| 1. |
- de Vries, Paul S., et al.
(author)
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Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions
- 2019
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In: American Journal of Epidemiology. - : Oxford University Press. - 0002-9262 .- 1476-6256. ; 188:6, s. 1033-1054
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Journal article (peer-reviewed)abstract
- A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups. Analyses covered the period July 2014-November 2017. Genetic main effects and interaction effects were jointly assessed by means of a 2-degrees-of-freedom (df) test, and a 1-df test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P < 1 x 10(-6)) with lipid levels in stage 1 and were evaluated in stage 2, followed by combined analyses of stage 1 and stage 2. In the combined analysis of stages 1 and 2, a total of 147 independent loci were associated with lipid levels at P < 5 x 10(-8) using 2-df tests, of which 18 were novel. No genome-wide-significant associations were found testing the interaction effect alone. The novel loci included several genes (proprotein convertase subtilisin/kexin type 5 (PCSK5), vascular endothelial growth factor B (VEGFB), and apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (APOBEC1) complementation factor (A1CF)) that have a putative role in lipid metabolism on the basis of existing evidence from cellular and experimental models.
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| 2. |
- Sung, Yun Ju, et al.
(author)
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A multi-ancestry genome-wide study incorporating gene-smoking interactions identifies multiple new loci for pulse pressure and mean arterial pressure
- 2019
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In: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 28:15, s. 2615-2633
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Journal article (peer-reviewed)abstract
- Elevated blood pressure (BP), a leading cause of global morbidity and mortality, is influenced by both genetic and lifestyle factors. Cigarette smoking is one such lifestyle factor. Across five ancestries, we performed a genome-wide gene–smoking interaction study of mean arterial pressure (MAP) and pulse pressure (PP) in 129 913 individuals in stage 1 and follow-up analysis in 480 178 additional individuals in stage 2. We report here 136 loci significantly associated with MAP and/or PP. Of these, 61 were previously published through main-effect analysis of BP traits, 37 were recently reported by us for systolic BP and/or diastolic BP through gene–smoking interaction analysis and 38 were newly identified (P < 5 × 10−8, false discovery rate < 0.05). We also identified nine new signals near known loci. Of the 136 loci, 8 showed significant interaction with smoking status. They include CSMD1 previously reported for insulin resistance and BP in the spontaneously hypertensive rats. Many of the 38 new loci show biologic plausibility for a role in BP regulation. SLC26A7 encodes a chloride/bicarbonate exchanger expressed in the renal outer medullary collecting duct. AVPR1A is widely expressed, including in vascular smooth muscle cells, kidney, myocardium and brain. FHAD1 is a long non-coding RNA overexpressed in heart failure. TMEM51 was associated with contractile function in cardiomyocytes. CASP9 plays a central role in cardiomyocyte apoptosis. Identified only in African ancestry were 30 novel loci. Our findings highlight the value of multi-ancestry investigations, particularly in studies of interaction with lifestyle factors, where genomic and lifestyle differences may contribute to novel findings.
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| 3. |
- Feitosa, Mary F., et al.
(author)
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Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries
- 2018
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In: PLOS ONE. - : Public library science. - 1932-6203. ; 13:6
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Journal article (peer-reviewed)abstract
- Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in approximate to 131 K individuals across several ancestry groups yielded 3,514 SNVs (245 loci) with suggestive evidence of association (P <1.0 x 10(-5)). In Stage 2, these SNVs were tested for independent external replication in individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2,159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 x 10(-8)). For African ancestry samples, we detected 18 potentially novel BP loci (P< 5.0 x 10(-8)) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2 have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension.
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| 4. |
- Roy, Sushmita, et al.
(author)
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Identification of functional elements and regulatory circuits by Drosophila modENCODE.
- 2010
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In: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 330:6012, s. 1787-1797
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Journal article (peer-reviewed)abstract
- To gain insight into how genomic information is translated into cellular and developmental programs, the Drosophila model organism Encyclopedia of DNA Elements (modENCODE) project is comprehensively mapping transcripts, histone modifications, chromosomal proteins, transcription factors, replication proteins and intermediates, and nucleosome properties across a developmental time course and in multiple cell lines. We have generated more than 700 data sets and discovered protein-coding, noncoding, RNA regulatory, replication, and chromatin elements, more than tripling the annotated portion of the Drosophila genome. Correlated activity patterns of these elements reveal a functional regulatory network, which predicts putative new functions for genes, reveals stage- and tissue-specific regulators, and enables gene-expression prediction. Our results provide a foundation for directed experimental and computational studies in Drosophila and related species and also a model for systematic data integration toward comprehensive genomic and functional annotation.
