| 1. |
- Fresard, Laure, et al.
(författare)
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Identification of rare-disease genes using blood transcriptome sequencing and large control cohorts
- 2019
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Ingår i: Nature Medicine. - : NATURE PUBLISHING GROUP. - 1078-8956 .- 1546-170X. ; 25:6, s. 911-919
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Tidskriftsartikel (refereegranskat)abstract
- It is estimated that 350 million individuals worldwide suffer from rare diseases, which are predominantly caused by mutation in a single gene(1). The current molecular diagnostic rate is estimated at 50%, with whole-exome sequencing (WES) among the most successful approaches(2-5). For patients in whom WES is uninformative, RNA sequencing (RNA-seq) has shown diagnostic utility in specific tissues and diseases(6-8). This includes muscle biopsies from patients with undiagnosed rare muscle disorders(6,9), and cultured fibroblasts from patients with mitochondrial disorders(7). However, for many individuals, biopsies are not performed for clinical care, and tissues are difficult to access. We sought to assess the utility of RNA-seq from blood as a diagnostic tool for rare diseases of different pathophysiologies. We generated whole-blood RNA-seq from 94 individuals with undiagnosed rare diseases spanning 16 diverse disease categories. We developed a robust approach to compare data from these individuals with large sets of RNA-seq data for controls (n = 1,594 unrelated controls and n = 49 family members) and demonstrated the impacts of expression, splicing, gene and variant filtering strategies on disease gene identification. Across our cohort, we observed that RNA-seq yields a 7.5% diagnostic rate, and an additional 16.7% with improved candidate gene resolution.
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| 2. |
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| 3. |
- Azevedo, Flavio, et al.
(författare)
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Social and moral psychology of COVID-19 across 69 countries
- 2023
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Ingår i: Scientific Data. - : NATURE PORTFOLIO. - 2052-4463. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- The COVID-19 pandemic has affected all domains of human life, including the economic and social fabric of societies. One of the central strategies for managing public health throughout the pandemic has been through persuasive messaging and collective behaviour change. To help scholars better understand the social and moral psychology behind public health behaviour, we present a dataset comprising of 51,404 individuals from 69 countries. This dataset was collected for the International Collaboration on Social & Moral Psychology of COVID-19 project (ICSMP COVID-19). This social science survey invited participants around the world to complete a series of moral and psychological measures and public health attitudes about COVID-19 during an early phase of the COVID-19 pandemic (between April and June 2020). The survey included seven broad categories of questions: COVID-19 beliefs and compliance behaviours; identity and social attitudes; ideology; health and well-being; moral beliefs and motivation; personality traits; and demographic variables. We report both raw and cleaned data, along with all survey materials, data visualisations, and psychometric evaluations of key variables.
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| 4. |
- Van Bavel, Jay J., et al.
(författare)
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National identity predicts public health support during a global pandemic
- 2022
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Ingår i: Nature Communications. - : Nature Portfolio. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Understanding collective behaviour is an important aspect of managing the pandemic response. Here the authors show in a large global study that participants that reported identifying more strongly with their nation reported greater engagement in public health behaviours and support for public health policies in the context of the pandemic. Changing collective behaviour and supporting non-pharmaceutical interventions is an important component in mitigating virus transmission during a pandemic. In a large international collaboration (Study 1, N = 49,968 across 67 countries), we investigated self-reported factors associated with public health behaviours (e.g., spatial distancing and stricter hygiene) and endorsed public policy interventions (e.g., closing bars and restaurants) during the early stage of the COVID-19 pandemic (April-May 2020). Respondents who reported identifying more strongly with their nation consistently reported greater engagement in public health behaviours and support for public health policies. Results were similar for representative and non-representative national samples. Study 2 (N = 42 countries) conceptually replicated the central finding using aggregate indices of national identity (obtained using the World Values Survey) and a measure of actual behaviour change during the pandemic (obtained from Google mobility reports). Higher levels of national identification prior to the pandemic predicted lower mobility during the early stage of the pandemic (r = -0.40). We discuss the potential implications of links between national identity, leadership, and public health for managing COVID-19 and future pandemics.
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| 5. |
- Chung, Sharon A, et al.
