| 1. |
- Shungin, Dmitry, et al.
(författare)
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New genetic loci link adipose and insulin biology to body fat distribution.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 187-378
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Tidskriftsartikel (refereegranskat)abstract
- Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
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| 2. |
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| 3. |
- Pennells, Lisa, et al.
(författare)
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Equalization of four cardiovascular risk algorithms after systematic recalibration : individual-participant meta-analysis of 86 prospective studies
- 2019
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 40:7, s. 621-
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Tidskriftsartikel (refereegranskat)abstract
- Aims: There is debate about the optimum algorithm for cardiovascular disease (CVD) risk estimation. We conducted head-to-head comparisons of four algorithms recommended by primary prevention guidelines, before and after ‘recalibration’, a method that adapts risk algorithms to take account of differences in the risk characteristics of the populations being studied.Methods and results: Using individual-participant data on 360 737 participants without CVD at baseline in 86 prospective studies from 22 countries, we compared the Framingham risk score (FRS), Systematic COronary Risk Evaluation (SCORE), pooled cohort equations (PCE), and Reynolds risk score (RRS). We calculated measures of risk discrimination and calibration, and modelled clinical implications of initiating statin therapy in people judged to be at ‘high’ 10 year CVD risk. Original risk algorithms were recalibrated using the risk factor profile and CVD incidence of target populations. The four algorithms had similar risk discrimination. Before recalibration, FRS, SCORE, and PCE over-predicted CVD risk on average by 10%, 52%, and 41%, respectively, whereas RRS under-predicted by 10%. Original versions of algorithms classified 29–39% of individuals aged ≥40 years as high risk. By contrast, recalibration reduced this proportion to 22–24% for every algorithm. We estimated that to prevent one CVD event, it would be necessary to initiate statin therapy in 44–51 such individuals using original algorithms, in contrast to 37–39 individuals with recalibrated algorithms.Conclusion: Before recalibration, the clinical performance of four widely used CVD risk algorithms varied substantially. By contrast, simple recalibration nearly equalized their performance and improved modelled targeting of preventive action to clinical need.
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| 4. |
- Asselbergs, Folkert W., et al.
(författare)
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Large-Scale Gene-Centric Meta-analysis across 32 Studies Identifies Multiple Lipid Loci
- 2012
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297. ; 91:5, s. 823-838
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWASs) have identified many SNPs underlying variations in plasma-lipid levels. We explore whether additional loci associated with plasma-lipid phenotypes, such as high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TGs), can be identified by a dense gene-centric approach. Our meta-analysis of 32 studies in 66,240 individuals of European ancestry was based on the custom similar to 50,000 SNP genotyping array (the ITMAT-Broad-CARe array) covering similar to 2,000 candidate genes. SNP-lipid associations were replicated either in a cohort comprising an additional 24,736 samples or within the Global Lipid Genetic Consortium. We identified four, six, ten, and four unreported SNPs in established lipid genes for HDL-C, LDL-C, TC, and TGs, respectively. We also identified several lipid-related SNPs in previously unreported genes: DGAT2, HCAR2, GPIHBP1, PPARG, and FTO for HDL-C; SOCS3, APOH, SPTY2D1, BRCA2, and VLDLR for LDL-C; SOCS3, UGT1A1, BRCA2, UBE3B, FCGR2A, CHUK, and INSIG2 for TC; and SERPINF2, C4B, GCK, GATA4, INSR, and LPAL2 for TGs. The proportion of explained phenotypic variance in the subset of studies providing individual-level data was 9.9% for HDL-C, 9.5% for LDL-C, 10.3% for TC, and 8.0% for TGs. This large meta-analysis of lipid phenotypes with the use of a dense gene-centric approach identified multiple SNPs not previously described in established lipid genes and several previously unknown loci. The explained phenotypic variance from this approach was comparable to that from a meta-analysis of GWAS data, suggesting that a focused genotyping approach can further increase the understanding of heritability of plasma lipids.
