| 1. |
- Cruz, Raquel, et al.
(författare)
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Novel genes and sex differences in COVID-19 severity
- 2022
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Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 31:22, s. 3789-3806
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Tidskriftsartikel (refereegranskat)abstract
- Here, we describe the results of a genome-wide study conducted in 11 939 coronavirus disease 2019 (COVID-19) positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (P < 5 × 10−8) was crossed for variants in 3p21.31 and 21q22.11 loci only among males (P = 1.3 × 10−22 and P = 8.1 × 10−12, respectively), and for variants in 9q21.32 near TLE1 only among females (P = 4.4 × 10−8). In a second phase, results were combined with an independent Spanish cohort (1598 COVID-19 cases and 1068 population controls), revealing in the overall analysis two novel risk loci in 9p13.3 and 19q13.12, with fine-mapping prioritized variants functionally associated with AQP3 (P = 2.7 × 10−8) and ARHGAP33 (P = 1.3 × 10−8), respectively. The meta-analysis of both phases with four European studies stratified by sex from the Host Genetics Initiative (HGI) confirmed the association of the 3p21.31 and 21q22.11 loci predominantly in males and replicated a recently reported variant in 11p13 (ELF5, P = 4.1 × 10−8). Six of the COVID-19 HGI discovered loci were replicated and an HGI-based genetic risk score predicted the severity strata in SCOURGE. We also found more SNP-heritability and larger heritability differences by age (<60 or ≥60 years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided.
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| 2. |
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| 3. |
- Le Guen, Yann, et al.
(författare)
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Multiancestry analysis of the HLA locus in Alzheimer's and Parkinson's diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes.
- 2023
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 1091-6490 .- 0027-8424. ; 120:36
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Tidskriftsartikel (refereegranskat)abstract
- Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson's disease (PD) and Alzheimer's disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues.
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| 4. |
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| 5. |
- Axelsson Fisk, Sten, et al.
(författare)
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Chronic Obstructive Pulmonary Disease in Sweden: an intersectional multilevel analysis of individual heterogeneity and discriminatory accuracy
- 2018
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Ingår i: SSM - Population Health. - : Elsevier BV. - 2352-8273. ; 4, s. 334-346
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Tidskriftsartikel (refereegranskat)abstract
- Socioeconomic, ethnic and gender disparities in Chronic Obstructive Pulmonary Disease (COPD) risk are well established but no studies have applied multilevel analysis of individual heterogeneity and discriminatory accuracy (MAIHDA) within an intersectional framework to study this outcome. We study individuals at the first level of analysis and combinations of multiple social and demographic categorizations (i.e., intersectional strata) at the second level of analysis. Here we used MAIHDA to assess to what extent individual differences in the propensity of developing COPD are at the intersectional strata level. We also used MAIHDA to determine the degree of similarity in COPD incidence of individuals in the same intersectional stratum. This leads to an improved understanding of risk heterogeneity and of the social dynamics driving socioeconomic and demographic disparities in COPD incidence. Using data from 2,445,501 residents in Sweden aged 45–65, we constructed 96 intersectional strata combining categories of age, gender, income, education, civil- and migration status. The incidences of COPD ranged from 0.02% for young, native males with high income and high education who cohabited to 0.98% for older native females with low income and low education who lived alone. We calculated the intra-class correlation coefficient (ICC) that informs on the discriminatory accuracy of the categorizations. In a model that conflated additive and interaction effects, the ICC was good (20.0%). In contrast, in a model that measured only interaction effects, the ICC was poor (1.1%) suggesting that most of the observed differences in COPD incidence across strata are due to the main effects of the categories used to construct the intersectional matrix while only a minor share of the differences are attributable to intersectional interactions. We found conclusive interaction effects. The intersectional MAIHDA approach offers improved information to guide public health policies in COPD prevention, and such policies should adopt an intersectional perspective.
