2) ◽  
pp. 131-134
Author(s):  
Lucía Colodro-Conde ◽  
Baptiste Couvy-Duchesne
Keyword(s):  
Life Events ◽  
Human Behavior ◽  
Stressful Life Events ◽  
Human Genetics ◽  
Empirical Support ◽  
Stressful Life ◽  
Risk Scores ◽  
Stress Model ◽  
Polygenic Risk ◽  
Diathesis Stress Model

AbstractThe study and identification of genotype–environment interactions (GxE) has been a hot topic in the field of human genetics for several decades. Yet the extent to which GxE contributes to human behavior variability, and its mechanisms, remains largely unknown. Nick Martin has contributed important advances to the field of GxE for human behavior, which include methodological developments, novel analyses and reviews. Here, we will first review Nick’s contributions to the GxE research, which started during his PhD and consistently appears in many of his over 1000 publications. Then, we recount a project that led to an article testing the diathesis-stress model for the origins of depression. In this publication, we observed the presence of an interaction between polygenic risk scores for depression (the risk in our ‘genotype’) and stressful life events (the experiences from our ‘environment’), which provided the first empirical support of this model.

Life events and psychosocial factors in elderly suicides – a case–control study

2001 ◽  
Vol 31 (7) ◽  
pp. 1193-1202 ◽  
Author(s):  
E. RUBENOWITZ ◽  
M. WAERN ◽  
K. WILHELMSON ◽  
P. ALLEBECK
Keyword(s):  
Risk Factors ◽  
Mental Disorder ◽  
Life Events ◽  
Stressful Life Events ◽  
Significant Risk ◽  
Stressful Life ◽  
Elderly Persons ◽  
Somatic Illness ◽  
Family Discord ◽  
Population Controls

Background. Stressful life events, such as family conflicts, separation, bereavement, somatic illness and financial problems are common antecedents of suicide. Studies on suicide among younger persons dominate the literature, despite the fact that a large proportion of suicides occur among elderly persons.Methods. The occurrence of stressful life events was investigated among elderly suicide cases and population controls. The study was conducted in the southwestern part of Sweden and included 85 persons (46 males and 39 females) 65 years and above who had committed suicide from January 1994 to May 1996. Population controls (84 males and 69 females) were randomly selected. Interviews were carried out with the controls and with informants for the suicide cases. Questions on sociodemographic background, mental and somatic health status, and life events (0–6, 7–12 and 13–24 months preceding suicide/interview) were included in the interviews.Results. Somatic illness, family discord and financial trouble were significant risk factors during all three time periods. Other risk factors were mental disorder, lower education, feelings of loneliness and previous suicide in the family. Factors associated with a decreased risk included active participation in organizations and having a hobby. Variables that remained in the multivariate logistic regression model were mental disorder (men, odds ratio (OR) = 62·4, 95% CI 17·9–217·5; women, OR = 55·9, 95% CI 14·1–222·3) and family discord (men, OR = 10·0, 95% CI 1·7–59·8; women, OR = 9·2, 95% CI 1·9–44·8).Conclusions. Mental disorder and family discord were the two major risk factors for suicide among elderly men and women.

A functional neuregulin-1 gene variant and stressful life events: Effect on drug use in a longitudinal population-representative cohort study

2016 ◽  
Vol 31 (1) ◽  
pp. 54-61 ◽  
Author(s):  
Mariliis Vaht ◽  
Kariina Laas ◽  
Evelyn Kiive ◽  
Jüri Parik ◽  
Toomas Veidebaum ◽  
...  
Keyword(s):  
Substance Use ◽  
Drug Use ◽  
Life Events ◽  
Illicit Drugs ◽  
Substance Dependence ◽  
Stressful Life Events ◽  
Susceptibility Gene ◽  
Stressful Life ◽  
Health Study ◽  
Neuregulin 1

Background: The neuregulin 1 gene is a susceptibility gene for substance dependence. A functional polymorphism (SNP8NRG243177/rs6994992; C/T) in the promoter region of the brain-specific type IV neuregulin-1 gene ( NRG1) has been associated with psychiatric disorders (e.g. schizophrenia and bipolar disorder) that often present higher odds of smoking, alcohol and illicit drug use. This study assessed the association of the NRG1 genotype with drug use and possible interaction with stressful life events (SLEs). Methods: The database of the Estonian Children Personality Behaviour and Health Study (beginning in 1998) was used. Cohorts of children initially 9 years old ( n=583; followed up at 15 and 18 years) and 15 years old ( n=593; followed up at 18 and 25 years) provided self-reports on alcohol, tobacco and illicit substance use and SLEs. Psychiatric assessment based on DSM-IV was carried out on the older birth cohort at age 25 to assess the lifetime presence of substance use disorders. NRG1 rs6994992 was genotyped in all participants by TaqMan® Pre-Designed SNP Genotyping Assay on the Applied Biosystems ViiA™ 7 Real-Time PCR System. The minor (T) allele frequency was 0.37. Results: NRG1 rs6994992 C/C homozygotes, especially those who had experienced more SLEs, were more likely to develop alcohol use disorders by young adulthood, were generally more active consumers of tobacco products, and had more likely used illicit drugs. In T allele carriers, SLEs had a negligible effect on substance use. Conclusions: In humans, NRG1 genotype is associated with substance use, and this relationship is moderated by adverse life events, with a gain-of-function allele being protective.

