| 1. |
- Bruder, Carl E G, et al.
(författare)
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Phenotypically concordant and discordant monozygotic twins display different DNA copy-number-variation profiles
- 2008
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 82:3, s. 763-71
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Tidskriftsartikel (refereegranskat)abstract
- The exploration of copy-number variation (CNV), notably of somatic cells, is an understudied aspect of genome biology. Any differences in the genetic makeup between twins derived from the same zygote represent an irrefutable example of somatic mosaicism. We studied 19 pairs of monozygotic twins with either concordant or discordant phenotype by using two platforms for genome-wide CNV analyses and showed that CNVs exist within pairs in both groups. These findings have an impact on our views of genotypic and phenotypic diversity in monozygotic twins and suggest that CNV analysis in phenotypically discordant monozygotic twins may provide a powerful tool for identifying disease-predisposition loci. Our results also imply that caution should be exercised when interpreting disease causality of de novo CNVs found in patients based on analysis of a single tissue in routine disease-related DNA diagnostics.
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| 2. |
- Evangelou, Evangelos, et al.
(författare)
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Non-replication of association for six polymorphisms from meta-analysis of genome-wide association studies of Parkinson's disease : large-scale collaborative study
- 2010
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Ingår i: American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics. - : Wiley. - 1552-4841 .- 1552-485X. ; 153B:1, s. 8-220
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Tidskriftsartikel (refereegranskat)abstract
- Early genome-wide association (GWA) studies on Parkinson's disease (PD) have not been able to yield conclusive, replicable signals of association, perhaps due to limited sample size. We aimed to investigate whether association signals derived from the meta-analysis of the first two GWA investigations might be replicable in different populations. We examined six single-nucleotide polymorphisms (SNPs) (rs1000291, rs1865997, rs2241743, rs2282048, rs2313982, and rs3018626) that had reached nominal significance with at least two of three different strategies proposed in a previous analysis of the original GWA studies. Investigators from the "Genetic Epidemiology of Parkinson's Disease" (GEOPD) consortium were invited to join in this study. Ten teams contributed replication data from 3,458 PD cases and 3,719 controls. The data from the two previously published GWAs (599 PD cases, 592 controls and 443 sibling pairs) were considered as well. All data were synthesized using both fixed and random effects models. The summary allelic odds ratios were ranging from 0.97 to 1.09 by random effects, when all data were included. The summary estimates of the replication data sets (excluding the original GWA data) were very close to 1.00 (range 0.98-1.09) and none of the effects were nominally statistically significant. The replication data sets had significantly different results than the GWA data. Our data do not support evidence that any of these six SNPs reflect susceptibility markers for PD. Much stronger signals of statistical significance in GWA platforms are needed to have substantial chances of replication. Specifically in PD genetics, this would require much larger GWA studies and perhaps novel analytical techniques.
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| 3. |
- Feldman, Adina L., et al.
(författare)
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Accuracy and Sensitivity of Parkinsonian Disorder Diagnoses in Two Swedish National Health Registers
- 2012
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Ingår i: Neuroepidemiology. - : S. Karger AG. - 1423-0208 .- 0251-5350. ; 38:3, s. 186-193
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Tidskriftsartikel (refereegranskat)abstract
- Background: Swedish population-based national health registers are widely used data sources in epidemiological research. Register-based diagnoses of Parkinson's disease have not been validated against clinical information. Methods: Parkinson's disease (PD) and other parkinsonian disorder diagnoses were ascertained in two registers, i.e. the National Patient Register (NPR) and the Cause of Death Register (CDR). Diagnoses were validated in terms of accuracy (positive predictive value) and sensitivity against data from a population-based study of PD in 1998-2004 that screened more than 35,000 persons and identified 194 cases of parkinsonian disorders including 132 PD cases (the gold standard for the purposes of this study). Results: Accuracy for any parkinsonian disorder diagnoses was 88.0% in the NPR and 94.4% in the CDR. Accuracy of PD diagnoses was 70.8% in the NPR and 66.7% in the CDR. Misclassification between differential parkinsonian diagnoses was common. The accuracy of PD diagnoses in the NPR improved to 83.0% by restricting the definition to primary diagnoses only. The sensitivity of PD diagnoses in the NPR and CDR combined was 83.1%, with a mean time to detection of 6.9 years. Conclusions: Population-based national health registers are valid data sources in epidemiological studies of PD or parkinsonian disorder etiology but are less suitable in studies of incidence or prevalence. Copyright (C) 2012 S. Karger AG, Basel
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| 4. |
- Kang, Xiaoying, et al.
