Publications by authors named "Olle Melander"

569 Publications

Causal Effect of Adiposity Measures on Blood Pressure Traits in 2 Urban Swedish Cohorts: A Mendelian Randomization Study.

J Am Heart Assoc 2021 Jun 14:e020405. Epub 2021 Jun 14.

Department of Medicine University of Verona Verona Italy.

Background Different adiposity traits may be causally related to hypertension in different ways. By using genetic variants as randomly allocated proxies for studying the effect of modifying adiposity traits, the Mendelian randomization approach can be used to investigate this. Methods and Results In this study, we used 4 different genetic risk scores (GRS; GRS-BMI, GRS-WHR, GRS-VAT, GRS-BF) including hundreds of single nucleotide polymorphisms associated with body mass index, waist-to-hip ratio, visceral adipose tissue, and body fat, respectively. These were applied as instrumental variables in Mendelian randomization analyses. Two Swedish urban-based cohort studies, the Malmö Diet and Cancer, and the Malmö Preventive 795Projects were used to obtain genetic association estimates with blood pressure (BP). In both the Malmö Preventive Projects and Malmö Diet and Cancer studies, except for that for body fat, all of the genetic risk scores were significantly associated with systolic BP and diastolic BP, but with different magnitudes. In particular, in both cohorts, each standard deviation increase in the genetic risk score made up by the 324 single nucleotide polymorphisms associated with waist-to-hip ratio was associated with doubling of the likelihood of hypertension prevalence at baseline. However, only the genetic risk score made up by the 565 SNPs associated with body mass index was significantly associated with hypertension incidence during 23.6±4.3 years of follow-up in the Malmö Preventive Project. Conclusions We support a causal link between genetically mediated adiposity, especially waist-to-hip ratio and body mass index, and BP traits including hypertension prevalence and, for the first time to our knowledge, hypertension incidence. The differences in magnitude between these associations might suggest different mechanisms by which different adiposity affects BP/hypertension and consequently may indicate that tailored interventions are needed to reduce cardiovascular risk.
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http://dx.doi.org/10.1161/JAHA.120.020405DOI Listing
June 2021

The association between length of stay in the emergency department and short-term mortality.

Intern Emerg Med 2021 Jun 10. Epub 2021 Jun 10.

Department of Clinical Sciences, Faculty of Medicine, Lund University, Malmö, Sweden.

The detrimental effects of increased length of stay at the emergency department (ED-LOS) for patient outcome have been sparsely studied in the Swedish setting. Our aim was to further explore the association between ED-LOS and short-term mortality in patients admitted to the EDs of two large University hospitals in Sweden. All adult patients (> 18 years) visiting the ED at the Karolinska University Hospital, Sweden, from 1/1/2010 to 1/1/2015 (n = 639,385) were retrospectively included. Logistic regression analysis was used to determine association between ED-LOS and 7- and 30-day mortality rates. All patients were triaged according to the RETTS-A into different levels of medical urgency and subsequently separated into five quintiles of ED-LOS. Mortality rate was highest in highest triage priority level (7-day mortality 5.24%, and 30-day mortality 9.44%), and decreased by lower triage priority group. For patients with triage priority levels 2-4, prolonged ED-LOS was associated with increased mortality, especially for lowest priority level, OR for priority level 4 and highest quintile of ED-LOS 30-day mortality 1.49 (CI 95% 1.20-1.85). For patients with highest triage priority level the opposite was at hand, with decreasing mortality risk with increasing quintile of ED-LOS for 7-day mortality, and lower mortality for the two highest quintile of ED-LOS for 30-day mortality. In patients not admitted to in-hospital care higher ED-LOS was associated with higher mortality. Our data suggest that increased ED-LOS could be associated with slightly increased short-term mortality in patients with lower clinical urgency and dismissed from the ED.
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http://dx.doi.org/10.1007/s11739-021-02783-zDOI Listing
June 2021

Dietary Data in the Malmö Offspring Study-Reproducibility, Method Comparison and Validation against Objective Biomarkers.

Nutrients 2021 May 9;13(5). Epub 2021 May 9.

Department of Clinical Sciences Malmö, Diabetes and Cardiovascular Disease-Genetic Epidemiology, Lund University, 205 02 Malmö, Sweden.

