| 1. |
- Wang, Anqi, et al.
(författare)
-
Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants
- 2023
-
Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 55:12, s. 2065-2074
-
Tidskriftsartikel (refereegranskat)abstract
- The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups.
|
|
| 2. |
- Conti, David, V, et al.
(författare)
-
Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction
- 2021
-
Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 53:1, s. 65-75
-
Tidskriftsartikel (refereegranskat)abstract
- Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction. A meta-analysis of genome-wide association studies across different populations highlights new risk loci and provides a genetic risk score that can stratify prostate cancer risk across ancestries.
|
|
| 3. |
- Elsik, Christine G., et al.
(författare)
-
The Genome Sequence of Taurine Cattle : A Window to Ruminant Biology and Evolution
- 2009
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 324:5926, s. 522-528
-
Tidskriftsartikel (refereegranskat)abstract
- To understand the biology and evolution of ruminants, the cattle genome was sequenced to about sevenfold coverage. The cattle genome contains a minimum of 22,000 genes, with a core set of 14,345 orthologs shared among seven mammalian species of which 1217 are absent or undetected in noneutherian (marsupial or monotreme) genomes. Cattle-specific evolutionary breakpoint regions in chromosomes have a higher density of segmental duplications, enrichment of repetitive elements, and species-specific variations in genes associated with lactation and immune responsiveness. Genes involved in metabolism are generally highly conserved, although five metabolic genes are deleted or extensively diverged from their human orthologs. The cattle genome sequence thus provides a resource for understanding mammalian evolution and accelerating livestock genetic improvement for milk and meat production.
|
|
| 4. |
- Ganesh, Santhi K., et al.
(författare)
-
Loci influencing blood pressure identified using a cardiovascular gene-centric array
- 2013
-
Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 22:8, s. 1663-1678
-
Tidskriftsartikel (refereegranskat)abstract
- Blood pressure (BP) is a heritable determinant of risk for cardiovascular disease (CVD). To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP) and pulse pressure (PP), we genotyped 50 000 single-nucleotide polymorphisms (SNPs) that capture variation in 2100 candidate genes for cardiovascular phenotypes in 61 619 individuals of European ancestry from cohort studies in the USA and Europe. We identified novel associations between rs347591 and SBP (chromosome 3p25.3, in an intron of HRH1) and between rs2169137 and DBP (chromosome1q32.1 in an intron of MDM4) and between rs2014408 and SBP (chromosome 11p15 in an intron of SOX6), previously reported to be associated with MAP. We also confirmed 10 previously known loci associated with SBP, DBP, MAP or PP (ADRB1, ATP2B1, SH2B3/ATXN2, CSK, CYP17A1, FURIN, HFE, LSP1, MTHFR, SOX6) at array-wide significance (P 2.4 10(6)). We then replicated these associations in an independent set of 65 886 individuals of European ancestry. The findings from expression QTL (eQTL) analysis showed associations of SNPs in the MDM4 region with MDM4 expression. We did not find any evidence of association of the two novel SNPs in MDM4 and HRH1 with sequelae of high BP including coronary artery disease (CAD), left ventricular hypertrophy (LVH) or stroke. In summary, we identified two novel loci associated with BP and confirmed multiple previously reported associations. Our findings extend our understanding of genes involved in BP regulation, some of which may eventually provide new targets for therapeutic intervention.
|
|
| 5. |
|
|
| 6. |
- Tragante, Vinicius, et al.
(författare)
-
Gene-centric Meta-analysis in 87,736 Individuals of European Ancestry Identifies Multiple Blood-Pressure-Related Loci.
- 2014
-
Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297. ; 94:3, s. 349-360
-
Tidskriftsartikel (refereegranskat)abstract
- Blood pressure (BP) is a heritable risk factor for cardiovascular disease. To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP), we genotyped ∼50,000 SNPs in up to 87,736 individuals of European ancestry and combined these in a meta-analysis. We replicated findings in an independent set of 68,368 individuals of European ancestry. Our analyses identified 11 previously undescribed associations in independent loci containing 31 genes including PDE1A, HLA-DQB1, CDK6, PRKAG2, VCL, H19, NUCB2, RELA, HOXC@ complex, FBN1, and NFAT5 at the Bonferroni-corrected array-wide significance threshold (p < 6 × 10(-7)) and confirmed 27 previously reported associations. Bioinformatic analysis of the 11 loci provided support for a putative role in hypertension of several genes, such as CDK6 and NUCB2. Analysis of potential pharmacological targets in databases of small molecules showed that ten of the genes are predicted to be a target for small molecules. In summary, we identified previously unknown loci associated with BP. Our findings extend our understanding of genes involved in BP regulation, which may provide new targets for therapeutic intervention or drug response stratification.
|
|
| 7. |
- Beal, Jacob, et al.
(författare)
-
Robust estimation of bacterial cell count from optical density
- 2020
-
Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
-
Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
|
|
| 8. |
- Leach, Matthew J, et al.