(författare)
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Association between Microscopic Colitis and Parkinson's Disease in a Swedish Population
- 2021
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Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 96:15
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Tidskriftsartikel (refereegranskat)abstract
- Background: Gastrointestinal inflammation has been linked with Parkinson's disease (PD). Microscopic colitis (MC) is an intestinal inflammatory disease with unknown relationship with PD.Objective: This study aimed to examine the association of MC with PD risk.Methods: In this nationwide matched cohort study in Sweden, PD incidence was compared between 12,609 patients with histologically confirmed MC and a matched population cohort of 58,879 MC-free individuals and a sibling cohort comprising all unaffected siblings of the MC patients (N-MC/N-Sibling = 6281/12,351). Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression models.Results: During a mean follow-up of similar to 7 years, we identified 449 incident PD diagnoses among the MC patients and the population cohort. Overall, MC was associated with an adjusted HR of 1.76 for PD, but the association attenuated substantially during follow-up. In the time-varying effects model, PD hazard was 3.45-fold (95% CI: 2.42, 4.93) higher during the first 2 years after biopsy and 1.80-fold (95% CI: 1.23, 2.64) higher during the following 3 years among MC versus MC-free individuals but was not different beyond 5 years after biopsy (HR: 1.03; 95% CI: 0.68, 1.54). This temporal pattern of MC-PD associations persisted when comparing MC patients to their siblings. In a post hoc case-control analysis, we also detected a strong association between MC and preexisting PD (odds ratio: 3.46; 95% CI: 2.91, 4.12).Conclusions: Our findings suggest that MC may not be a risk factor for PD; instead, it may co-occur with PD as a comorbidity or develop after a diagnosis of PD.
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| 5. |
- Kang, Xiaoying, et al.
(författare)
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Clostridium difficile infection and risk of Parkinson's disease : A Swedish population-based cohort study
- 2020
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Ingår i: European Journal of Neurology. - : Blackwell Publishing. - 1351-5101 .- 1468-1331. ; 27:11, s. 2134-2141
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Gastrointestinal inflammation has been implicated in Parkinson's disease (PD). This study examined whether individuals with a history of Clostridium difficile infection (CDI) are at elevated risk of PD.METHODS: We performed a population-based cohort study using Swedish national register data. Adults aged ≥ 35 years were identified from the Swedish Population and Housing Census 1990 and followed during 1997-2013. Diagnoses of CDI and PD were extracted from the National Patient Register. Associations of CDI history with PD risk were estimated using Cox proportional hazards regression. We also explored whether the association differed by the source of CDI diagnosis (inpatient vs outpatient), presence of recurrent infections, and pre-infection use of antibiotics.RESULTS: Amongst the study population (N = 4,670,423), 34,868 (0.75%) had a history of CDI. A total of 165 and 47,035 incident PD cases were identified from individuals with and without CDI history, respectively. Across the entire follow-up, a 16% elevation of PD risk was observed among CDI group (hazard ratio: 1.16, 95% confidence interval: 1.00-1.36), which was mainly driven by increased PD risk within the first 2 years since CDI diagnosis (hazard ratio: 1.38, 95% confidence interval: 1.12-1.69). In longer follow-up, CDI was not associated with subsequent PD occurrence. This temporal pattern of CDI-PD associations was generally observed across all CDI subgroups.CONCLUSIONS: CDI may be associated with an increased short-term PD risk, but this might be explained by reverse causation and/or surveillance bias. Our results do not imply that CDI history affects long-term PD risk.
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| 6. |
- Liu, Bojing, et al.