(författare)
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European population substructure is associated with mucocutaneous manifestations and autoantibody production in systemic lupus erythematosus
- 2009
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Ingår i: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 60:8, s. 2448-2456
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To determine whether genetic substructure in European-derived populations is associated with specific manifestations of systemic lupus erythematosus (SLE), including mucocutaneous phenotypes, autoantibody production, and renal disease. METHODS: SLE patients of European descent (n=1,754) from 8 case collections were genotyped for >1,400 ancestry informative markers that define a north-south gradient of European substructure. Using the Structure program, each SLE patient was characterized in terms of percent Northern (versus percent Southern) European ancestry based on these genetic markers. Nonparametric methods, including tests for trend, were used to identify associations between Northern European ancestry and specific SLE manifestations. RESULTS: In multivariate analyses, increasing levels of Northern European ancestry were significantly associated with photosensitivity (Ptrend=0.0021, odds ratio for highest quartile of Northern European ancestry versus lowest quartile [ORhigh-low] 1.64, 95% confidence interval [95% CI] 1.13-2.35) and discoid rash (Ptrend=0.014, ORhigh-low 1.93, 95% CI 0.98-3.83). In contrast, increasing levels of Northern European ancestry had a protective effect against the production of anticardiolipin autoantibodies (Ptrend=1.6x10(-4), ORhigh-low 0.46, 95% CI 0.30-0.69) and anti-double-stranded DNA autoantibodies (Ptrend=0.017, ORhigh-low 0.67, 95% CI 0.46-0.96). CONCLUSION: This study demonstrates that specific SLE manifestations vary according to Northern versus Southern European ancestry. Thus, genetic ancestry may contribute to the clinical heterogeneity and variation in disease outcomes among SLE patients of European descent. Moreover, these results suggest that genetic studies of SLE subphenotypes will need to carefully address issues of population substructure based on genetic ancestry.
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| 6. |
- Gateva, Vesela, et al.
(författare)
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A large-scale replication study identifies TNIP1, PRDM1, JAZF1, UHRF1BP1 and IL10 as risk loci for systemic lupus erythematosus
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 41:11, s. 1228-1233
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies have recently identified at least 15 susceptibility loci for systemic lupus erythematosus (SLE). To confirm additional risk loci, we selected SNPs from 2,466 regions that showed nominal evidence of association to SLE (P < 0.05) in a genome-wide study and genotyped them in an independent sample of 1,963 cases and 4,329 controls. This replication effort identified five new SLE susceptibility loci (P < 5 x 10(-8)): TNIP1 (odds ratio (OR) = 1.27), PRDM1 (OR = 1.20), JAZF1 (OR = 1.20), UHRF1BP1 (OR = 1.17) and IL10 (OR = 1.19). We identified 21 additional candidate loci with P< or = 1 x 10(-5). A candidate screen of alleles previously associated with other autoimmune diseases suggested five loci (P < 1 x 10(-3)) that may contribute to SLE: IFIH1, CFB, CLEC16A, IL12B and SH2B3. These results expand the number of confirmed and candidate SLE susceptibility loci and implicate several key immunologic pathways in SLE pathogenesis.
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| 7. |
- Hom, Geoffrey, et al.
(författare)
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Association of systemic lupus erythematosus with C8orf13-BLK and ITGAM-ITGAX.
- 2008
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Ingår i: New England Journal of Medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 358:9, s. 900-909
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Systemic lupus erythematosus (SLE) is a clinically heterogeneous disease in which the risk of disease is influenced by complex genetic and environmental contributions. Alleles of HLA-DRB1, IRF5, and STAT4are established susceptibility genes; there is strong evidence for the existence of additional risk loci.METHODS: We genotyped more than 500,000 single-nucleotide polymorphisms (SNPs) in DNA samples from 1311 case subjects with SLE and 1783 control subjects; all subjects were North Americans of European descent. Genotypes from 1557 additional control subjects were obtained from public data repositories. We measured the association between the SNPs and SLE after applying strict quality-control filters to reduce technical artifacts and to correct for the presence of population stratification. Replication of the top loci was performed in 793 case subjects and 857 control subjects from Sweden.RESULTS: Genetic variation in the region upstream from the transcription initiation site of the gene encoding B lymphoid tyrosine kinase (BLK) and C8orf13 (chromosome 8p23.1) was associated with disease risk in both the U.S. and Swedish case–control series (rs13277113; odds ratio, 1.39; P=1×10−10) and also with altered levels of messenger RNA in B-cell lines. In addition, variants on chromosome 16p11.22, near the genes encoding integrin alpha M (ITGAM, or CD11b) and integrin alpha X (ITGAX), were associated with SLE in the combined sample (rs11574637; odds ratio, 1.33; P=3×10−11).
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| 8. |
- Jensen, Simon S., et al.
