Dataset Information

Association Between Childhood Green Space, Genetic Liability, and the Incidence of Schizophrenia.

ABSTRACT: Childhood exposure to green space has previously been associated with lower risk of developing schizophrenia later in life. It is unclear whether this association is mediated by genetic liability or whether the 2 risk factors work additively. Here, we investigate possible gene-environment associations with the hazard ratio (HR) of schizophrenia by combining (1) an estimate of childhood exposure to residential-level green space based on the normalized difference vegetation index (NDVI) from Landsat satellite images, with (2) genetic liability estimates based on polygenic risk scores for 19 746 genotyped individuals from the Danish iPSYCH sample. We used information from the Danish registers of health, residential address, and socioeconomic status to adjust HR estimates for established confounders, ie, parents' socioeconomic status, and family history of mental illness. The adjusted HRs show that growing up surrounded by the highest compared to the lowest decile of NDVI was associated with a 0.52-fold (95% confidence interval [CI]: 0.40 to 0.66) lower schizophrenia risk, and children with the highest polygenic risk score had a 1.24-fold (95% CI: 1.18 to 1.30) higher schizophrenia risk. We found that NDVI explained 1.45% (95% CI: 1.07 to 1.90) of the variance on the liability scale, while polygenic risk score for schizophrenia explained 1.01% (95% CI: 0.77 to 1.46). Together they explained 2.40% (95% CI: 1.99 to 3.07) with no indication of a gene-environment interaction (P = .29). Our results suggest that risk of schizophrenia is associated additively with green space exposure and genetic liability, and provide no support for an environment-gene interaction between NDVI and schizophrenia.

SUBMITTER: Engemann K

PROVIDER: S-EPMC8496913 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Association Between Childhood Green Space, Genetic Liability, and the Incidence of Schizophrenia.

Engemann Kristine K Pedersen Carsten Bøcker CB Agerbo Esben E Arge Lars L Børglum Anders Dupont AD Erikstrup Christian C Hertel Ole O Hougaard David Michael DM McGrath John J JJ Mors Ole O Mortensen Preben Bo PB Nordentoft Merete M Sabel Clive Eric CE Sigsgaard Torben T Tsirogiannis Constantinos C Vilhjálmsson Bjarni Jóhann BJ Werge Thomas T Svenning Jens-Christian JC Horsdal Henriette Thisted HT

Schizophrenia bulletin 20201201 6

Childhood exposure to green space has previously been associated with lower risk of developing schizophrenia later in life. It is unclear whether this association is mediated by genetic liability or whether the 2 risk factors work additively. Here, we investigate possible gene-environment associations with the hazard ratio (HR) of schizophrenia by combining (1) an estimate of childhood exposure to residential-level green space based on the normalized difference vegetation index (NDVI) from Lands ...[more]

PMID: 32415773

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Project description:BackgroundIndividuals with schizophrenia are at higher risk of physical illnesses, which are a major contributor to their 20-year reduced life expectancy. It is currently unknown what causes the increased risk of physical illness in schizophrenia.AimsTo link genetic data from a clinically ascertained sample of individuals with schizophrenia to anonymised National Health Service (NHS) records. To assess (a) rates of physical illness in those with schizophrenia, and (b) whether physical illness in schizophrenia is associated with genetic liability.MethodWe linked genetic data from a clinically ascertained sample of individuals with schizophrenia (Cardiff Cognition in Schizophrenia participants, n = 896) to anonymised NHS records held in the Secure Anonymised Information Linkage (SAIL) databank. Physical illnesses were defined from the General Practice Database and Patient Episode Database for Wales. Genetic liability for schizophrenia was indexed by (a) rare copy number variants (CNVs), and (b) polygenic risk scores.ResultsIndividuals with schizophrenia in SAIL had increased rates of epilepsy (standardised rate ratio (SRR) = 5.34), intellectual disability (SRR = 3.11), type 2 diabetes (SRR = 2.45), congenital disorders (SRR = 1.77), ischaemic heart disease (SRR = 1.57) and smoking (SRR = 1.44) in comparison with the general SAIL population. In those with schizophrenia, carrier status for schizophrenia-associated CNVs and neurodevelopmental disorder-associated CNVs was associated with height (P = 0.015-0.017), with carriers being 7.5-7.7 cm shorter than non-carriers. We did not find evidence that the increased rates of poor physical health outcomes in schizophrenia were associated with genetic liability for the disorder.ConclusionsThis study demonstrates the value of and potential for linking genetic data from clinically ascertained research studies to anonymised health records. The increased risk for physical illness in schizophrenia is not caused by genetic liability for the disorder.

