| 1. |
- Lumbers, R. T., et al.
(författare)
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The genomics of heart failure: design and rationale of the HERMES consortium
- 2021
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Ingår i: Esc Heart Failure. - : Wiley. - 2055-5822. ; 8:6, s. 5531-5541
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Tidskriftsartikel (refereegranskat)abstract
- Aims The HERMES (HEart failure Molecular Epidemiology for Therapeutic targets) consortium aims to identify the genomic and molecular basis of heart failure. Methods and results The consortium currently includes 51 studies from 11 countries, including 68 157 heart failure cases and 949 888 controls, with data on heart failure events and prognosis. All studies collected biological samples and performed genome-wide genotyping of common genetic variants. The enrolment of subjects into participating studies ranged from 1948 to the present day, and the median follow-up following heart failure diagnosis ranged from 2 to 116 months. Forty-nine of 51 individual studies enrolled participants of both sexes; in these studies, participants with heart failure were predominantly male (34-90%). The mean age at diagnosis or ascertainment across all studies ranged from 54 to 84 years. Based on the aggregate sample, we estimated 80% power to genetic variant associations with risk of heart failure with an odds ratio of >1.10 for common variants (allele frequency > 0.05) and >1.20 for low-frequency variants (allele frequency 0.01-0.05) at P < 5 x 10(-8) under an additive genetic model. Conclusions HERMES is a global collaboration aiming to (i) identify the genetic determinants of heart failure; (ii) generate insights into the causal pathways leading to heart failure and enable genetic approaches to target prioritization; and (iii) develop genomic tools for disease stratification and risk prediction.
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| 2. |
- Shah, S, et al.
(författare)
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Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure
- 2020
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 163-
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Tidskriftsartikel (refereegranskat)abstract
- Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies.
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| 3. |
- Dai, Qile, et al.
(författare)
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OTTERS: a powerful TWAS framework leveraging summary-level reference data
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Most existing TWAS tools require individual-level eQTL reference data and thus are not applicable to summary-level reference eQTL datasets. The development of TWAS methods that can harness summary-level reference data is valuable to enable TWAS in broader settings and enhance power due to increased reference sample size. Thus, we develop a TWAS framework called OTTERS (Omnibus Transcriptome Test using Expression Reference Summary data) that adapts multiple polygenic risk score (PRS) methods to estimate eQTL weights from summary-level eQTL reference data and conducts an omnibus TWAS. We show that OTTERS is a practical and powerful TWAS tool by both simulations and application studies.
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| 4. |
- Becker, Joel, et al.
(författare)
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Resource profile and user guide of the Polygenic Index Repository
- 2021
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Ingår i: Nature Human Behaviour. - : Nature Research (part of Springer Nature). - 2397-3374. ; 51:6, s. 694-695
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Tidskriftsartikel (refereegranskat)abstract
- Polygenic indexes (PGIs) are DNA-based predictors. Their value for research in many scientific disciplines is growing rapidly. As a resource for researchers, we used a consistent methodology to construct PGIs for 47 phenotypes in 11 datasets. To maximize the PGIs’ prediction accuracies, we constructed them using genome-wide association studies—some not previously published—from multiple data sources, including 23andMe and UK Biobank. We present a theoretical framework to help interpret analyses involving PGIs. A key insight is that a PGI can be understood as an unbiased but noisy measure of a latent variable we call the ‘additive SNP factor’. Regressions in which the true regressor is this factor but the PGI is used as its proxy therefore suffer from errors-in-variables bias. We derive an estimator that corrects for the bias, illustrate the correction, and make a Python tool for implementing it publicly available. © 2021, The Author(s), under exclusive licence to Springer Nature Limited.
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| 5. |
- Ekberg, EwaCarin, et al.
(författare)
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Diagnostic Criteria for Temporomandibular Disorders - INfORM recommendations : Comprehensive and short-form adaptations for adolescents.