(författare)
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Group 1 ITI Consensus Report : The role of bone dimensions and soft tissue augmentation procedures on the stability of clinical, radiographic, and patient-reported outcomes of implant treatment
- 2023
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Ingår i: Clinical Oral Implants Research. - : John Wiley & Sons. - 0905-7161 .- 1600-0501. ; 34, s. 43-49
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The aims of Working Group 1 were to address the role (i) of the buccolingual bone dimensions after implant placement in healed alveolar ridge sites on the occurrence of biologic and aesthetic complications, and (ii) of soft tissue augmentation (STA) on the stability of clinical, radiographic, and patient-related outcomes of implant treatments.Materials and Methods: Two systematic reviews were prepared in advance of the Consensus Conference and were discussed among the participants of Group 1. Consensus statements, clinical recommendations, recommendations for future research, and reflections on patient perspectives were based on structured group discussions until consensus was reached among the entire group of experts. The statements were then presented and accepted following further discussion and modifications as required by the plenary.Results: Dimensional changes of the alveolar ridge occurred after implant placement in healed sites, and a reduction in buccal bone wall thickness (BBW) of 0.3 to 1.8 mm was observed. In healed sites with a BBW of <1.5 mm after implant placement, increased vertical bone loss, and less favorable clinical and radiographic outcomes were demonstrated. Implants with buccal dehiscence defects undergoing simultaneous guided bone regeneration, showed less vertical bone loss, and more favorable clinical and radiographic outcomes, compared to non-augmented dehiscence defects during initial healing. At healthy single implant sites, probing depths, bleeding and plaque scores, and interproximal bone levels evaluated at 1 year, remained stable for up to 5 years, with or without STA. When single implant sites were augmented with connective tissue grafts, either for soft tissue phenotype modification or buccal soft tissue dehiscence, stable levels of the soft tissue margin, and stable or even increased soft tissue thickness and/or width of keratinized mucosa could be observed from 1 to 5 years. In contrast, non-augmented sites were more prone to show apical migration of the soft tissue margin in the long-term. Favorable aesthetic and patient-reported outcomes after STA were documented to be stable from 1 to 5 years.Results: Dimensional changes of the alveolar ridge occurred after implant placement in healed sites, and a reduction in buccal bone wall thickness (BBW) of 0.3 to 1.8 mm was observed. In healed sites with a BBW of <1.5 mm after implant placement, increased vertical bone loss, and less favorable clinical and radiographic outcomes were demonstrated. Implants with buccal dehiscence defects undergoing simultaneous guided bone regeneration, showed less vertical bone loss, and more favorable clinical and radiographic outcomes, compared to non-augmented dehiscence defects during initial healing. At healthy single implant sites, probing depths, bleeding and plaque scores, and interproximal bone levels evaluated at 1 year, remained stable for up to 5 years, with or without STA. When single implant sites were augmented with connective tissue grafts, either for soft tissue phenotype modification or buccal soft tissue dehiscence, stable levels of the soft tissue margin, and stable or even increased soft tissue thickness and/or width of keratinized mucosa could be observed from 1 to 5 years. In contrast, non-augmented sites were more prone to show apical migration of the soft tissue margin in the long-term. Favorable aesthetic and patient-reported outcomes after STA were documented to be stable from 1 to 5 years. Conclusions: It is concluded that dimensional changes of the alveolar ridge occur after implant placement in healed sites and that sites with a thin BBW after implant placement are prone to exhibit less favorable clinical and radiographic outcomes. In addition, it is concluded that STA can provide stable clinical, radiographic, aesthetic, and patient-reported outcomes in the medium and long-term.
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| 9. |
- Kurdi-Haidar, B, et al.
(författare)
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Isolation of the ATP-binding human homolog of the arsA component of the bacterial arsenite transporter.
- 1996
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Ingår i: Genomics. - : Elsevier BV. - 0888-7543. ; 36:3, s. 486-91
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Tidskriftsartikel (refereegranskat)abstract
- Arsenite resistance in bacteria is mediated by an efflux pump composed of the arsA and arsB gene products. We have isolated the human homolog of the bacterial arsA (hARSA-I), a member of the ATPase superfamily with no transmembrane domain. Southern and Northern analyses indicated the presence of two cross-hybridizing genes in the human genome and expression of hARSA-I in many tissues. A rabbit antiserum raised against a glutathione-S-transferase (GST)/hARSA-I fusion protein identified two cross-reacting proteins of 37 and 42 kDa by Western analysis in two different human cell lines. Overexpression of hARSA-I in the embryonal human kidney 293 cell line was accompanied by overproduction of the 37-kDa protein Biochemical analysis using the GST/hARSA-I fusion protein indicated that hARSA-I is an ATPase analogous to the bacterial ArsA. Thus, hARSA-I is a new eukaryotic member of a highly conserved ATP-binding superfamily of proteins.
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| 10. |
- Rietveld, Anne M., et al.
(författare)
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A Community of Practice for Gender-Transformative Research Methodologies
- 2022
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Rapport (refereegranskat)abstract
- The Community of Practice on Gender-Transformative Research Methodologies (GTRM-CoP) builds on work conducted by international gender researchers at CGIAR and partner organizations. The community of practice is committed to gender-transformative change processes; and aims to co-create socially just and gender-equitable futures in food, land and water systems. The GTRM-CoP aims to promote the transformative ambitions of CGIAR, its partners, and interested organizations and individuals, by creating safe spaces for innovating, sharing and scaling gender-transformative research methodologies. The community of practice is part of the CGIAR GENDER Impact Platform and housed under the Methods module of the Platform. A Community of Practice (CoP) is an ideal mechanism for promoting rapid, interactive and creative learning. Four initial topic groups have been identified to begin knowledge exchange and co-creation: gender-equitable masculinities, intersectionality, transformative research processes and data, and mobilizing GENNOVATE data and tools. The GTRM-CoP aims to accelerate learning and action that fosters gender-transformative change in food, land and water systems, through the interactions within and between the topic groups, following a set of principles and values and in a spirit of humility and learning. These lessons will be available to others within CGIAR and beyond as part of a global movement toward gender equity and achieving Gender Equality (SDG 5) and Reduced Inequalities (SDG 10).
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