Genetic overlap and causal associations between smoking behaviours and mental health.
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ABSTRACT:
SUBMITTER: Barkhuizen W
PROVIDER: S-EPMC8295327 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveCOVID-19 might cause neuroinflammation in the brain, which could decrease neurocognitive function. We aimed to evaluate the causal associations and genetic overlap between COVID-19 and intelligence.MethodsWe performed Mendelian randomization (MR) analyses to assess potential associations between three COVID-19 outcomes and intelligence (N = 269 867). The COVID phenotypes included severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (N = 2 501 486), hospitalized COVID-19 (N = 1 965 329) and critical COVID-19 (N = 743 167). Genome-wide risk genes were compared between the genome-wide association study (GWAS) datasets on hospitalized COVID-19 and intelligence. In addition, functional pathways were constructed to explore molecular connections between COVID-19 and intelligence.ResultsThe MR analyses indicated that genetic liabilities to SARS-CoV-2 infection (odds ratio [OR]: 0.965, 95% confidence interval [CI]: 0.939-0.993) and critical COVID-19 (OR: 0.989, 95% CI: 0.979-0.999) confer causal effects on intelligence. There was suggestive evidence supporting the causal effect of hospitalized COVID-19 on intelligence (OR: 0.988, 95% CI: 0.972-1.003). Hospitalized COVID-19 and intelligence share 10 risk genes within 2 genomic loci, including MAPT and WNT3. Enrichment analysis showed that these genes are functionally connected within distinct subnetworks of 30 phenotypes linked to cognitive decline. The functional pathway revealed that COVID-19-driven pathological changes within the brain and multiple peripheral systems may lead to cognitive impairment.ConclusionsOur study suggests that COVID-19 may exert a detrimental effect on intelligence. The tau protein and Wnt signaling may mediate the influence of COVID-19 on intelligence.
| S-EPMC10559337 | biostudies-literature
Project description:BackgroundMental health has worsened, and substance use has increased for some people during the coronavirus (COVID-19) pandemic. Some cross-sectional studies suggest that higher COVID-19 risk perceptions are related to poorer mental health and greater risk behaviours (e.g., substance use). However, longitudinal and genetic data are needed to help to reduce the likelihood of reverse causality.MethodsWe used cross-sectional, longitudinal, and polygenic risk score (PRS; for anxiety, depression, wellbeing) data from the Avon Longitudinal Study of Parents and Children (ALSPAC). We examined cross-sectional and prospective longitudinal associations between COVID-19 risk perceptions (i.e., cognitive, affective, self, other, and a combined 'holistic' measure) and mental health (i.e., anxiety, depression), wellbeing, and risk behaviours. Pandemic (April-July 2020) and pre-pandemic (2003-2017) data (ns = 233-5,115) were included.ResultsHigher COVID-19 risk perceptions (holistic) were associated with anxiety (OR 2.78, 95% confidence interval [CI] 2.20 to 3.52), depression (OR 1.65, 95% CI 1.24 to 2.18), low wellbeing (OR 1.76, 95% CI 1.45 to 2.13), and increased alcohol use (OR 1.46, 95% CI 1.24 to 1.72). Higher COVID-19 risk perceptions were also associated with self-isolating given a suspected COVID-19 infection (OR 1.74, 95% CI 1.13 to 2.68), and less face-to-face contact (OR 0.83, 95% CI 0.70 to 0.98) and physical contact (OR 0.83, 95% CI 0.68 to 1.00). Pre-pandemic anxiety (OR 1.64, 95% CI 1.29 to 2.09) and low wellbeing (OR 1.41, 95% CI 1.15 to 1.74) were associated with higher COVID-19 risk perceptions. The depression PRS (b 0.21, 95% CI 0.02 to 0.40) and wellbeing PRS (b -0.29, 95% CI -0.48 to -0.09) were associated with higher and lower COVID-19 risk perceptions, respectively.ConclusionsPoorer mental health and wellbeing are associated with higher COVID-19 risk perceptions, and longitudinal and genetic data suggest that they may play a causal role in COVID-19 risk perceptions.
| S-EPMC7615237 | biostudies-literature
Project description:ObjectiveLeveraging large-scale genetic data, we aimed to identify shared pathogenic mechanisms and causal relationships between impaired kidney function and cerebrovascular disease phenotypes.MethodsWe used summary statistics from genome-wide association studies (GWAS) of kidney function traits (chronic kidney disease diagnosis, estimated glomerular filtration rate [eGFR], and urinary albumin-to-creatinine ratio [UACR]) and cerebrovascular disease phenotypes (ischemic stroke and its subtypes, intracerebral hemorrhage [ICH], and white matter hyperintensities [WMH] on brain MRI). We (1) tested the genetic overlap between them with polygenic risk scores (PRS), (2) searched for common pleiotropic loci with pairwise GWAS analyses, and (3) explored causal associations by employing 2-sample Mendelian randomization.ResultsA PRS for lower eGFR was associated with higher large artery stroke (LAS) risk (p = 1 × 10-4). Multiple pleiotropic loci were identified between kidney function traits and cerebrovascular disease phenotypes, with 12q24 associated with eGFR and both LAS and small vessel stroke (SVS), and 2q33 associated with UACR and both SVS and WMH. Mendelian randomization revealed associations of both lower eGFR (odds ratio [OR] per 1-log decrement, 2.10; 95% confidence interval [CI], 1.38-3.21) and higher UACR (OR per 1-log increment, 2.35; 95% CI, 1.12-4.94) with a higher risk of LAS, as well as between higher UACR and higher risk of ICH.ConclusionsImpaired kidney function, as assessed by decreased eGFR and increased UACR, may be causally involved in the pathogenesis of LAS. Increased UACR, previously proposed as a marker of systemic small vessel disease, is involved in ICH risk and shares a genetic risk factor at 2q33 with manifestations of cerebral small vessel disease.