Project description:BackgroundAccess to green space has been hypothesized to have a beneficial impact on children's mental well-being and cognitive development. The underlying mechanisms of the mental health benefits of green space are not fully understood, but different pathways have been suggested, such as the psychologically restoring capacities of green space, the ability to facilitate physical activity and social cohesion, and the mitigation of exposure to air pollution.ObjectivesIn this nationwide cohort study, we investigated associations between residential green space in early childhood and a clinical diagnosis of attention deficit hyperactivity disorder (ADHD).MethodsThe cohort included individuals, who were born in Denmark between 1992 and 2007 (n=814,689) and followed for a diagnosis of ADHD from age 5, during the period 1997-2016. We used the normalized difference vegetation index (NDVI) as a measure of vegetation greenness surrounding each residential address in a quadratic area of 210m×210m in which the residence was located in the center of the quadrate. Individual exposure to green space was calculated as the average of NDVI surrounding each individual's residential address (or addresses if more than one) between birth and the fifth birthday. Multilevel modeling was used to estimate the incidence rate ratios (IRRs) with 95% confidence intervals (CI) for ADHD, according to exposure level and adjusted for calendar time, age, sex, parental socioeconomic status, neighborhood level socioeconomic status, and urbanicity.ResultsIndividuals living in areas defined by sparse green vegetation (lowest decile of NDVI) had an increased risk of developing ADHD, compared with individuals living in areas within the highest decile of NDVI (IRR=1.55; 95% CI: 1.46, 1.65). Adjusting for the known confounders attenuated the result, but the association remained (IRR=1.20; 95% CI: 1.13, 1.28).ConclusionOur findings suggest that lower levels of green space in residential surroundings, during early childhood, may be associated with a higher risk of developing ADHD. https://doi.org/10.1289/EHP6729.

Project description:ImportanceSchizophrenia is a clinically heterogeneous disorder. It is currently unclear how variability in symptom dimensions and cognitive ability is associated with genetic liability for schizophrenia.ObjectiveTo determine whether phenotypic dimensions within schizophrenia are associated with genetic liability to schizophrenia, other neuropsychiatric disorders, and intelligence.Design, setting, and participantsIn a genetic association study, 3 cross-sectional samples of 1220 individuals with a diagnosis of schizophrenia were recruited from community, inpatient, and voluntary sector mental health services across the UK. Confirmatory factor analysis was used to create phenotypic dimensions from lifetime ratings of the Scale for the Assessment of Positive Symptoms, Scale for the Assessment of Negative Symptoms, and the MATRICS Consensus Cognitive Battery. Analyses of polygenic risk scores (PRSs) were used to assess whether genetic liability to schizophrenia, other neuropsychiatric disorders, and intelligence were associated with these phenotypic dimensions. Data collection for the cross-sectional studies occurred between 1993 and 2016. Data analysis for this study occurred between January 2019 and March 2021.Main outcomes and measuresOutcome measures included phenotypic dimensions defined from confirmatory factor analysis relating to positive symptoms, negative symptoms of diminished expressivity, negative symptoms of motivation and pleasure, disorganized symptoms, and current cognitive ability. Exposure measures included PRSs for schizophrenia, bipolar disorder, major depression, attention-deficit/hyperactivity disorder, autism spectrum disorder, and intelligence.ResultsOf the 1220 study participants, 817 were men (67.0%). Participants' mean (SD) age at interview was 43.10 (12.74) years. Schizophrenia PRS was associated with increased disorganized symptom dimension scores in both a 5-factor model (β = 0.14; 95% CI, 0.07-0.22; P = 2.80 × 10-4) and a 3-factor model across all samples (β = 0.10; 95% CI, 0.05-0.15; P = 2.80 × 10-4). Current cognitive ability was associated with genetic liability to schizophrenia (β = -0.11; 95% CI, -0.19 to -0.04; P = 1.63 × 10-3) and intelligence (β = 0.23; 95% CI, 0.16-0.30; P = 1.52 × 10-10). After controlling for estimated premorbid IQ, current cognitive performance was associated with schizophrenia PRS (β = -0.08; 95% CI, -0.14 to -0.02; P = 8.50 × 10-3) but not intelligence PRS.Conclusions and relevanceThe findings of this study suggest that genetic liability for schizophrenia is associated with higher disorganized dimension scores but not other symptom dimensions. Cognitive performance in schizophrenia appears to reflect distinct contributions from genetic liabilities to both intelligence and schizophrenia.

Project description:Green space has a variety of health benefits. However, little is known about its impact on autism, the fastest-growing neurodevelopmental disorder in children. This study examined the relationship between green space and childhood autism prevalence. Autism count data in 2010 were obtained for 543 of ~560 public elementary school districts in California. Multiple types of green space were measured in each school district, including percentages of forest, grassland, and average tree canopy and near-road tree canopy. Their associations with autism prevalence were evaluated with negative binomial regression models and spatial regression models. We observed inverse associations between several green space metrics and autism prevalence in school districts with high road density, the highly urbanized areas, but not in others. According to negative binomial regression models, adjusted rate ratios (RR) for the relationships in these school districts between autism prevalence and green space metrics in 10% increments were as follows: for forest, RR=0.90 (95% confidence interval [CI]: 0.84-0.95); for grassland, RR=0.90 (95% CI: 0.83-0.97); for average tree canopy, RR=0.89 (95% CI: 0.83-0.95), and for near-road tree canopy, RR=0.81 (95% CI: 0.73-0.91). These results suggest that increases of 10% in forest, grassland, average tree canopy and near-road tree canopy are associated with a decrease in autism prevalence of 10%, 10% 11% and 19%, respectively. In contrast, urban land and road density were positively associated with autism prevalence. The results of spatial regression models were consistent with those obtained by negative binomial models, except for grassland. Our study suggests that green space, specifically tree cover in areas with high road density, may influence autism prevalence in elementary school children beneficially. Further studies are needed to investigate a potential causal relationship, and the major mechanisms that may underlie the beneficial associations with green space, such as buffering traffic-related air pollution and noise.

Dataset Information

Association Between Childhood Green Space, Genetic Liability, and the Incidence of Schizophrenia.

Publications

Association Between Childhood Green Space, Genetic Liability, and the Incidence of Schizophrenia.

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