- 2023
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Ingår i: Journal of Oral Rehabilitation. - : John Wiley & Sons. - 1365-2842. ; 50:11, s. 1167-1180
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) for use in adults is in use worldwide. Until now, no version of this instrument for use in adolescents has been proposed.OBJECTIVE: To present comprehensive and short-form adaptations of the adult version of DC/TMD that are appropriate for use with adolescents in clinical and research settings.METHODS: International experts in TMDs and experts in pain psychology participated in a Delphi process to identify ways of adapting the DC/TMD protocol for physical and psychosocial assessment of adolescents.RESULTS: The proposed adaptation defines adolescence as ages 10-19 years. Changes in the physical diagnosis (Axis I) include (i) adapting the language of the Demographics and the Symptom Questionnaires to be developmentally appropriate for adolescents, (ii) adding two general health questionnaires, one for the adolescent patient and one for their caregivers, and (iii) replacing the TMD Pain Screener with the 3Q/TMD questionnaire. Changes in the psychosocial assessment (Axis II) include (i) adapting the language of the Graded Chronic Pain Scale to be developmentally appropriate for adolescents, (ii) adding anxiety and depression assessment that have been validated for adolescents, and (iii) adding three constructs (stress, catastrophizing and sleep disorders) to assess psychosocial functioning in adolescents.CONCLUSION: The recommended DC/TMD, including Axis I and Axis II for adolescents, is appropriate to use in clinical and research settings. This adapted first version for adolescents includes changes in Axis I and Axis II requiring reliability and validity testing in international settings. Official translations of the comprehensive and short-form to different languages according to INfORM requirements will enable a worldwide dissemination and implementation.
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| 6. |
- Enbody, Erik D., et al.
(författare)
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Community-wide genome sequencing reveals 30 years of Darwin's finch evolution
- 2023
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 381:6665, s. 1427-
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Tidskriftsartikel (refereegranskat)abstract
- A fundamental goal in evolutionary biology is to understand the genetic architecture of adaptive traits. Using whole-genome data of 3955 of Darwin's finches on the Galapagos Island of Daphne Major, we identified six loci of large effect that explain 45% of the variation in the highly heritable beak size of Geospiza fortis, a key ecological trait. The major locus is a supergene comprising four genes. Abrupt changes in allele frequencies at the loci accompanied a strong change in beak size caused by natural selection during a drought. A gradual change in Geospiza scandens occurred across 30 years as a result of introgressive hybridization with G. fortis. This study shows how a few loci with large effect on a fitness-related trait contribute to the genetic potential for rapid adaptive radiation.
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| 7. |
- Rongo, Roberto, et al.
(författare)
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Diagnostic criteria for temporomandibular disorders in children and adolescents: An international Delphi study-Part 2-Development of Axis II
- 2022
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Ingår i: Journal of Oral Rehabilitation. - : WILEY. - 1365-2842 .- 0305-182X. ; 49:5, s. 541-552
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Tidskriftsartikel (refereegranskat)abstract
- Background Unlike the psychosocial assessment established for adults in the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD), a standardised psychosocial assessment for children and adolescents with TMD complaints has not yet been established. Objectives To develop a new standardised instrument set to assess the psychosocial functioning in children and adolescents by adapting the psychosocial status and pain-related disability (Axis II) of the adult DC/TMD and by including new instruments. Methods A modified Delphi method was used to survey 23 international TMD experts and four international experts in pain-related psychological factors for consensus regarding assessment tools for psychosocial functioning and pain-related disability in children and adolescents. The TMD experts reviewed 29 Axis II statements at round 1, 13 at round 2 and 2 at round 3. Agreement was set at 80% for first-round consensus level and 70% for each of the second and third rounds. The psychological experts completed a complementary Delphi survey to reach a consensus on tools to use to assess more complex psychological domains in children and adolescents. For the psychological experts, the first round included 10 open-ended questions on preferred screening tools for depression, anxiety, catastrophising, sleep problems and stress in children (ages 6-9 years old) and adolescents (ages 10-19 years old) as well as on other domains suggested for investigation. In the second round, the psychological experts received a 9-item questionnaire to prioritise the suggested instruments from most to least recommended. Results The TMD experts, after three Delphi rounds, reached consensus on the changes of DC/TMD to create a form to evaluate Axis II in children and adolescents with TMD complaints. The psychological experts added tools to assess depression and anxiety, sleep disorders, catastrophising, stress and resilience. Conclusion Through international expert consensus, this study adapted Axis II of the adult DC/TMD to assess psychosocial functioning and pain-related disability in children and adolescents. The adapted Axis II protocols will be validated in the target populations.
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| 8. |
- Durham, Justin, et al.