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| 6. |
- Axelsson Fisk, Sten, et al.
(författare)
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Understanding the complexity of socioeconomic disparities in smoking prevalence in sweden : A cross-sectional study applying intersectionality theory
- 2021
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Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 11:2
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Socioeconomic disparities in smoking prevalence remain a challenge to public health. The objective of this study was to present a simple methodology that displays intersectional patterns of smoking and quantify heterogeneities within groups to avoid inappropriate and potentially stigmatising conclusions exclusively based on group averages. Setting This is a cross-sectional observational study based on data from the National Health Surveys for Sweden (2004-2016 and 2018) including 136 301 individuals. We excluded people under 30 years of age, or missing information on education, household composition or smoking habits. The final sample consisted on 110 044 individuals or 80.7% of the original sample. Outcome Applying intersectional analysis of individual heterogeneity and discriminatory accuracy (AIHDA), we investigated the risk of self-reported smoking across 72 intersectional strata defined by age, gender, educational achievement, migration status and household composition. Results The distribution of smoking habit risk in the population was very heterogeneous. For instance, immigrant men aged 30-44 with low educational achievement that lived alone had a prevalence of smoking of 54% (95% CI 44% to 64%), around nine times higher than native women aged 65-84 with high educational achievement and living with other(s) that had a prevalence of 6% (95% CI 5% to 7%). The discriminatory accuracy of the information was moderate. Conclusion A more detailed, intersectional mapping of the socioeconomic and demographic disparities of smoking can assist in public health management aiming to eliminate this unhealthy habit from the community. Intersectionality theory together with AIHDA provides information that can guide resource allocation according to the concept proportionate universalism.
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| 7. |
- Bjerkeli, Pernilla J., et al.
(författare)
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Overuse of methylphenidate : an analysis of Swedish pharmacy dispensing data
- 2018
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Ingår i: Clinical Epidemiology. - : Dove Press. - 1179-1349. ; 10, s. 1657-1665
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To identify overuse of methylphenidate and to investigate patterns of overuse in relation to sociodemographic and clinical characteristics. Patients and methods: Swedish national, pharmacy dispensing data were analyzed for all 56,922 individuals aged 6-79 years, who filled a methylphenidate prescription between 2010 and 2011. Overuse was defined as having above 150% days covered by the dispensed amount during 365 days from the first prescription fill, assuming use at the maximum recommended daily dose. Results: In total, 4,304 individuals (7.6% of the methylphenidate users) were categorized as overusers. The risk of overuse increased with age (OR for 46-65 years vs 6-12 years 17.5, 95% CI 14.3-21.3), and was higher in men (OR 1.4, 95% CI 1.3-1.5) and individuals with low income (OR 1.1, 95% CI 1.0-1.2), as well as in individuals with an attention deficit hyperactivity disorder (ADHD) diagnosis (OR 1.4, 95% CI 1.3-1.6), health care visits (OR 1.3, 95% CI 1.2-1.4), previous ADHD medication use (OR 2.6, 95% CI 2.4-2.8), and previous diagnosis of mental and behavioral disorders due to psychoactive substance use (OR 2.1 95% CI 2.0-2.3). Conclusion: Among individuals using methylphenidate in Sweden, 7.6% receive amounts that are larger than what they should have a medical need for, assuming that they were using the maximum recommended daily dose 365 days per year. Notably, the prevalence of overuse was associated with previous diagnosis of alcohol and drug misuse. The prevalence was also positively associated with higher age and previous use of ADHD medication. These findings may point toward a link between exposure time and overuse. However, future studies with long-term data are needed to investigate this.
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| 8. |
- Cantarero Arevalo, Lourdes, et al.
(författare)
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Ethnic differences in asthma treatment among Swedish adolescents: A multilevel analysis of individual heterogeneity.