| S-EPMC7455337 | biostudies-literature
Project description:IntroductionWe sought to examine the genetic overlap between vascular pathologies and Alzheimer's disease (AD) dementia, and the potential mediating role of vascular pathologies between AD-related genetic variants and late-life cognition.MethodsFor 2907 stroke-free older individuals, we examined the association of polygenic risk scores for AD dementia (ADPRSs) with vascular pathologies and with cognition. Mediation analyses addressed whether association between ADPRSs and cognition was mediated by a vascular pathology.ResultsADPRSs were associated with lobar cerebral microbleeds, white matter lesion load, and coronary artery calcification, mostly explained by single nucleotide polymorphisms in the 19q13 region. The effect of ADPRSs on cognition was partially but significantly mediated by cerebral microbleeds, white matter lesions, and coronary artery calcification.DiscussionOur findings provide evidence for genetic overlap, mostly due to apolipoprotein E (APOE) gene, between vascular pathologies and AD dementia. The association between AD polygenic risk and late-life cognition is mediated in part via effects on vascular pathologies.
| S-EPMC6435328 | biostudies-literature
Project description:We applied a massively parallel reporter assay (MPRA) in lymphoblastoid cells to functionally evaluate 49,256 allelic pairs, representing 30,893 genetic variants in high, local linkage disequilibrium for 744 independent cis-expression quantitative trait loci (eQTLs) assessed for colocalization across 114 traits.
2021-05-24 | GSE174534 | GEO
Project description:Smoking is a major contributor to the disparity in life expectancy between those with and without a mental health condition. Previous work has found associations between individual conditions such as depression and current smoking, cigarette consumption and dependence, but did not compare a range of specific mental disorders. Using data from the nationally-representative Adult Psychiatric Morbidity Survey, we characterised trends in smoking prevalence in the general population in Great Britain and among those with and without mental health conditions for the period 1993-2014. We tested associations across different common mental health conditions (including depression, phobia, generalised anxiety and mixed anxiety and depression), in addition to personality conditions, and heaviness of smoking, desire to quit, perceived difficulty of remaining abstinent and successful cessation within the previous 12 months. Smoking prevalence among those without any mental health condition decreased from 29.3% in 1993 to 19.6% in 2014. Prevalence was higher among those with a condition but fell from 44.6% to 34.1%. Having a mental health condition was associated with current smoking, heavy smoking, difficulty remaining abstinent, desire to quit and perceived difficulty remaining abstinent. The same was found for all conditions individually but the strength and significance of the associations varied. Having any common mental health condition was associated with lower odds of smoking cessation-but not after adjustment for heavy smoking. We found no significant associations between individual conditions and cessation outcomes, however. In summary, smoking prevalence among people with common mental health conditions remained around 50% higher than among those without despite their higher desire to quit. Adequately addressing higher dependence could support cessation and contribute to narrowing health disparities.
| S-EPMC6334164 | biostudies-literature
Project description:Observationally, higher caffeine consumption is associated with poorer sleep and insomnia. We investigated whether these associations are a result of shared genetic risk factors and/or (possibly bidirectional) causal effects. Summary-level data were available from genome-wide association studies on caffeine intake (n = 91 462), plasma caffeine and caffeine metabolic rate (n = 9876), sleep duration and chronotype (being a "morning" versus an "evening" person) (n = 128 266), and insomnia complaints (n = 113 006). First, genetic correlations were calculated, reflecting the extent to which genetic variants influencing caffeine consumption and those influencing sleep overlap. Next, causal effects were estimated with bidirectional, two-sample Mendelian randomization. This approach utilizes the genetic variants most robustly associated with an exposure variable as an "instrument" to test causal effects. Estimates from individual variants were combined using inverse-variance weighted meta-analysis, weighted median regression and MR-Egger regression. We found no clear evidence for a genetic correlation between caffeine intake and sleep duration (rg = 0.000, p = .998), chronotype (rg = 0.086, p = .192) or insomnia complaints (rg = -0.034, p = .700). For plasma caffeine and caffeine metabolic rate, genetic correlations could not be calculated because of the small sample size. Mendelian randomization did not support causal effects of caffeine intake on sleep, or vice versa. There was weak evidence that higher plasma caffeine levels causally decrease the odds of being a morning person. Although caffeine may acutely affect sleep when taken shortly before bedtime, our findings suggest that a sustained pattern of high caffeine consumption is more likely to be associated with poorer sleep through shared environmental factors. Future research should identify such environments, which could aid the development of interventions to improve sleep.