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| 5. |
- Best, Helen A, et al.
(author)
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Continuing professional development - global perspectives : synopsis of a workshop held during the International Association of Dental Research meeting in Gothenburg, Sweden, 2003. Part 2: regulatory and accreditation systems and evidence for improving the performance of the dental team
- 2005
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In: European journal of dental education. - : Wiley. - 1396-5883 .- 1600-0579. ; 9:2, s. 66-72
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Journal article (peer-reviewed)abstract
- This paper is the second in a series of two that report on continuing professional development (CPD). Details of the informants and the methodologies used were reported in the first paper. This paper reports the data and information presented on the topics of regulatory and accrediation systems for CPD and evidence that CPD improves the performance of the oral health team. By June 2003, participation in CPD was mandatory in most of the states of the USA, all Canadian Provinces, the UK and Latvia and was likely to become mandatory in a number of other countries in the near future. A variety of accreditation systems were reported including collecting CPD points, which in some countries were weighted depending on the type of CPD activity, and re-certification examinations. Very few studies for the effectiveness of dental CPD were identified. However, in general it was con-cluded that there is little evidence for the effectiveness of CPD for the oral health team. The main recommendation from this study is that a systematic review of the effectiveness of CPD in improving the performance of the oral health team and patient based outcomes be undertaken. A range of other research questions was also identified including: how can CPD be best matched to clinicians’ needs rather than demands?
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| 6. |
- Best, Helen A, et al.
(author)
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Continuing professional development-global perspectives : synopsis of a workshop held during the International Association of Dental Research meeting in Gothenburg, Sweden, 2003. Part 1: access, funding and participation patterns
- 2005
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In: European journal of dental education. - : Wiley. - 1396-5883 .- 1600-0579. ; 9:2, s. 59-65
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Journal article (peer-reviewed)abstract
- There appears to have been little previous research interest in continuing professional development* (CPD) of dentists and the oral health team. This paper presents data and information on the following aspects of CPD in 17 countries in Asia, Australasia, Europe and North America: availiability of different types of CPD, its providers, data on uptake of CPD courses and activities, and funding of CPD. The results indicate that lectures and hand-on skills courses were held in all 17 countries but the use of the Internet to deliver CPD was by no means universal. CPD was funded from a variety of sources including universities, governments and commercial companies. However, the only universal source of funding for CPD was dentists themselves. Data on participation were available from only three countries. Research issues based on these results will be listed in a second paper.
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| 7. |
- Winning, Tracey, et al.
(author)
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Evidence-based care and the curriculum
- 2008
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In: European journal of dental education. - : Wiley. - 1396-5883 .- 1600-0579. ; 12:Suppl 1, s. 48-63
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Research review (other academic/artistic)abstract
- An evidence-based (EB) approach has been a significant driver in reforming healthcare over the past two decades. This change has extended across a broad range of health professions, including oral healthcare. A key element in achieving an EB approach to oral healthcare is educating our practitioners, both current and future. This involves providing opportunities integrated within simulated and actual clinical settings for practitioners to learn and apply the principles and processes of evidence-based oral healthcare (EBOHC). Therefore, the focus of this discussion will be on ways in which EBOHC and associated research activities can be implemented into curricula, with the aim of improving patient care. This paper will initially define the scope of EBOHC and research, what these involve, why they are important, and issues that we need to manage when implementing EBOHC. This will be followed by a discussion of factors that enable successful implementation of EBOHC and research into curricula. The paper concludes with suggestions on the future of EBOHC and research in curricula. Key recommendations related to curricula include strengthening of the culture of a scientific approach to education and oral healthcare provision; complete integration of EBOHC into the curriculum at all levels; and faculty development to implement EBOHC based on their needs and evidence of effective approaches. Key recommendations to support implementation and maintenance of EBOHC include recognition and funding for high-quality systematic reviews and development of associated methodologies relevant for global environments; building global capacity of EBOHC researchers; research into improving translation of effective interventions into education and healthcare practice, including patient-reported outcomes, safety and harms, understanding and incorporation of patient values into EB decision-making, economic evaluation research specific to oral healthcare and effective methods for changing practitioner (faculty) behaviours; and extend access to synthesized research in 'user friendly' formats and languages tailored to meet users' needs. Realizing these recommendations may help to improve access to effective healthcare as a basic human right.
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