scholarly journals Depression is more than the sum score of its parts: individual DSM symptoms have different risk factors

2013 ◽  
Vol 44 (10) ◽  
pp. 2067-2076 ◽  
Author(s):  
E. I. Fried ◽  
R. M. Nesse ◽  
K. Zivin ◽  
C. Guille ◽  
S. Sen
Keyword(s):  
Risk Factors ◽  
Life Events ◽  
Stressful Life Events ◽  
Disease Model ◽  
Work Hours ◽  
Stressful Life ◽  
Childhood Stress ◽  
Dsm 5 ◽  
Patient Health ◽  
Sum Scores

BackgroundFor diagnostic purposes, the nine symptoms that compose the DSM-5 criteria for major depressive disorder (MDD) are assumed to be interchangeable indicators of one underlying disorder, implying that they should all have similar risk factors. The present study investigates this hypothesis, using a population cohort that shifts from low to elevated depression levels.MethodWe assessed the nine DSM-5 MDD criterion symptoms (using the Patient Health Questionnaire; PHQ-9) and seven depression risk factors (personal and family MDD history, sex, childhood stress, neuroticism, work hours, and stressful life events) in a longitudinal study of medical interns prior to and throughout internship (n = 1289). We tested whether risk factors varied across symptoms, and whether a latent disease model could account for heterogeneity between symptoms.ResultsAll MDD symptoms increased significantly during residency training. Four risk factors predicted increases in unique subsets of PHQ-9 symptoms over time (depression history, childhood stress, sex, and stressful life events), whereas neuroticism and work hours predicted increases in all symptoms, albeit to varying magnitudes. MDD family history did not predict increases in any symptom. The strong heterogeneity of associations persisted after controlling for a latent depression factor.ConclusionsThe influence of risk factors varies substantially across DSM depression criterion symptoms. As symptoms are etiologically heterogeneous, considering individual symptoms in addition to depression diagnosis might offer important insights obfuscated by symptom sum scores.

scholarly journals Polygenic risk, stressful life events and depressive symptoms in older adults: a polygenic score analysis

2014 ◽  
Vol 45 (8) ◽  
pp. 1709-1720 ◽  
Author(s):  
K. L. Musliner ◽  
F. Seifuddin ◽  
J. A. Judy ◽  
M. Pirooznia ◽  
F. S. Goes ◽  
...  
Keyword(s):  
Older Adults ◽  
Depressive Symptoms ◽  
Life Events ◽  
Stressful Life Events ◽  
Negative Binomial ◽  
Depression Scale ◽  
Stressful Life ◽  
Stressful Event ◽  
Polygenic Risk ◽  
Polygenic Scores

Background.Previous studies suggest that the relationship between genetic risk and depression may be moderated by stressful life events (SLEs). The goal of this study was to assess whether SLEs moderate the association between polygenic risk of major depressive disorder (MDD) and depressive symptoms in older adults.Method.We used logistic and negative binomial regressions to assess the associations between polygenic risk, SLEs and depressive symptoms in a sample of 8761 participants from the Health and Retirement Study. Polygenic scores were derived from the Psychiatric Genomics Consortium genome-wide association study of MDD. SLEs were operationalized as a dichotomous variable indicating whether participants had experienced at least one stressful event during the previous 2 years. Depressive symptoms were measured using an eight-item Center for Epidemiologic Studies Depression Scale subscale and operationalized as both a dichotomous and a count variable.Results.The odds of reporting four or more depressive symptoms were over twice as high among individuals who experienced at least one SLE (odds ratio 2.19, 95% confidence interval 1.86–2.58). Polygenic scores were significantly associated with depressive symptoms (β= 0.21,p⩽ 0.0001), although the variance explained was modest (pseudor2= 0.0095). None of the interaction terms for polygenic scores and SLEs was statistically significant.Conclusions.Polygenic risk and SLEs are robust, independent predictors of depressive symptoms in older adults. Consistent with an additive model, we found no evidence that SLEs moderated the association between common variant polygenic risk and depressive symptoms.

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