- 2016
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Ingår i: Scandinavian Journal of Public Health. - : SAGE Publications. - 1651-1905 .- 1403-4948. ; 44:2, s. 94-184
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Tidskriftsartikel (refereegranskat)abstract
- Adolescents with immigrant or ethnic minority background suffering from asthma receive on average less appropriate anti-asthmatic medication (AAM) than the majority population. However, those findings are based on analyses of differences between group averages which prevents our understanding of individual heterogeneity around the averages. Taking into account individual socioeconomic factors and medical needs, we performed multilevel analysis in order to evaluate if maternal country of birth (MCOB) accurately identifies adolescents with inappropriate AAM use.
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| 9. |
- Hornborg, Christoffer, 1982, et al.
(författare)
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Socioeconomic disparities in attention deficit hyperactivity disorder (ADHD) in Sweden: An intersectional ecological niches analysis of individual heterogeneity and discriminatory accuracy (IEN-AIHDA).
- 2023
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Ingår i: PloS one. - 1932-6203. ; 18:11
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Tidskriftsartikel (refereegranskat)abstract
- We aimed (i) to gain a better understanding of the demographic and socioeconomical distribution of ADHD risk in Sweden; and (ii) to contribute to the critical discussion on medicalization, i.e., the tendency to define and treat behavioural and social problems as medical entities. For this purpose, we analysed the risk of suffering from ADHD in the whole Swedish population aged between 5 and 60 years, across 96 different strata defined by combining categories of gender, age, income, and country of birth. The stratified analysis evidenced considerable risk heterogeneity, with prevalence values ranging from 0.03% in high income immigrant women aged 50-59, to 6.18% in middle income immigrant boys aged 10-14. Our study questions the established idea that behavioural difficulties conceptualized as ADHD should be primarily perceived as a neurological abnormality. Rather, our findings suggest that there is a strong sociological component behind how some individuals become impaired and subject to medicalization.
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| 10. |
- Khalaf, Kani, et al.
(författare)
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Geographical and sociodemographic differences in discontinuation of medication for chronic obstructive pulmonary disease – a cross-classified multilevel analysis of individual heterogeneity and discriminatory accuracy (MAIHDA)
- 2020
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Ingår i: Clinical Epidemiology. - 1179-1349. ; 12, s. 783-796
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Tidskriftsartikel (refereegranskat)abstract
- Background: While discontinuation of COPD maintenance medication is a known problem, the proportion of patients with discontinuation and its geographical and sociodemographic distribution are so far unknown in Sweden. Therefore, we analyse this question by applying an innovative approach called multilevel analysis of individual heterogeneity and discriminatory accuracy (MAIHDA). Patients and Methods: We analysed 49,019 patients categorized into 18 sociodemographic contexts and 21 counties of residence. All patients had a hospital COPD diagnosis and had been on inhaled maintenance medication during the 5 years before the study baseline in 2010. We defined “discontinuation” as the absolute lack of retrieval from a pharmacy of any inhaled maintenance medication during 2011. We performed a cross-classified MAIHDA and obtained the average proportion of discontinuation, as well as county and sociodemographic absolute risks, and compared them with a proposed benchmark value of 10%. We calculated the variance partition coefficient (VPC) and the area under the receiver operating characteristics curve (AUC) to quantify county and sociodemographic differences. To summarize the results, we used a framework with 15 scenarios defined by the size of the differences and the level of achievement in relation to the benchmark value. Results: Around 18% of COPD patients in Sweden discontinued maintenance medication, so the benchmark value was not achieved. There were very small county differences (VPC=0.35%, AUC=0.54). The sociodemographic differences were small (VPC=4.98%, AUC=0.57). Conclusion: Continuity of maintenance medication among COPD patients in Sweden could be improved by reducing the unjustifiably high prevalence of discontinuation. The very small county and small sociodemographic differences should motivate universal interventions across all counties and sociodemographic groups. Geographical analyses should be combined with sociodemographic analyses, and the cross-classified MAIHDA is an appropriate tool to assess health-care quality.
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