| 1. |
- Thompson, Paul M., et al.
(författare)
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The ENIGMA Consortium : large-scale collaborative analyses of neuroimaging and genetic data
- 2014
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Ingår i: BRAIN IMAGING BEHAV. - : Springer Science and Business Media LLC. - 1931-7557 .- 1931-7565. ; 8:2, s. 153-182
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Tidskriftsartikel (refereegranskat)abstract
- The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way.
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| 2. |
- van de Vegte, Yordi, et al.
(författare)
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Genetic insights into resting heart rate and its role in cardiovascular disease
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- The genetics and clinical consequences of resting heart rate (RHR) remain incompletely understood. Here, the authors discover new genetic variants associated with RHR and find that higher genetically predicted RHR decreases risk of atrial fibrillation and ischemic stroke. Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associated genetic variants and to obtain further insights in resting heart rate biology and its clinical consequences. A genome-wide meta-analysis of 100 studies in up to 835,465 individuals reveals 493 independent genetic variants in 352 loci, including 68 genetic variants outside previously identified resting heart rate associated loci. We prioritize 670 genes and in silico annotations point to their enrichment in cardiomyocytes and provide insights in their ECG signature. Two-sample Mendelian randomization analyses indicate that higher genetically predicted resting heart rate increases risk of dilated cardiomyopathy, but decreases risk of developing atrial fibrillation, ischemic stroke, and cardio-embolic stroke. We do not find evidence for a linear or non-linear genetic association between resting heart rate and all-cause mortality in contrast to our previous Mendelian randomization study. Systematic alteration of key differences between the current and previous Mendelian randomization study indicates that the most likely cause of the discrepancy between these studies arises from false positive findings in previous one-sample MR analyses caused by weak-instrument bias at lower P-value thresholds. The results extend our understanding of resting heart rate biology and give additional insights in its role in cardiovascular disease development.
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| 3. |
- Marouli, Eirini, et al.
(författare)
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Rare and low-frequency coding variants alter human adult height
- 2017
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 542:7640, s. 186-190
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Tidskriftsartikel (refereegranskat)abstract
- Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
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| 4. |
- Coresh, Josef, et al.
(författare)
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Decline in estimated glomerular filtration rate and subsequent risk of end-stage renal disease and mortality
- 2014
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Ingår i: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 311:24, s. 2518-2531
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: The established chronic kidney disease (CKD) progression end point of end-stage renal disease (ESRD) or a doubling of serum creatinine concentration (corresponding to a change in estimated glomerular filtration rate [GFR] of −57% or greater) is a late event.OBJECTIVE: To characterize the association of decline in estimated GFR with subsequent progression to ESRD with implications for using lesser declines in estimated GFR as potential alternative end points for CKD progression. Because most people with CKD die before reaching ESRD, mortality risk also was investigated.DATA SOURCES AND STUDY SELECTION: Individual meta-analysis of 1.7 million participants with 12,344 ESRD events and 223,944 deaths from 35 cohorts in the CKD Prognosis Consortium with a repeated measure of serum creatinine concentration over 1 to 3 years and outcome data.DATA EXTRACTION AND SYNTHESIS: Transfer of individual participant data or standardized analysis of outputs for random-effects meta-analysis conducted between July 2012 and September 2013, with baseline estimated GFR values collected from 1975 through 2012.MAIN OUTCOMES AND MEASURES: End-stage renal disease (initiation of dialysis or transplantation) or all-cause mortality risk related to percentage change in estimated GFR over 2 years, adjusted for potential confounders and first estimated GFR.RESULTS: The adjusted hazard ratios (HRs) of ESRD and mortality were higher with larger estimated GFR decline. Among participants with baseline estimated GFR of less than 60 mL/min/1.73 m2, the adjusted HRs for ESRD were 32.1 (95% CI, 22.3-46.3) for changes of −57% in estimated GFR and 5.4 (95% CI, 4.5-6.4) for changes of −30%. However, changes of −30% or greater (6.9% [95% CI, 6.4%-7.4%] of the entire consortium) were more common than changes of −57% (0.79% [95% CI, 0.52%-1.06%]). This association was strong and consistent across the length of the baseline period (1 to 3 years), baseline estimated GFR, age, diabetes status, or albuminuria. Average adjusted 10-year risk of ESRD (in patients with a baseline estimated GFR of 35 mL/min/1.73 m2) was 99% (95% CI, 95%-100%) for estimated GFR change of −57%, was 83% (95% CI, 71%-93%) for estimated GFR change of −40%, and was 64% (95% CI, 52%-77%) for estimated GFR change of −30% vs 18% (95% CI, 15%-22%) for estimated GFR change of 0%. Corresponding mortality risks were 77% (95% CI, 71%-82%), 60% (95% CI, 56%-63%), and 50% (95% CI, 47%-52%) vs 32% (95% CI, 31%-33%), showing a similar but weaker pattern.CONCLUSIONS AND RELEVANCE: Declines in estimated GFR smaller than a doubling of serum creatinine concentration occurred more commonly and were strongly and consistently associated with the risk of ESRD and mortality, supporting consideration of lesser declines in estimated GFR (such as a 30% reduction over 2 years) as an alternative end point for CKD progression.
