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Genetic evidence for a large overlap and potential bidirectional causal effects between resilience and well-being.

ABSTRACT: Resilience and well-being are strongly related. People with higher levels of well-being are more resilient after stressful life events or trauma and vice versa. Less is known about the underlying sources of overlap and causality between the constructs. In a sample of 11.304 twins and 2.572 siblings from the Netherlands Twin Register, we investigated the overlap and possible direction of causation between resilience (i.e. the absence of psychiatric symptoms despite negative life events) and well-being (i.e. satisfaction with life) using polygenic score (PGS) prediction, twin-sibling modelling, and the Mendelian Randomization Direction of Causality (MR-DoC) model. Longitudinal twin-sibling models showed significant phenotypic correlations between resilience and well-being (.41/.51 at time 1 and 2). Well-being PGS were predictive for both well-being and resilience, indicating that genetic factors influencing well-being also predict resilience. Twin-sibling modeling confirmed this genetic correlation (0.71) and showed a strong environmental correlation (0.93). In line with causality, both genetic (51%) and environmental (49%) factors contributed significantly to the covariance between resilience and well-being. Furthermore, the results of within-subject and MZ twin differences analyses were in line with bidirectional causality. Additionally, we used the MR-DoC model combining both molecular and twin data to test causality, while correcting for pleiotropy. We confirmed the causal effect from well-being to resilience, with the direct effect of well-being explaining 11% (T1) and 20% (T2) of the variance in resilience. Data limitations prevented us to test the directional effect from resilience to well-being with the MR-DoC model. To conclude, we showed a strong relation between well-being and resilience. A first attempt to quantify the direction of this relationship points towards a bidirectional causal effect. If replicated, the potential mutual effects can have implications for interventions to lower psychopathology vulnerability, as resilience and well-being are both negatively related to psychopathology.

SUBMITTER: de Vries LP

PROVIDER: S-EPMC8010858 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionCigarette smokers are at increased risk of poor sleep behaviors. However, it is largely unknown whether these associations are due to shared (genetic) risk factors and/or causal effects (which may be bidirectional).MethodsWe obtained summary-level data of genome-wide association studies of smoking (smoking initiation [n = 74 035], cigarettes per day [n = 38 181], and smoking cessation [n = 41 278]) and sleep behaviors (sleep duration and chronotype, or "morningness" [n = 128 266] and insomnia [n = 113 006]). Using linkage disequilibrium (LD) score regression, we calculated genetic correlations between smoking and sleep behaviors. To investigate causal effects, we employed Mendelian randomization (MR), both with summary-level data and individual-level data (n = 333 581 UK Biobank participants). For MR with summary-level data, individual genetic variants were combined with inverse variance-weighted meta-analysis, weighted median regression, MR-Robust Adjusted Profile Score, and MR Egger methods.ResultsWe found negative genetic correlations between smoking initiation and sleep duration (rg = -.14, 95% CI = -0.26 to -0.01) and smoking cessation and chronotype (rg = -.18, 95% CI = -0.31 to -0.06), and positive genetic correlations between smoking initiation and insomnia (rg = .27, 95% CI = 0.06 to 0.49) and cigarettes per day and insomnia (rg = .15, 95% CI = 0.01 to 0.28). MR provided strong evidence that smoking more cigarettes causally decreases the odds of being a morning person, (RAPS) and weak evidence that insomnia causally increases smoking heaviness and decreases smoking cessation odds.ConclusionsSmoking and sleep behaviors show moderate genetic correlation. Heavier smoking seems to causally affect circadian rhythm and there is some indication that insomnia increases smoking heaviness and hampers cessation. Our findings point to sleep as a potentially interesting smoking treatment target.ImplicationsUsing LD score regression, we found evidence that smoking and different sleep behaviors (sleep duration, chronotype (morningness), and insomnia) are moderately genetically correlated-genetic variants associated with less or poorer sleep also increased the odds of smoking (more heavily). MR analyses suggested that heavier smoking causally affects circadian rhythm (decreasing the odds of being a morning person) and there was some indication that insomnia increases smoking heaviness and hampers smoking cessation. Our findings indicate a complex, bidirectional relationship between smoking and sleep behaviors and point to sleep as a potentially interesting smoking treatment target.

Project description:BackgroundSeveral observational studies and clinical trials have shown that the gut microbiota is associated with urological cancers. However, the causal relationship between gut microbiota and urological cancers remains to be elucidated due to many confounding factors.MethodsIn this study, we used two thresholds to identify gut microbiota GWAS from the MiBioGen consortium and obtained data for five urological cancers from the UK biobank and Finngen consortium, respectively. We then performed a two-sample Mendelian randomization (MR) analysis with Wald ratio or inverse variance weighted as the main method. We also performed comprehensive sensitivity analyses to verify the robustness of the results. In addition, we performed a reverse MR analysis to examine the direction of causality.ResultsOur study found that family Rikenellaceae, genus Allisonella, genus Lachnospiraceae UCG001, genus Oscillibacter, genus Eubacterium coprostanoligenes group, genus Eubacterium ruminantium group, genus Ruminococcaceae UCG013, and genus Senegalimassilia were related to bladder cancer; genus Ruminococcus torques group, genus Oscillibacter, genus Barnesiella, genus Butyricicoccus, and genus Ruminococcaceae UCG005 were related to prostate cancer; class Alphaproteobacteria, class Bacilli, family Family XI, genus Coprococcus2, genus Intestinimonas, genus Lachnoclostridium, genus Lactococcus, genus Ruminococcus torques group, and genus Eubacterium brachy group were related to renal cell cancer; family Clostridiaceae 1, family Christensenellaceae, genus Eubacterium coprostanoligenes group, genus Clostridium sensu stricto 1, and genus Eubacterium eligens group were related to renal pelvis cancer; family Peptostreptococcaceae, genus Romboutsia, and genus Subdoligranulum were related to testicular cancer. Comprehensive sensitivity analyses proved that our results were reliable.ConclusionsOur study confirms the role of specific gut microbial taxa on urological cancers, explores the mechanism of gut microbiota on urological cancers from a macroscopic level, provides potential targets for the screening and treatment of urological cancers, and is dedicated to providing new ideas for clinical research.

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Genetic evidence for a large overlap and potential bidirectional causal effects between resilience and well-being.

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