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| 5. |
- Ganesh, Santhi K., et al.
(författare)
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Loci influencing blood pressure identified using a cardiovascular gene-centric array
- 2013
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 22:8, s. 1663-1678
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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.
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| 6. |
- Tragante, Vinicius, et al.
(författare)
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Gene-centric Meta-analysis in 87,736 Individuals of European Ancestry Identifies Multiple Blood-Pressure-Related Loci.
- 2014
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297. ; 94:3, s. 349-360
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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.
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| 7. |
- Koettgen, Anna, et al.
(författare)
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Genome-wide association analyses identify 18 new loci associated with serum urate concentrations
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:2, s. 145-154
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Tidskriftsartikel (refereegranskat)abstract
- Elevated serum urate concentrations can cause gout, a prevalent and painful inflammatory arthritis. By combining data from >140,000 individuals of European ancestry within the Global Urate Genetics Consortium (GUGC), we identified and replicated 28 genome-wide significant loci in association with serum urate concentrations (18 new regions in or near TRIM46, INHBB, SEMBT1, TMEM171, VEGFA, BAZ1B, PRKAG2, STC1, HNF4G, A1CF, ATXN2, UBE2Q2, IGF1R, NFAT5, MAF, HLF, ACVR1B-ACVRL1 and B3GNT4). Associations for many of the loci were of similar magnitude in individuals of non-European ancestry. We further characterized these loci for associations with gout, transcript expression and the fractional excretion of urate. Network analyses implicate the inhibins-activins signaling pathways and glucose metabolism in systemic urate control. New candidate genes for serum urate concentration highlight the importance of metabolic control of urate production and excretion, which may have implications for the treatment and prevention of gout.
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| 8. |
- de Vries, Arjen E, et al.
(författare)
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Follow-up and treatment of an instable patient with heart failure using telemonitoring and a computerised disease management system : A case report
- 2012
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Ingår i: European Journal of Cardiovascular Nursing. - London, UK : Sage Publications. - 1474-5151 .- 1873-1953. ; 11:4, s. 432-438
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Tidskriftsartikel (refereegranskat)abstract
- In the last decades, the introduction of information and communication technology (ICT) in healthcare promised an improved quality of care while reducing workload and improving cost-effectiveness. This might be realised by the use of computer guided decision support systems and telemonitoring. This case study describes the process of care of a patient with chronic heart failure, who was treated with a computerised disease management system in combination with telemonitoring. With the help of these appliances, we think we were probably able to prevent at least two readmissions for heart failure in a period of 10months. We also gained more insight into patient's behaviour with regards to compliance with the heart failure regimen at home. Frequent contact at distance and the online availability of physiological measurements at home facilitated patient tailored education and helped the patient to react adequately to symptoms of deterioration. Additionally, up-titration of heart failure medication was performed without contacting the patient at the outpatient clinic.
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| 9. |
- de Vries, Arjen E., et al.