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| 5. |
- Beal, Jacob, et al.
(författare)
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Robust estimation of bacterial cell count from optical density
- 2020
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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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.
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| 6. |
- Bhat, Saiuj, et al.
(författare)
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A Systematic Review of the Sources of Dietary Salt Around the World.
- 2020
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Ingår i: Advances in nutrition (Bethesda, Md.). - : Elsevier BV. - 2156-5376 .- 2161-8313. ; 11:3, s. 677-686
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Tidskriftsartikel (refereegranskat)abstract
- Excess salt intake contributes to hypertension and increased cardiovascular disease risk. Efforts to implement effective salt-reduction strategies require accurate data on the sources of salt consumption. We therefore performed a systematic review to identify the sources of dietary salt around the world. We systematically searched peer-reviewed and gray literature databases for studies that quantified discretionary (salt added during cooking or at the table) and nondiscretionary sources of salt and those that provided information about the food groups contributing to dietary salt intake. Exploratory linear regression analysis was also conducted to assess whether the proportion of discretionary salt intake is related to the gross domestic product (GDP) per capita of a country. We identified 80 studies conducted in 34 countries between 1975 and 2018. The majority (n = 44, 55%) collected data on dietary salt sources within the past 10 y and were deemed to have a low or moderate risk of bias (n = 75, 94%). Thirty-two (40%) studies were judged to be nationally representative. Populations in Brazil, China, Costa Rica, Guatemala, India, Japan, Mozambique, and Romania received more than half of their daily salt intake from discretionary sources. A significant inverse correlation between discretionary salt intake and a country's per capita GDP was observed (P < 0.0001), such that for every $10,000 increase in per capita GDP, the amount of salt obtained from discretionary sources was lower by 8.7% (95% CI: 5.1%, 12%). Bread products, cereal and grains, meat products, and dairy products were the major contributors to dietary salt intake in most populations. There is marked variation in discretionary salt use around the world that is highly correlated with the level of economic development. Our findings have important implications for the type of salt-reduction strategy likely to be effective in a country.
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| 7. |
- Greer, Raquel C, et al.
(författare)
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Potassium-Enriched Salt Substitutes as a Means to Lower Blood Pressure : Benefits and Risks.
- 2020
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Ingår i: Hypertension. - 0194-911X .- 1524-4563. ; 75:2, s. 266-274
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Tidskriftsartikel (refereegranskat)abstract
- Use of salt substitutes containing potassium chloride is a potential strategy to reduce sodium intake, increase potassium intake, and thereby lower blood pressure and prevent the adverse consequences of high blood pressure. In this review, we describe the rationale for using potassium-enriched salt substitutes, summarize current evidence on the benefits and risks of potassium-enriched salt substitutes and discuss the implications of using potassium-enriched salt substitutes as a strategy to lower blood pressure. A benefit of salt substitutes that contain potassium chloride is the expected reduction in dietary sodium intake at the population level because of reformulation of manufactured foods or replacement of sodium chloride added to food during home cooking or at the dining table. There is empirical evidence that replacement of sodium chloride with potassium-enriched salt substitutes lowers systolic and diastolic blood pressure (average net Δ [95% CI] in mm Hg: -5.58 [-7.08 to -4.09] and -2.88 [-3.93 to -1.83], respectively). The risks of potassium-enriched salt substitutes include a possible increased risk of hyperkalemia and its principal adverse consequences: arrhythmias and sudden cardiac death, especially in people with conditions that impair potassium excretion such as chronic kidney disease. There is insufficient evidence regarding the effects of potassium-enriched salt substitutes on the occurrence of hyperkalemia. There is a need for additional empirical research on the effect of increasing dietary potassium and potassium-enriched salt substitutes on serum potassium levels and the risk of hyperkalemia, as well as for robust estimation of the population-wide impact of replacing sodium chloride with potassium-enriched salt substitutes.
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| 8. |
- Hussain, Tasfia, et al.
