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- Bryois, J., et al.
(författare)
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Genetic identification of cell types underlying brain complex traits yields insights into the etiology of Parkinson’s disease
- 2020
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 52:5, s. 482-493
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies have discovered hundreds of loci associated with complex brain disorders, but it remains unclear in which cell types these loci are active. Here we integrate genome-wide association study results with single-cell transcriptomic data from the entire mouse nervous system to systematically identify cell types underlying brain complex traits. We show that psychiatric disorders are predominantly associated with projecting excitatory and inhibitory neurons. Neurological diseases were associated with different cell types, which is consistent with other lines of evidence. Notably, Parkinson’s disease was genetically associated not only with cholinergic and monoaminergic neurons (which include dopaminergic neurons) but also with enteric neurons and oligodendrocytes. Using post-mortem brain transcriptomic data, we confirmed alterations in these cells, even at the earliest stages of disease progression. Our study provides an important framework for understanding the cellular basis of complex brain maladies, and reveals an unexpected role of oligodendrocytes in Parkinson’s disease. © 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.
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| 5. |
- Xu, J., et al.
(författare)
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Exploring the clinical and genetic associations of adult weight trajectories using electronic health records in a racially diverse biobank: a phenome-wide and polygenic risk study
- 2022
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Ingår i: The Lancet Digital Health. - 2589-7500. ; 4:8, s. e604-e614
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Tidskriftsartikel (refereegranskat)abstract
- Background: Weight trajectories might reflect individual health status. In this study, we aimed to examine the clinical and genetic associations of adult weight trajectories using electronic health records (EHRs) in the BioMe Biobank. Methods: We constructed four weight trajectories based on a-priori definitions of weight changes (5% or 10%) using annual weight in EHRs (stable weight, weight gain, weight loss, and weight cycle); the final weight dataset included 21 487 participants with 162 783 annual weight measures. To confirm accurate assignment of weight trajectories, we manually reviewed weight trajectory plots for 100 random individuals. We then did a hypothesis-free phenome-wide association study (PheWAS) to identify diseases associated with each weight trajectory. Next, we estimated the single-nucleotide polymorphism-based heritability (hSNP2) of weight trajectories using GCTA-GREML, and we did a hypothesis-driven analysis of anorexia nervosa and depression polygenic risk scores (PRS) on these weight trajectories, given both diseases are associated with weight changes. We extended our analyses to the UK Biobank to replicate findings from a patient population to a generally healthy population. Findings: We found high concordance between manually assigned weight trajectories and those assigned by the algorithm (accuracy ≥98%). Stable weight was consistently associated with lower disease risks among those passing Bonferroni-corrected p value in our PheWAS (p≤4·4 × 10–5). Additionally, we identified an association between depression and weight cycle (odds ratio [OR] 1·42, 95% CI 1·31–1·55, p≤7·7 × 10–16). The adult weight trajectories were heritable (using 5% weight change as the cutoff: hSNP2 of 2·1%, 95% CI 0·9–3·3, for stable weight; 4·1%, 1·4–6·8, for weight gain; 5·5%, 2·8–8·2, for weight loss; and 4·7%, 2·3–7·1%, for weight cycle). Anorexia nervosa PRS was positively associated with weight loss trajectory among individuals without eating disorder diagnoses (OR1SD 1·16, 95% CI 1·07–1·26, per 1 SD higher PRS, p=0·011), and the association was not attenuated by obesity PRS. No association was found between depression PRS and weight trajectories after permutation tests. All main findings were replicated in the UK Biobank (p<0·05). Interpretation: Our findings suggest the importance of considering weight from a longitudinal aspect for its association with health and highlight a crucial role of weight management during disease development and progression. Funding: Klarman Family Foundation, US National Institute of Mental Health (NIMH). © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license
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| 6. |
- Birgegård, A, et al.
(författare)
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DSM-5: problems and suggestions
- 2013
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Ingår i: Journal of eating disorders. - : Springer Science and Business Media LLC. - 2050-2974. ; 1, s. 8-
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Tidskriftsartikel (refereegranskat)
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- Hansson, L M, et al.
(författare)
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How do eating disorder patients eat after treatment? Dietary habits and eating behaviour three years after entering treatment.
- 2011
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Ingår i: Eating and Weight Disorders. - 1124-4909 .- 1590-1262. ; 16:1, s. e1-8
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Improvements in psychological symptoms and weight have often been demonstrated following eating disorder (ED) treatment, but it is not clear to what extent eating behaviour itself is normalised. This cross-sectional study aimed to investigate dietary habits and eating behaviour in ED patients three years after entering treatment.METHOD: ED patients (N=70) were divided into those who had recovered (N=36), and those who still suffered from bulimic (N=18) or anorexic (N=16) psychopathology. Patients were compared to a female normal control group of similar age (N=61), and assessments were made on a dietary questionnaire, as well as the BDI, EDI-2, SASB and SCL-90.RESULTS: With some notable exceptions eating patterns in recovered patients resembled those of controls. Dieting was most evident in recovered and current bulimic patients, while restrictive eating and vegetarianism was found in recovered or current anorexic patients. A majority of the patients with ongoing EDs avoided fatty foods.DISCUSSION: Risk behaviours such as restrictive eating, dieting and food avoidance, may have an important impact on relapse rates, and it may therefore be imperative to continue to monitor eating behaviour in ED patients following treatment termination to ensure better long-term outcome.
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