| S-EPMC6175249 | biostudies-literature
Project description:Accumulating evidence from genome wide association studies (GWAS) suggests an abundance of shared genetic influences among complex human traits and disorders, such as mental disorders. Here we introduce a statistical tool, MiXeR, which quantifies polygenic overlap irrespective of genetic correlation, using GWAS summary statistics. MiXeR results are presented as a Venn diagram of unique and shared polygenic components across traits. At 90% of SNP-heritability explained for each phenotype, MiXeR estimates that 8.3 K variants causally influence schizophrenia and 6.4 K influence bipolar disorder. Among these variants, 6.2 K are shared between the disorders, which have a high genetic correlation. Further, MiXeR uncovers polygenic overlap between schizophrenia and educational attainment. Despite a genetic correlation close to zero, the phenotypes share 8.3 K causal variants, while 2.5 K additional variants influence only educational attainment. By considering the polygenicity, discoverability and heritability of complex phenotypes, MiXeR analysis may improve our understanding of cross-trait genetic architectures.
| S-EPMC6547727 | biostudies-literature
Project description:PurposeThe purpose of this study was to describe the genetic relationship between smoking and glaucoma.MethodsWe used summary-level genetic data for smoking initiation, smoking intensity (cigarettes per day [CPD]), intraocular pressure (IOP), vertical cup-disc ratio, and open-angle glaucoma (OAG) to estimate global genetic correlations (rg) and perform two-sample Mendelian randomization (MR) experiments that explored relations between traits. Finally, we examined associations between smoking genetic risk scores (GRS) and smoking traits with measured IOP and OAG in Rotterdam Study participants.ResultsWe identified weak inverse rg between smoking- and glaucoma-related traits that were insignificant after Bonferroni correction. However, MR analysis revealed that genetically predicted smoking initiation was associated with lower IOP (-0.18 mm Hg per SD, 95% confidence interval [CI] = -0.30 to -0.06, P = 0.003). Furthermore, genetically predicted smoking intensity was associated with decreased OAG risk (odds ratio [OR] = 0.74 per SD, 95% CI = 0.61 to 0.90, P = 0.002). In the Rotterdam Study, the smoking initiation GRS was associated with lower IOP (-0.09 mm Hg per SD, 95% CI = -0.17 to -0.01, P = 0.04) and lower odds of OAG (OR = 0.84 per SD, 95% CI = 0.73 to 0.98, P = 0.02) in multivariable-adjusted analyses. In contrast, neither smoking history nor CPD was associated with IOP (P ≥ 0.38) or OAG (P ≥ 0.54). Associations between the smoking intensity GRS and glaucoma traits were null (P ≥ 0.13).ConclusionsMR experiments and GRS generated from Rotterdam Study participants support an inverse relationship between smoking and glaucoma.Translational relevanceUnderstanding the genetic drivers of the inverse relationship between smoking and glaucoma could yield new insights into glaucoma pathophysiology.
| S-EPMC9932549 | biostudies-literature
Project description:ObjectiveSMI (severe mental illness) has been identified as a risk factor for sepsis in observational studies; however, the causal association between them has yet to be firmly established. We conducted MR (mendelian randomization) to unveil the causal relationship between SMI and sepsis as well as sepsis mortality.MethodsGWAS (Genome-wide association) data for major depression and schizophrenia were selected as exposure. GWAS data for sepsis and sepsis mortality were selected as outcome. Genetic variants significantly associated with the exposure (P value<1x10-6) were selected as instruments. We primarily employed the IVW (inverse-variance weighted) method for analysis. Furthermore, we employed Cochrane's Q test to assess heterogeneity and the MR-Egger intercept test to identify horizontal pleiotropy.ResultsWe selected 108 SNPs (single nucleotide polymorphism) used to predict major depression and 260 SNPs that predicted schizophrenia. Genetically predicted major depression was suggestively linked to a higher sepsis risk (OR=1.13, 95%CI 1.02-1.26, P=0.023). In contrast, MR analysis did not find an association between schizophrenia and sepsis risk (OR=1.00, 95%CI 0.97-1.04, P=0.811). Furthermore, no significant causal evidence was found for genetically predicted SMI in sepsis mortality. Moreover, no heterogeneity and horizontal pleiotropy were detected.ConclusionOur research revealed a suggestive association between genetically predicted major depression and an elevated risk of sepsis in individuals of European ancestry. This finding can serve as a reminder for clinicians to consider the possibility of subsequent infection and sepsis in depressive patients, which may help reduce the incidence of sepsis in individuals with depression.
| S-EPMC10964346 | biostudies-literature