| 51. |
- Nakao, T., et al.
(författare)
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Mendelian randomization supports bidirectional causality between telomere length and clonal hematopoiesis of indeterminate potential
- 2022
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Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 8:14
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Tidskriftsartikel (refereegranskat)abstract
- Human genetic studies support an inverse causal relationship between leukocyte telomere length (LTL) and coronary artery disease (CAD), but directionally mixed effects for LTL and diverse malignancies. Clonal hematopoiesis of indeterminate potential (CHIP), characterized by expansion of hematopoietic cells bearing leukemogenic mutations, predisposes both hematologic malignancy and CAD. TERT (which encodes telomerase reverse transcriptase) is the most significantly associated germline locus for CHIP in genome-wide association studies. Here, we investigated the relationship between CHIP, LTL, and CAD in the Trans-Omics for Precision Medicine (TOPMed) program (n = 63,302) and UK Biobank (n = 47,080). Bidirectional Mendelian randomization studies were consistent with longer genetically imputed LTL increasing propensity to develop CHIP, but CHIP then, in turn, hastens to shorten measured LTL (mLTL). We also demonstrated evidence of modest mediation between CHIP and CAD by mLTL. Our data promote an understanding of potential causal relationships across CHIP and LTL toward prevention of CAD. Copyright © 2022 The Authors, some rights reserved;
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| 52. |
- Nordsletten, AE, et al.
(författare)
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A transcultural study of hoarding disorder: Insights from the United Kingdom, Spain, Japan, and Brazil
- 2018
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Ingår i: Transcultural psychiatry. - : SAGE Publications. - 1461-7471 .- 1363-4615. ; 55:2, s. 261-285
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Tidskriftsartikel (refereegranskat)abstract
- Though problematic hoarding is believed to be a universal human behavior, investigations of clinically-defined hoarding disorder (HD) have been confined almost exclusively to Western countries. The current investigation sought to describe and directly compare the features of individuals meeting diagnostic criteria for HD across four distinct cultural settings. Participants were 82 individuals meeting DSM-5 diagnostic criteria for HD, recruited and assessed by trained clinicians at one of four project sites: London, Barcelona, Fukuoka, and Rio de Janeiro. A series of semi-structured interviews and self-report scales were administered, including assessments of socio-demographic characteristics, psychiatric comorbidity, and severity of hoarding and related features. Results indicate that the severity and core features of HD, as well as the cognitions and behaviors commonly associated with this condition, are largely stable across cultures. However, some differences in patient demographics—in particular age, marital status, and clinical expression—as well as comorbid psychiatric features also emerged. These findings confirm that HD, as defined in DSM-5, exists and presents with similar phenomenology across the studied cultures. Future, more fine-grained, research will be needed to study the features of the disorder in additional cultures (e.g., non-industrialized nations) and to evaluate the impact of these cultural aspects on the design of interventions for the disorder.
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| 53. |
- Schuermans, Art, et al.
(författare)
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Clonal haematopoiesis of indeterminate potential predicts incident cardiac arrhythmias
- 2024
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Ingår i: European Heart Journal. - 0195-668X. ; 45:10, s. 791-805
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Tidskriftsartikel (refereegranskat)abstract
- Background and Clonal haematopoiesis of indeterminate potential (CHIP), the age-related expansion of blood cells with preleukemic mutaAims tions, is associated with atherosclerotic cardiovascular disease and heart failure. This study aimed to test the association of CHIP with new-onset arrhythmias.Methods UK Biobank participants without prevalent arrhythmias were included. Co-primary study outcomes were supraventricular arrhythmias, bradyarrhythmias, and ventricular arrhythmias. Secondary outcomes were cardiac arrest, atrial fibrillation, and any arrhythmia. Associations of any CHIP [variant allele fraction (VAF) ≥ 2%], large CHIP (VAF ≥10%), and gene-specific CHIP subtypes with incident arrhythmias were evaluated using multivariable-adjusted Cox regression. Associations of CHIP with myocardial interstitial fibrosis [T1 measured using cardiac magnetic resonance (CMR)] were also tested. Results This study included 410 702 participants [CHIP: n = 13 892 (3.4%); large CHIP: n = 9191 (2.2%)]. Any and large CHIP were associated with multi-variable-adjusted hazard ratios of 1.11 [95% confidence interval (CI) 1.04–1.18; P = .001] and 1.13 (95% CI 1.05–1.22; P = .001) for supraventricular arrhythmias, 1.09 (95% CI 1.01–1.19; P = .031) and 1.13 (95% CI 1.03–1.25; P = .011) for bradyarrhythmias, and 1.16 (95% CI, 1.00–1.34; P = .049) and 1.22 (95% CI 1.03–1.45; P = .021) for ventricular arrhythmias, respectively. Associations were independent of coronary artery disease and heart failure. Associations were also heterogeneous across arrhythmia subtypes and strongest for cardiac arrest. Gene-specific analyses revealed an increased risk of arrhythmias across driver genes other than DNMT3A. Large CHIP was associated with 1.31-fold odds (95% CI 1.07–1.59; P = .009) of being in the top quintile of myocardial fibrosis by CMR. Conclusions CHIP may represent a novel risk factor for incident arrhythmias, indicating a potential target for modulation towards arrhythmia prevention and treatment.
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