(författare)
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Constructing the brief diagnostic criteria for temporomandibular disorders (bDC/TMD) for field testing
- 2024
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Ingår i: Journal of Oral Rehabilitation. - : John Wiley & Sons. - 1365-2842. ; 51:5, s. 785-794
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Tidskriftsartikel (refereegranskat)abstract
- Background: Despite advances in temporomandibular disorders' (TMDs) diagnosis, the diagnostic process continues to be problematic in non-specialist settings.Objective: To complete a Delphi process to shorten the Diagnostic Criteria for TMD (DC/TMD) to a brief DC/TMD (bDC/TMD) for expedient clinical diagnosis and initial management.Methods: An international Delphi panel was created with 23 clinicians representing major specialities, general dentistry and related fields. The process comprised a full day workshop, seven virtual meetings, six rounds of electronic discussion and finally an open consultation at a virtual international symposium.Results: Within the physical axis (Axis 1), the self-report Symptom Questionnaire of the DC/TMD did not require shortening from 14 items for the bDC/TMD. The compulsory use of the TMD pain screener was removed reducing the total number of Axis 1 items by 18%. The DC/TMD Axis 1 10-section examination protocol (25 movements, up to 12 sets of bilateral palpations) was reduced to four sections in the bDC/TMD protocol involving three movements and three sets of palpations. Axis I then resulted in two groups of diagnoses: painful TMD (inclusive of secondary headache), and common joint-related TMD with functional implications. The psychosocial axis (Axis 2) was shortened to an ultra-brief 11 item assessment.Conclusion: The bDC/TMD represents a substantially reduced and likely expedited method to establish (grouping) diagnoses in TMDs. This may provide greater utility for settings requiring less granular diagnoses for the implementation of initial treatment, for example non-specialist general dental practice.
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| 9. |
- Lobbezoo, Frank, et al.
(författare)
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A century of bruxism research in top-ranking medical journals
- 2024
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Ingår i: Cephalalgia Reports. - : Sage Publications. - 2515-8163 .- 2515-8163. ; 7
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Forskningsöversikt (refereegranskat)abstract
- Background: Bruxism is a jaw-muscle activity characterized by teeth grinding and clenching. While many of its negative consequences (e.g., jaw-muscle pain, tooth fractures) are of particular interest to dentists, new insights underline the need for physicians to be knowledgeable about bruxism. In order to facilitate transfer of knowledge across disciplines, our objective was to assess what top-ranking medical journals have published on bruxism. Besides, we tested the insights described there against current science regarding the definition, assessment, epidemiology, etiology, consequences, comorbidities, and management of bruxism.Results: In the past century, the four top-ranking medical journals have provided their readership with various bits and pieces of information on bruxism. While some of these insights have withstood the test of time, others are somewhat outdated. Further, the identified publications provide an incomplete picture of what physicians should know. The present article helps reduce this knowledge gap.Conclusion: The role of the physician with regard to bruxism focuses mainly on its assessment and management, while insight into risk factors and comorbid conditions of bruxism is essential to high-level patient care. It is hoped that this article will contribute to improve the long-needed interdisciplinary collaboration between physicians and dentists regarding the assessment and management of bruxing patients.
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| 10. |
- Nilsson, Ing-Marie, et al.
(författare)
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Diagnostic Criteria for Temporomandibular Disorders - INfORM recommendations : Comprehensive and short-form adaptations for children
- 2023
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Ingår i: Journal of Oral Rehabilitation. - : John Wiley & Sons. - 1365-2842 .- 0305-182X. ; 50:2, s. 99-112
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) are used worldwide in adults. Until now, no adaptation for use in children has been proposed.OBJECTIVE: To present comprehensive and short-form adaptations of Axis I and II of the DC/TMD for adults that are appropriate for use with children in clinical and research settings.METHODS: Global Delphi studies with experts in TMDs and in pain psychology identified ways of adapting the DC/TMD for children.RESULTS: The proposed adaptation is suitable for children aged 6-9 years. Proposed changes in Axis I include (i) adapting the language of the Demographics and the Symptom Questionnaires to be developmentally appropriate for children, (ii) adding a general health questionnaire for children and one for their parents, (iii) replacing the TMD Pain Screener with the 3Q/TMD questionnaire, and (iv) modifying the clinical examination protocol. Proposed changes in Axis II include (i) for the Graded Chronic Pain Scale, to be developmentally appropriate for children, and (ii) adding anxiety and depression assessments that have been validated in children, and (iii) adding three constructs (stress, catastrophizing, and sleep disorders) to assess psychosocial functioning in children.CONCLUSION: The recommended DC/TMD, including Axis I and Axis II, for children aged 6-9 years, is appropriate for use in clinical and research settings. This adapted first version for children includes changes in Axis I and Axis II changes requiring reliability and validity testing in international settings. Official translations to different languages according to INfORM requirements will enable a worldwide dissemination and implementation.