(författare)
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Irritable bowel syndrome and Parkinson's disease risk : register-based studies
- 2021
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Ingår i: NPJ Parkinson's Disease. - : Nature Publishing Group. - 2373-8057. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- To examine whether irritable bowel syndrome (IBS) was related to the future risk of Parkinson's disease (PD), we conducted a nested case-control study in the Swedish total population including 56,564 PD cases identified from the Swedish Patient Register and 30 controls per case individually matched by sex and year of birth. Odds ratios (ORs) with 95% confidence intervals (CIs) for having a prior diagnosis of IBS were estimated using conditional logistic regression. We furthermore conducted a cohort study using the Swedish Twin Registry following 3046 IBS patients identified by self-reported abdominal symptoms and 41,179 non-IBS individuals. Through Cox proportional hazard models, we estimated hazard ratios (HRs) and 95% CIs for PD risk. In the nested case-control study, 253 (0.4%) PD cases and 5204 (0.3%) controls had a previous IBS diagnosis. IBS diagnosis was associated with a 44% higher risk of PD (OR = 1.44, 95% CI 1.27-1.63). Temporal relationship analyses showed 53% and 38% increased risk of PD more than 5 and 10 years after IBS diagnosis, respectively. In the cohort analysis based on the Swedish Twin Registry, there was no statistically significantly increased risk of PD related to IBS (HR = 1.25, 95% CI = 0.87-1.81). Our results suggest a higher risk of PD diagnosis after IBS. These results provide additional evidence supporting the importance of the gut-brain axis in PD.
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| 7. |
- Liu, Bojing, et al.
(författare)
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Vagotomy and Parkinson disease : A Swedish register-based matched-cohort study
- 2017
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Ingår i: Neurology. - : Lippincott Williams & Wilkins. - 0028-3878 .- 1526-632X. ; 88:21, s. 1996-2002
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To examine whether vagotomy decreases the risk of Parkinson disease (PD).Methods: Using data from nationwide Swedish registers, we conducted a matched-cohort study of 9,430 vagotomized patients (3,445 truncal and 5,978 selective) identified between 1970 and 2010 and 377,200 reference individuals from the general population individually matched to vagotomized patients by sex and year of birth with a 40: 1 ratio. Participants were followed up from the date of vagotomy until PD diagnosis, death, emigration out of Sweden, or December 31, 2010, whichever occurred first. Vagotomy and PD were identified from the Swedish Patient Register. We estimated hazard ratios (HRs) with 95% confidence intervals (CIs) using Cox models stratified by matching variables, adjusting for country of birth, chronic obstructive pulmonary disease, diabetes mellitus, vascular diseases, rheumatologic disease, osteoarthritis, and comorbidity index.Results: A total of 4,930 cases of incident PD were identified during 7.3 million person-years of follow-up. PD incidence (per 100,000 person-years) was 61.8 among vagotomized patients (80.4 for truncal and 55.1 for selective) and 67.5 among reference individuals. Overall, vagotomy was not associated with PD risk (HR 0.96, 95% CI 0.78-1.17). However, there was a suggestion of lower risk among patients with truncal vagotomy (HR 0.78, 95% CI 0.55-1.09), which may be driven by truncal vagotomy at least 5 years before PD diagnosis (HR 0.59, 95% CI 0.37-0.93). Selective vagotomy was not related to PD risk in any analyses.Conclusions: Although overall vagotomy was not associated the risk of PD, we found suggestive evidence for a potential protective effect of truncal, but not selective, vagotomy against PD development.
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| 8. |
- Liu, Bojing, et al.
(författare)
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β2-adrenoreceptor agonists, montelukast, and Parkinson's disease risk
- 2023
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Ingår i: Annals of Neurology. - : John Wiley & Sons. - 0364-5134 .- 1531-8249. ; 93:5, s. 1023-1028
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Tidskriftsartikel (refereegranskat)abstract
- Objective: This study was undertaken to examine the association between montelukast use, beta 2-adrenoreceptor (beta 2AR) agonist use, and later Parkinson disease (PD).Methods: We ascertained use of beta 2AR agonists (430,885 individuals) and montelukast (23,315 individuals) from July 1, 2005 to June 30, 2007, and followed 5,186,886 PD-free individuals from July 1, 2007 to December 31, 2013 for incident PD diagnosis. We estimated hazard ratios and 95% confidence intervals using Cox regressions.Results: We observed 16,383 PD cases during on average 6.1 years of follow-up. Overall, use of beta 2AR agonists and montelukast were not related to PD incidence. A 38% lower PD incidence was noted among high-dose montelukast users when restricted to PD registered as the primary diagnosis.Interpretation: Overall, our data do not support inverse associations between beta 2AR agonists, montelukast, and PD. The prospect of lower PD incidence with high-dose montelukast exposure warrants further investigation, especially with adjustment for high-quality data on smoking. ANN NEUROL 2023
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| 9. |
- Sieurin, Johanna, et al.
(författare)
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Occupational stress and risk for Parkinson's disease : A nationwide cohort study.
