scholarly journals Association of polygenic risk scores, traumatic life events and coping strategies with war-related PTSD diagnosis and symptom severity in the South Eastern Europe (SEE)-PTSD cohort

2021 ◽  
Author(s):  
Heike Weber ◽  
Adam X. Maihofer ◽  
Nenad Jaksic ◽  
Elma Feric Bojic ◽  
Sabina Kucukalic ◽  
...  
Keyword(s):  
Environmental Factors ◽  
Coping Strategies ◽  
Eastern Europe ◽  
Life Events ◽  
Symptom Severity ◽  
Risk Scores ◽  
Polygenic Risk ◽  
Ptsd Diagnosis ◽  
Traumatic Life Events ◽  
South Eastern Europe

Abstract Objectives Posttraumatic stress disorder (PTSD) is triggered by extremely stressful environmental events and characterized by high emotional distress, re-experiencing of trauma, avoidance and hypervigilance. The present study uses polygenic risk scores (PRS) derived from the UK Biobank (UKBB) mega-cohort analysis as part of the PGC PTSD GWAS effort to determine the heritable basis of PTSD in the South Eastern Europe (SEE)-PTSD cohort. We further analyzed the relation between PRS and additional disease-related variables, such as number and intensity of life events, coping, sex and age at war on PTSD and CAPS as outcome variables. Methods Association of PRS, number and intensity of life events, coping, sex and age on PTSD were calculated using logistic regression in a total of 321 subjects with current and remitted PTSD and 337 controls previously subjected to traumatic events but not having PTSD. In addition, PRS and other disease-related variables were tested for association with PTSD symptom severity, measured by the Clinician Administrated PTSD Scale (CAPS) by liner regression. To assess the relationship between the main outcomes PTSD diagnosis and symptom severity, each of the examined variables was adjusted for all other PTSD related variables. Results The categorical analysis showed significant polygenic risk in patients with remitted PTSD and the total sample, whereas no effects were found on symptom severity. Intensity of life events as well as the individual coping style were significantly associated with PTSD diagnosis in both current and remitted cases. The dimensional analyses showed as association of war-related frequency of trauma with symptom severity, whereas the intensity of trauma yielded significant results independently of trauma timing in current PTSD. Conclusions The present PRS application in the SEE-PTSD cohort confirms modest but significant polygenic risk for PTSD diagnosis. Environmental factors, mainly the intensity of traumatic life events and negative coping strategies, yielded associations with PTSD both categorically and dimensionally with more significant p-values. This suggests that, at least in the present cohort of war-related trauma, the association of environmental factors and current individual coping strategies with PTSD psychopathology was stronger than the polygenic risk.

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 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.

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 NEW APPROACH TO STUDYING COLLECTIVE EFFECTS OF GENETIC FACTORS ON ALZHEIMER’S DISEASE

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S96-S96
Author(s):  
Anatoliy Yashin ◽  
Deqing Wu ◽  
Konstantin Arbeev ◽  
Igor Akushevich ◽  
Arseniy Yashkin ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Environmental Factors ◽  
Specific Interaction ◽  
Risk Scores ◽  
Cardiovascular Health Study ◽  
Specific Gene ◽  
New Approach ◽  
Polygenic Risk ◽  
Genetic And Environmental Factors

Abstract Despite the wide recognition of the multifactorial nature of Alzheimer’s disease (AD), mechanisms of the collective influence of genetic and environmental factors on AD remain poorly understood. We used the Cardiovascular Health Study (CHS) and Framingham Heart Study (FHS) data to investigate the effects of genetic and gene-environment interactions on AD prevalence in the association analysis using logistic regression. Based on results of this analysis, we developed several new measures of integrated effects of SNPs, including for specific gene or group of genes, by constructing SNP-specific Interaction Polygenic Risk Scores (SIPRSs), Gene-specific Interaction Polygenic Risk Scores (GIPRS), and Trait-specific Interaction Polygenic Risk Scores (TIPRS), and tested them in the above data. We found strong interaction effects on AD among the SNPs in NRG3 gene and smoking, and among the SNPs in ATM and creatinine. In summary, we developed a new approach to measuring the collective impact of SNPs on complex traits, and discovered significant effects of the newly constructed SIPRS, GIPRS, and TIPRS on AD prevalence. The results of this study open a new opportunity of investigating the joint impacts of genetic and environmental factors on AD and other phenotypes of aging and health.

scholarly journals From climate zone to microhabitat—environmental factors affecting the coastal distribution of tiger beetles (Coleoptera: Cicindelidae) in the south-eastern European biodiversity hotspot

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e6676 ◽  
Author(s):  
Radomir Jaskuła ◽  
Mateusz Płóciennik ◽  
Axel Schwerk
Keyword(s):  
Environmental Factors ◽  
Eastern Europe ◽  
Environmental Changes ◽  
Soil Parameters ◽  
Factors Affecting ◽  
Tiger Beetle ◽  
Tiger Beetles ◽  
South Eastern ◽  
South Eastern Europe ◽  
Habitat Specialists