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| 11. |
- Okbay, Aysu, et al.
(författare)
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Polygenic prediction of educational attainment within and between families from genome-wide association analyses in 3 million individuals.
- 2022
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 54:4, s. 437-449
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Tidskriftsartikel (refereegranskat)abstract
- We conduct a genome-wide association study (GWAS) of educational attainment (EA) in a sample of ~3 million individuals and identify 3,952 approximately uncorrelated genome-wide-significant single-nucleotide polymorphisms (SNPs). A genome-wide polygenic predictor, or polygenic index (PGI), explains 12-16% of EA variance and contributes to risk prediction for ten diseases. Direct effects (i.e., controlling for parental PGIs) explain roughly half the PGI's magnitude of association with EA and other phenotypes. The correlation between mate-pair PGIs is far too large to be consistent with phenotypic assortment alone, implying additional assortment on PGI-associated factors. In an additional GWAS of dominance deviations from the additive model, we identify no genome-wide-significant SNPs, and a separate X-chromosome additive GWAS identifies 57.
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| 12. |
- Patxot, Marion, et al.
(författare)
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Probabilistic inference of the genetic architecture underlying functional enrichment of complex traits
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- We develop a Bayesian model (BayesRR-RC) that provides robust SNP-heritability estimation, an alternative to marker discovery, and accurate genomic prediction, taking 22 seconds per iteration to estimate 8.4 million SNP-effects and 78 SNP-heritability parameters in the UK Biobank. We find that only ≤10% of the genetic variation captured for height, body mass index, cardiovascular disease, and type 2 diabetes is attributable to proximal regulatory regions within 10kb upstream of genes, while 12-25% is attributed to coding regions, 32–44% to introns, and 22-28% to distal 10-500kb upstream regions. Up to 24% of all cis and coding regions of each chromosome are associated with each trait, with over 3,100 independent exonic and intronic regions and over 5,400 independent regulatory regions having ≥95% probability of contributing ≥0.001% to the genetic variance of these four traits. Our open-source software (GMRM) provides a scalable alternative to current approaches for biobank data.
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| 13. |
- Rongo, Roberto, et al.
(författare)
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Diagnostic criteria for temporomandibular disorders (DC/TMD) for children and adolescents : An international Delphi study—Part 1‐Development of Axis I
- 2021
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Ingår i: Journal of Oral Rehabilitation. - : John Wiley & Sons. - 1365-2842 .- 0305-182X. ; 48:7, s. 836-845
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To develop new instruments and to adapt the diagnostic criteria for temporomandibular disorders (DC/TMD) for the evaluation of TMD in children and adolescents.METHOD: A modified Delphi method was used to seek international consensus among TMD experts. Fourteen clinicians and researchers in the field of orofacial pain and TMD worldwide were invited to participate in a workshop initiated by the International Network for Orofacial Pain and Related Disorders Methodology (INfORM scientific network) at the General Session of the International Association for Dental Research (IADR, London 2018), as the first step in the Delphi process. Participants discussed the protocols required to make physical diagnoses included in the Axis I of the DC/TMD. Thereafter, nine experts in the field were added, and the first Delphi round was created. This survey included 60 statements for Axis I, and the experts were asked to respond to each statement on a five-item Likert scale ranging from "Strongly disagree" to "Strongly agree". Consensus level was set at 80% agreement for the first round, and at 70% for the next.RESULTS: After three rounds of the Delphi process, a consensus among TMD experts was achieved and two adapted DC/TMD protocols for Axis I physical diagnoses for children and adolescents were developed.CONCLUSION: Through international consensus among TMD experts, this study adapted the Axis I of the DC/TMD for use in evaluating TMD in children and adolescents.
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