(författare)
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Quality assessment of consumer-facing websites on sodium reduction
- 2022
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Ingår i: The Journal of Clinical Hypertension. - : Wiley-Blackwell. - 1524-6175 .- 1751-7176. ; 24:10, s. 1285-1292
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this paper is to evaluate the quality of information and guidance on dietary sodium reduction available on consumer-facing websites. Google Trends was used to identify the five most-used search terms related to dietary sodium reduction. For each term, websites on the first two pages were collected (n = 18-20). Of 93 websites collected, 24 were excluded due to defective links, duplicate websites, or not being consumer-focused. The remaining 69 websites were evaluated using a novel instrument, JHU-SALT, that includes 14 questions on topics related to salt reduction. The questions are grouped into three domains ("information," "guidance," and "accuracy"). For each question, websites were scored using a 3-step ordinal scale ("topic not addressed," "topic somewhat addressed," or "topic addressed adequately"). Only three of 14 JHU-SALT questions were addressed adequately by a majority of websites. Many websites provided information on the adverse health effects of a high sodium diet (74%, n = 51) or mentioned intake recommendations (64%, n = 44). Information on fundamental concepts was largely missing. The majority of websites (80%, n = 55) provided information on lifestyle strategies to reduce blood pressure, but most did not provide guidance to help implement those strategies. While missing information was common, misinformation was uncommon. The DISCERN questionnaire was utilized as well. Consumers seeking information and guidance on dietary sodium reduction will find that most available websites provide accurate but limited information, and insufficient guidance on how to lower sodium intake. Websites that provide both relevant information and guidance are needed to help consumers effectively reduce dietary sodium.
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| 9. |
- Johnson Curtis, Christine, et al.
(författare)
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Considerations for modelling a broad food tax in the Philippines and other low-income and middle-income countries
- 2023
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Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 8:SUPPL_8
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Tidskriftsartikel (refereegranskat)abstract
- Fiscal policies to improve diet are a promising strategy to address the increasing burden of non-communicable disease, the leading cause of death globally. Sugar-sweetened beverage taxes are the most implemented type of fiscal policy to improve diet. Yet taxes on food, if appropriately structured and applied across the food supply, may support a larger population-level shift towards a healthier diet. Designing these policies and guiding them through the legislative process requires evidence. Equity-oriented cost-effectiveness analyses that estimate the distribution of potential health and economic gains can provide this critical evidence. Taxes on less healthy foods are rarely modelled in low-income and middle-income countries.We describe considerations for modelling the effect of a food tax, which can provide guidance for food tax policy design. This includes describing issues related to the availability, reliability and level of detail of national data on dietary habits, the nutrient content of foods and food prices; the structure of the nutrient profile model; type of tax; tax rate; pass-through rate and price elasticity. Using the Philippines as an example, we discuss considerations for using existing data to model the potential effect of a tax, while also taking into account the political and food policy context. In this way, we provide a modelling framework that can help guide policy-makers and advocates in designing a food policy to improve the health and well-being of future generations in the Philippines and elsewhere.
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| 10. |
- Marklund, Matti, et al.
(författare)
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Estimated Benefits and Risks of Using a Reduced-Sodium, Potassium-Enriched Salt Substitute in India : A Modeling Study
- 2022
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Ingår i: Hypertension. - : Lippincott Williams & Wilkins. - 0194-911X .- 1524-4563. ; 79:10, s. 2188-2198
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Tidskriftsartikel (refereegranskat)abstract
- Background: Salt substitution (ie, replacement of table and cooking salt with potassium-enriched salt substitutes) is a promising strategy to reduce blood pressure and prevent cardiovascular disease, particularly in countries like India where there is high sodium intake, mainly from discretionary salt, and low potassium intake. Life-threatening hyperkalemia from increased potassium intake is a postulated concern for individuals with chronic kidney disease.Methods: We used comparative risk assessment models to estimate the number of (1) cardiovascular deaths averted due to blood pressure reductions; (2) potential hyperkalemia-related deaths from increased potassium intake in individuals with advanced chronic kidney disease; and (3) net averted deaths from nationwide salt substitution in India. We evaluated a conservative scenario, based on a large, long-term pragmatic trial in rural China; and an optimistic scenario informed by our recent trial in India. Sensitivity analyses were conducted to assess the robustness of the findings.Results: In the conservative scenario, a nationwide salt substitution intervention was estimated to result in approximate to 214 000 (95% uncertainty interval, 92 764-353 054) averted deaths from blood pressure reduction in the total population and approximate to 52 000 (22 961-80 211) in 28 million individuals with advanced chronic kidney disease, while approximate to 22 000 (15 221-31 840) hyperkalemia-deaths might be caused by the intervention. The corresponding estimates for the optimistic scenario were approximate to 351 000 (130 470-546 255), approximate to 66 000 (24 925-105 851), and approximate to 9000 (4251-14 599). Net benefits were consistent across sensitivity analyses.Conclusions: Modeling nationwide salt substitution in India consistently estimated substantial net benefits, preventing around 8% to 14% of annual cardiovascular deaths. Even allowing for potential hyperkalemia risks there were net benefits estimated for individuals with chronic kidney disease.
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