(författare)
-
Skills, attitudes and uptake of evidence-based practice : A cross-sectional study of chiropractors in the Swedish Chiropractic Association
- 2021
-
Ingår i: Chiropractic and Manual Therapies. - : Springer Science and Business Media LLC. - 2045-709X. ; 29:1
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Evidence-based practice (EBP) is integral to the delivery of high-quality health care. Chiropractic has been a licensed health profession in Sweden since 1989, but little is known of the uptake of EBP in this professional group. This study explored the self-reported skills, attitudes and uptake of EBP, and the enablers and barriers of EBP uptake, among licensed chiropractors in Sweden.METHODS: Licensed chiropractors (n = 172) of the Swedish Chiropractic Association (Legitimerade Kiropraktorers Riksorganisation) were invited to participate in an anonymous online questionnaire, using the Evidence-Based Practice Attitude and Utilisation Survey (EBASE) in February 2019.RESULTS: Fifty-six (33%) chiropractors completed the survey. Participants were predominantly male, aged 30-49 years, held a Master's degree, and had received their highest qualification and practiced chiropractic for over a decade. Chiropractors rated their EBP skill-level mostly in the moderate to moderate-high range. The majority of chiropractors reported positive attitudes towards EBP, with most agreeing or strongly agreeing that EBP is necessary in the practice of chiropractic, and that EBP assists in making decisions about patient care. Chiropractors reported an average level of engagement in EBP activities. All participants indicated professional literature and research findings were useful in their day-to-day chiropractic practice. The main perceived enabler of EBP uptake was internet access in the workplace, whereas the main barrier to EBP uptake was lack of clinical evidence in chiropractic.CONCLUSIONS: Participating chiropractors of the Swedish Chiropractic Association were generally favourable of EBP, though only reported modest levels of EBP-related skills and engagement in EBP activities. Our findings suggest future studies investigating interventions focussed on improving chiropractors' skills and uptake of EBP are warranted.
|
|
| 9. |
- Sundberg, Tobias, et al.
(författare)
-
Attitudes, skills and implementation of evidence-based practice : A national cross-sectional survey of licensed naprapaths in Sweden
- 2023
-
Ingår i: Chiropractic and Manual Therapies. - : Springer Science and Business Media LLC. - 2045-709X. ; 31
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Evidence-based practice (EBP) is fundamental to the delivery of high-quality, safe and effective health care. Naprapaths, manual therapy providers that specialize in the treatment of musculoskeletal pain and dysfunction, became a Swedish licensed health profession in 1994. This study investigated the attitudes, skills and implementation of EBP among licensed naprapaths in Sweden.METHODS: Licensed naprapaths (n = 950) of Svenska Naprapatförbundet (the Swedish Naprapathy Association) were invited by email to take part in this cross-sectional anonymous online study using the Evidence-Based Practice Attitude and Utilisation Survey in February 2019.RESULTS: Fourteen percent (137/950) of invited naprapaths completed the survey. There was an approximately equal gender divide among responders; most were in the mid-career age range, practiced in city areas, and had a university or college certificate/diploma as their highest qualification. The majority of naprapaths agreed or strongly agreed that EBP was necessary in the practice of naprapathy, assisted them in making care decisions, and improved the quality of patient care. Naprapaths' self-reported skills in EBP were mostly in the moderate to moderate-high range. The majority of participating naprapaths reported infrequent implementation of EBP. Perceived minor or moderate barriers to EBP uptake included a lack of colleague support for EBP and a lack of relevant resources. Access to the internet and free online databases were reported as very useful enablers to improving EBP uptake.CONCLUSIONS: The licensed naprapaths participating in this survey reported positive attitudes toward EBP, moderate levels of EBP skills, and infrequent implementation of EBP.
|
|
| 10. |
- Alvarez, Gerard, et al.
(författare)
-
A national cross-sectional survey of the attitudes, skills and use of evidence-based practice amongst Spanish osteopaths
- 2021
-
Ingår i: BMC Health Services Research. - : Springer Science and Business Media LLC. - 1472-6963. ; 21:1
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Although evidence-based practice (EBP) is largely supported across healthcare professions, its implementation in manual therapy professions such as osteopathy remains limited and debated. There is currently little knowledge of how Spanish osteopaths relate to EBP.OBJECTIVES: The main aim of this study was to investigate the attitudes, skills and use of EBP among Spanish osteopaths. A secondary aim was to identify barriers and facilitators for the adoption of EBP in the Spanish osteopathic context.METHODS: National cross-sectional survey of Spanish osteopaths registered and non-registered to an osteopathic association in Spain. Eligible participants were invited by a range of recruitment strategies including email and social media campaigns to complete the Spanish-translated Evidence-Based practice Attitude and utilization Survey (EBASE) anonymously online.RESULTS: A total of 567 osteopaths completed the survey which represents an approximate response rate of 9%. Participant's attitudes toward EBP were largely positive. Most respondents agreed or strongly agreed that EBP was necessary in the practice of osteopathy (89.6%) and that professional literature and research findings were useful to their day-to-day practice (88.9%). Levels of perceived skill in EBP were reported as low to moderate with lowest levels for items related to 'research conduct'. Except reading/reviewing professional literature and using online search engines to find practice-related literature, participant engagement in all other EBP-related activities was generally infrequent. The perceived proportion of clinical practice that was based on clinical research evidence was reported to be very small. Main barriers to EBP uptake included a lack of clinical evidence in osteopathy and insufficient skills for applying research findings. Main facilitators of EBP uptake included access to full-text articles, internet at the workplace and online databases.CONCLUSIONS: Spanish osteopaths were largely supportive of evidence-based practice, had low to moderate skills in EBP and engaged in EBP activities infrequently. Formal regulation of the profession in Spain and the inclusion of osteopathic programs into the university sector would potentially improve EBP skills and use.
|
|