(författare)
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Health Professionals Expectations Versus Experiences of Internet-Based Telemonitoring: Survey Among Heart Failure Clinics
- 2013
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Ingår i: Journal of Medical Internet Research. - : Journal of Medical Internet Research / Gunther Eysenbach. - 1438-8871. ; 15:1, s. 73-83
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Tidskriftsartikel (refereegranskat)abstract
- Background: Although telemonitoring is increasingly used in heart failure care, data on expectations, experiences, and organizational implications concerning telemonitoring are rarely addressed, and the optimal profile of patients who can benefit from telemonitoring has yet to be defined. less thanbrgreater than less thanbrgreater thanObjective: To assess the actual status of use of telemonitoring and to describe the expectations, experiences, and organizational aspects involved in working with telemonitoring in heart failure in the Netherlands. less thanbrgreater than less thanbrgreater thanMethods: In collaboration with the Netherlands Organization for Applied Scientific Research (TNO), a 19-item survey was sent to all outpatient heart failure clinics in the Netherlands, addressed to cardiologists and heart failure nurses working in the clinics. less thanbrgreater than less thanbrgreater thanResults: Of the 109 heart failure clinics who received a survey, 86 clinics responded (79%). In total, 31 out of 86 (36%) heart failure clinics were using telemonitoring and 12 heart failure clinics (14%) planned to use telemonitoring within one year. The number of heart failure patients receiving telemonitoring generally varied between 10 and 50; although in two clinics more than 75 patients used telemonitoring. The main goals for using telemonitoring are "monitoring physical condition", "monitoring signs of deterioration" (n=39, 91%), "monitoring treatment" (n=32, 74%), "adjusting medication" (n=24, 56%), and "educating patients" (n=33, 77%). Most patients using telemonitoring were in the New York Heart Association (NYHA) functional classes II (n=19, 61%) and III (n=27, 87%) and were offered the use of the telemonitoring system "as long as needed" or without a time limit. However, the expectations of the use of telemonitoring were not met after implementation. Eight of the 11 items about expectations versus experiences were significantly decreased (Pandlt;.001). Health care professionals experienced the most changes related to the use of telemonitoring in their work, in particular with respect to "keeping up with current development" (before 7.2, after 6.8, P=.15), "being innovative" (before 7.0, after 6.1, P=.003), and "better guideline adherence" (before 6.3, after 5.3, P=.005). Strikingly, 20 out of 31 heart failure clinics stated that they were considering using a different telemonitoring system than the system used at the time. less thanbrgreater than less thanbrgreater thanConclusions: One third of all heart failure clinics surveyed were using telemonitoring as part of their care without any transparent, predefined criteria of user requirements. Prior expectations of telemonitoring were not reflected in actual experiences, possibly leading to disappointment. (J Med Internet Res 2013;15(1):e4) doi:10.2196/jmir.2161
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| 10. |
- de Vries, Arjen E., et al.
(författare)
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Perceived barriers of heart failure nurses and cardiologists in using clinical decision support systems in the treatment of heart failure patients
- 2013
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Ingår i: BMC Medical Informatics and Decision Making. - : BioMed Central. - 1472-6947. ; 13:54
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundClinical Decision Support Systems (CDSSs) can support guideline adherence in heart failure (HF) patients. However, the use of CDSSs is limited and barriers in working with CDSSs have been described as a major obstacle. It is unknown if barriers to CDSSs are present and differ between HF nurses and cardiologists. Therefore the aims of this study are; 1. Explore the type and number of perceived barriers of HF nurses and cardiologists to use a CDSS in the treatment of HF patients. 2. Explore possible differences in perceived barriers between two groups. 3. Assess the relevance and influence of knowledge management (KM) on Responsibility/Trust (R&T) and Barriers/Threats (B&T).MethodsA questionnaire was developed including; B&T, R&T, and KM. For analyses, descriptive techniques, 2-tailed Pearson correlation tests, and multiple regression analyses were performed.ResultsThe response- rate of 220 questionnaires was 74%. Barriers were found for cardiologists and HF nurses in all the constructs. Sixty-five percent did not want to be dependent on a CDSS. Nevertheless thirty-six percent of HF nurses and 50% of cardiologists stated that a CDSS can optimize HF medication. No relationship between constructs and age; gender; years of work experience; general computer experience and email/internet were observed. In the group of HF nurses a positive correlation (r .33, P<.01) between years of using the internet and R&T was found. In both groups KM was associated with the constructs B&T (B=.55, P=<.01) and R&T (B=.50, P=<.01).ConclusionsBoth cardiologists and HF-nurses perceived barriers in working with a CDSS in all of the examined constructs. KM has a strong positive correlation with perceived barriers, indicating that increasing knowledge about CDSSs can decrease their barriers.
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