| 1. |
- Wightman, D. P., et al.
(author)
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A genome-wide association study with 1,126,563 individuals identifies new risk loci for Alzheimer’s disease
- 2021
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In: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 53:9, s. 1276-1282
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Journal article (peer-reviewed)abstract
- Late-onset Alzheimer’s disease is a prevalent age-related polygenic disease that accounts for 50–70% of dementia cases. Currently, only a fraction of the genetic variants underlying Alzheimer’s disease have been identified. Here we show that increased sample sizes allowed identification of seven previously unidentified genetic loci contributing to Alzheimer’s disease. This study highlights microglia, immune cells and protein catabolism as relevant to late-onset Alzheimer’s disease, while identifying and prioritizing previously unidentified genes of potential interest. We anticipate that these results can be included in larger meta-analyses of Alzheimer’s disease to identify further genetic variants that contribute to Alzheimer’s pathology.
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| 2. |
- Jansen, I. E., et al.
(author)
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Genome-wide meta-analysis identifies new loci and functional pathways influencing Alzheimer’s disease risk
- 2019
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In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:3, s. 404-413
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Journal article (peer-reviewed)abstract
- Alzheimer’s disease (AD) is highly heritable and recent studies have identified over 20 disease-associated genomic loci. Yet these only explain a small proportion of the genetic variance, indicating that undiscovered loci remain. Here, we performed a large genome-wide association study of clinically diagnosed AD and AD-by-proxy (71,880 cases, 383,378 controls). AD-by-proxy, based on parental diagnoses, showed strong genetic correlation with AD (rg = 0.81). Meta-analysis identified 29 risk loci, implicating 215 potential causative genes. Associated genes are strongly expressed in immune-related tissues and cell types (spleen, liver, and microglia). Gene-set analyses indicate biological mechanisms involved in lipid-related processes and degradation of amyloid precursor proteins. We show strong genetic correlations with multiple health-related outcomes, and Mendelian randomization results suggest a protective effect of cognitive ability on AD risk. These results are a step forward in identifying the genetic factors that contribute to AD risk and add novel insights into the neurobiology of AD.
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| 3. |
- Kondo, M. C., et al.
(author)
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Momentary mood response to natural outdoor environments in four European cities
- 2020
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In: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 134
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Journal article (peer-reviewed)abstract
- Exposure to natural outdoor environments (NOE) has been shown in population-level studies to reduce anxiety and psychological distress. This study investigated how exposure to one's everyday natural outdoor environments over one week influenced mood among residents of four European cities including Barcelona (Spain), Stoke-on-Trent (United Kingdom), Doetinchem (The Netherlands) and Kaunas (Lithuania). Participants (n = 368) wore a smartphone equipped with software applications to track location and mood (using mobile ecological momentary assessment (EMA) software), for seven consecutive days. We estimated random-effects ordered logistic regression models to examine the association between mood (positive and negative affect), and exposure to green space, represented by two binary variables indicating exposure versus no exposure to NOE using GPS tracking and satellite and aerial imagery, 10 and 30 min prior to participants’ completing the EMA. Models were adjusted for home city, day of the week, hour of the day, EMA survey type, residential NOE exposure, and sex, age, education level, mental health status and neighbourhood socioeconomic status. In addition, we tested for heterogeneity of effect by city, sex, age, residential NOE exposure and mental health status. Within 10 min of NOE exposure, compared to non-exposure, we found that overall there was a positive relationship with positive affect (OR: 1.39, 95% CI: 1.06, 1.81) of EMA surveys, and non-significant negative association with negative affect (OR: 0.80, 95% CI: 0.58, 1.10). When stratifying, associations were consistently found for Stoke-on-Trent inhabitants and men, while findings by age group were inconsistent. Weaker and less consistent associations were found for exposure 30 min prior to EMA. Our findings support increasing evidence of psychological and mental health benefits of exposure to natural outdoor environments, especially among urban populations such as those included in our study.
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