- 2018
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Ingår i: Movement Disorders. - : John Wiley & Sons Ltd. - 0885-3185 .- 1531-8257. ; 33:9, s. 1456-1464
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Stress has been suggested as a contributing factor in the etiology of Parkinson's Disease (PD), but epidemiological evidence is sparse.OBJECTIVE: The objective of this study was to explore the association between occupational stress according to the job demands-control model and the risk for PD.METHODS: We conducted a population-based cohort study with 2,544,748 Swedes born 1920 to 1950 who had an occupation reported in the population and housing censuses in 1980 or, if missing, in 1970. Job demands and control were measured using a job-exposure matrix. Incident PD cases were identified using Swedish national health registers from 1987 to 2010. Data were analyzed with Cox regression with age as the underlying time scale, adjusting for sex, education, and chronic obstructive pulmonary disease as a proxy for smoking.RESULTS: During a mean follow-up time of 21.3 years, 21,544 incident PD cases were identified. High demands were associated with increased PD risk among men, most evident in men with high education. High control was associated with increased PD risk among the low educated. This association was more pronounced in women. High-strain jobs (high demands and low control) was only associated with increased PDrisk among men with high education, whereas active jobs (high demands and high control) were associated with increased PD risk among men with low education.INTERPRETATION: High job demands appear to increase PD risk in men, especially in men with high education, whereas high job control increases PD risk among low educated, more strongly in women. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
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| 10. |
- Song, Huan, et al.
(författare)
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Association of Stress-Related Disorders With Subsequent Neurodegenerative Diseases
- 2020
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Ingår i: JAMA Neurology. - : American Medical Association. - 2168-6149 .- 2168-6157. ; 77:6, s. 700-709
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Posttraumatic stress disorder (PTSD) has been associated with increased risk for dementia. Less is known, however, about other stress-related disorders and their associations with neurodegenerative diseases.Objective: To examine the association between stress-related disorders and risk for neurodegenerative diseases.Design, Setting, and Participants: This population-matched and sibling cohort study was conducted in Sweden using data from nationwide health registers, including the Swedish National Patient Register. Individuals who received their first diagnosis of stress-related disorders between January 1, 1987, and December 31, 2008, were identified. Individuals who had a history of neurodegenerative diseases, had conflicting or missing information, had no data on family links, or were aged 40 years or younger at the end of the study were excluded. Individuals with stress-related disorders were compared with the general population in a matched cohort design; they were also compared with their siblings in a sibling cohort. Follow-up commenced from the age of 40 years or 5 years after the diagnosis of stress-related disorders, whichever came later, until the first diagnosis of a neurodegenerative disease, death, emigration, or the end of follow-up (December 31, 2013), whichever occurred first. Data analyses were performed from November 2018 to April 2019.Exposures: Diagnosis of stress-related disorders (PTSD, acute stress reaction, adjustment disorder, and other stress reactions).Main Outcomes and Measurements: Neurodegenerative diseases were identified through the National Patient Register and classified as primary or vascular. Alzheimer disease, Parkinson disease, and amyotrophic lateral sclerosis were evaluated separately. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) with 95% CIs after controlling for multiple confounders.Results: The population-matched cohort included 61 748 exposed individuals and 595 335 matched unexposed individuals. A total of 44 839 exposed individuals and their 78 482 unaffected full siblings were included in the sibling cohort analysis. The median (interquartile range) age at the start of follow-up was 47 (41-56) years, and 24 323 (39.4%) of the exposed individuals were male. The median (interquartile range) follow-up was 4.7 (2.1-9.8) years. Compared with unexposed individuals, individuals with a stress-related disorder were at an increased risk of neurodegenerative diseases (HR, 1.57; 95% CI, 1.43-1.73). The risk increase was greater for vascular neurodegenerative diseases (HR, 1.80; 95% CI, 1.40-2.31) than for primary neurodegenerative diseases (HR, 1.31; 95% CI, 1.15-1.48). A statistically significant association was found for Alzheimer disease (HR, 1.36; 95% CI, 1.12-1.67) but not Parkinson disease (HR, 1.20; 95% CI, 0.98-1.47) or amyotrophic lateral sclerosis (HR, 1.20; 95% CI, 0.74-1.96). Results from the sibling cohort corroborated results from the population-matched cohort.Conclusions and Relevance: This study showed an association between stress-related disorders and an increased risk of neurodegenerative diseases. The relative strength of this association for vascular neurodegenerative diseases suggests a potential cerebrovascular pathway.
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