BackgroundTiger beetles (Coleoptera: Cicindelidae) are predatory insects usually occurring in various sandy habitats. In south-eastern Europe, especially in lowland areas located close to the sea coast, the diversity of Cicindelidae is one of the highest in the Palaearctic realm. Although previous studies conducted in different areas of the world show that many species are habitat specialists, unfortunately little is known about environmental factors affecting the diversity and distribution of tiger beetles in this region.Material and MethodsHabitat preferences for 12 tiger beetles taxa were analysed. Over 100 samples collected in eight countries located in coastal areas of the Black and Mediterranean Seas were studied, for which climate data, macrohabitat types, and soil parameters (soil humidity, salinity, pH, and structure) were investigated.ResultsMost studied Cicindelidae were characterised by narrow or very narrow habitat specialisation and did not co-occur with other ones, including 11 taxa found as habitat specialists occurring only in one or two types of macrohabitat. The most eurythopic species wasCalomera littoralis nemoraliswhich occupied four macrohabitat types. The climatic zone, altitude, and humidity were found as the most important factors in the distribution of the studied tiger beetle species. Salt marshes and sandy sea beaches were noted as the most diverse macrohabitat types.DiscussionTiger beetle fauna of south-eastern Europe consists mainly of habitat specialists sensitive to environmental changes, which makes these beetles perfect bioindicators. Moreover, as a great number of studied Cicindelidae taxa occur in habitats which are under a significant human impact, we suggest that in the studied area the group can be successfully used as a flagship taxon for insect and nature conservation.

scholarly journals Genetic and shared couple environmental contributions to smoking and alcohol use in the UK population

2019 ◽  
Author(s):  
Toni-Kim Clarke ◽  
Mark J. Adams ◽  
David M. Howard ◽  
Charley Xia ◽  
Gail Davies ◽  
...  
Keyword(s):  
Substance Use ◽  
Alcohol Use ◽  
Environmental Factors ◽  
Assortative Mating ◽  
Family Environment ◽  
Alcohol Intake ◽  
Risk Scores ◽  
Phenotypic Variance ◽  
Polygenic Risk ◽  
The Uk

AbstractAlcohol use and smoking are leading causes of death and disability worldwide. Both genetic and environmental factors have been shown to influence individual differences in the use of these substances. In the present study we tested whether genetic factors, modelled alongside common family environment, explained phenotypic variance in alcohol use and smoking behaviour in the Generation Scotland (GS) family sample of up to 19,377 individuals. SNP and pedigree-associated effects combined explained between 18 and 41% of the variance in substance use. Shared couple effects explained a significant amount of variance across all substance use traits, particularly alcohol intake, for which 38% of the phenotypic variance was explained. We tested whether the within-couple substance use associations were due to assortative mating by testing the association between partner polygenic risk scores in 34,987 couple pairs from the UK Biobank (UKB). No significant association between partner polygenic risk scores were observed. Associations between an individual's alcohol PRS (b = 0.05, S.E. = 0.006, p < 2 × 10−16) and smoking status PRS (b = 0.05, S.E. = 0.005, p < 2 × 10−16) were found with their partner’s phenotype. In support of this, G carriers of a functional ADH1B polymorphism (rs1229984), known to be associated with greater alcohol intake, were found to consume less alcohol if they had a partner who carried an A allele at this SNP. Together these results show that the shared couple environment contributes significantly to patterns of substance use. It is unclear whether this is due to shared environmental factors, assortative mating, or indirect genetic effects. Future studies would benefit from longitudinal data and larger sample sizes to assess this further.

Understanding Why Older People Develop a Wish to Die

Crisis ◽  
2011 ◽  
Vol 32 (4) ◽  
pp. 204-216 ◽  
Author(s):  
M. L. Rurup ◽  
H. R. W. Pasman ◽  
J. Goedhart ◽  
D. J. H. Deeg ◽  
A. J. F. M. Kerkhof ◽  
...  
Keyword(s):  
Older People ◽  
Cohort Studies ◽  
Conceptual Framework ◽  
Life Events ◽  
Traumatic Life Events ◽  
Quantitative Studies ◽  
Wish To Die ◽  
Open Coding ◽  
Death Wishes ◽  
Depth Interviews

Background: Quantitative studies in several European countries showed that 10–20% of older people have or have had a wish to die. Aims: To improve our understanding of why some older people develop a wish to die. Methods: In-depth interviews with people with a wish to die (n = 31) were carried out. Through open coding and inductive analysis, we developed a conceptual framework to describe the development of death wishes. Respondents were selected from two cohort studies. Results: The wish to die had either been triggered suddenly after traumatic life events or had developed gradually after a life full of adversity, as a consequence of aging or illness, or after recurring depression. The respondents were in a situation they considered unacceptable, yet they felt they had no control to change their situation and thus progressively “gave up” trying. Recurring themes included being widowed, feeling lonely, being a victim, being dependent, and wanting to be useful. Developing thoughts about death as a positive thing or a release from problems seemed to them like a way to reclaim control. Conclusions: People who wish to die originally develop thoughts about death as a positive solution to life events or to an adverse situation, and eventually reach a balance of the wish to live and to die.

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