Irregular dietary intakes impairs estimations from food records. Biomarkers and method combinations can be used to improve estimates. Our aim was to examine reproducibility from two assessment methods, compare them, and validate intakes against objective biomarkers. We used the Malmö Offspring Study (55% women, 18-71 y) with data from a 4-day food record (4DFR) and a short food frequency questionnaire (SFFQ) to compare (1) repeated intakes ( = 180), (2) intakes from 4DFR and SFFQ ( = 1601), and (3) intakes of fatty fish, fruits and vegetables, and citrus with plasma biomarkers ( = 1433) (3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid [CMPF], β-carotene and proline betaine). We also combined 4DFR and SFFQ estimates using principal component analysis (PCA). Moderate correlations were seen between repeated intakes (4DFR median ρ = 0.41, SFFQ median ρ = 0.59) although lower for specific 4DFR-items, especially fatty/lean fish (ρ ≤ 0.08). Between-method correlations (median ρ = 0.33) were higher for intakes of overall food groups compared to specific foods. PCA scores for citrus (proline betaine ρ = 0.53) and fruits and vegetables (β-carotene: ρ = 0.39) showed the highest biomarker correlations, whereas fatty fish intake from the SFFQ per se showed the highest correlation with CMPF (ρ = 0.46). To conclude, the reproducibility of SFFQ data was superior to 4DFR data regarding irregularly consumed foods. Method combination could slightly improve fruit and vegetable estimates, whereas SFFQ data gave most valid fatty fish intake.
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http://dx.doi.org/10.3390/nu13051579DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8150333PMC
May 2021

Copeptin as a predictive marker of incident heart failure.

ESC Heart Fail 2021 May 30. Epub 2021 May 30.

Perinatal and Cardiovascular Epidemiology, Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.

Aims: Heart failure (HF) is a common disease with increasing prevalence and poor prognosis. The vasopressin (VP) marker copeptin predicts development of diabetes mellitus, diabetic heart disease, coronary artery disease, and premature mortality. Copeptin is elevated in HF patients and predicts a worse outcome. This study aims to investigate whether copeptin can predict HF development.

Methods: Copeptin was analysed in 5297 individuals (69.6% men) without prevalent HF from the Malmö Preventive Project, a population-based prospective cohort. Cox proportional hazards models were used to analyse risk of incident HF by copeptin levels after adjusting for conventional cardiovascular risk factors.

Results: During a median follow-up time of 11.1 years, 350 subjects (6.6%) were diagnosed with HF. Of these events, 99 were classified as myocardial infarction (MI) related HF and 251 as non-MI-related HF. Individuals in the top quartile of copeptin had, after multivariate adjustment for conventional risk factors (age, sex, systolic blood pressure, diabetes mellitus, body mass index, antihypertensive therapy, smoking, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol), a significantly increased risk of developing HF by 1.63 [confidence interval (CI) 1.20-2.21] for HF compared with the reference quartile 1. After adjustment for conventional risk factors, the hazard ratio (HR) per standard deviation increase of log-transformed copeptin for any HF was 1.30 (95% CI 1.17-1.46), whereas it was 1.39 (CI 1.13-1.71) for MI-related HF and 1.26 (CI 1.11-1.44) for non-MI-related HF. The associations remained after additional adjustment for estimated glomerular filtration rate [HR 1.24 (95% CI: 1.10-1.40)] and for pro atrial natriuretic peptide on top of conventional risk factors [HR 1.14 (95% CI: 1.02-1.28)].

Conclusions: Elevated copeptin predicts development of HF in older adults. Copeptin is a risk marker of VP-driven HF susceptibility and a candidate to guide prevention efforts of HF targeting the VP system.
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http://dx.doi.org/10.1002/ehf2.13439DOI Listing
May 2021

Low risk patients with acute atrial fibrillation and elevated high-sensitivity troponin do not have increased incidence of pathological stress tests.

Scand Cardiovasc J 2021 May 14:1-5. Epub 2021 May 14.

Department of Clinical Sciences, Lund University, Lund, Sweden.

Objectives: Many patients with atrial fibrillation (AF) or atrial flutter (AFL) and rapid ventricular response (RVR) have elevated high-sensitivity troponin T (hsTnT) values. Elevated hsTnT is an independent risk marker for cardiovascular events and mortality. The aim was to examine if AF/AFL patients with RVR and elevated hsTnT have an increased incidence of pathological cardiac stress tests, indicating need of further evaluation for coronary artery disease (CAD). We prospectively included 90 AF/AFL patients without known heart failure and CAD presenting with AF/AFL and RVR. Half of the patients had elevated hsTnT (cases) and half had levels below the 99th percentile (controls). All patients were discharged in sinus rhythm. After approximately one week in sinus rhythm a new hsTnT was analysed and the patients performed a bicycle exercise stress test within the 30 day follow-up. The primary endpoint was a pathological stress test confirmed by a pathological SPECT myocardial perfusion imaging or a coronary angiography. None of the controls reached the primary endpoint. Two patients (4%) out of the 45 cases reached the primary endpoint ( = .49 vs controls), but only one was found to have significant CAD at subsequent coronary angiography. Patients with paroxysmal AF/AFL, without a history of CAD and heart failure, who present with a RVR and minor hsTnT elevations were not found to have an increased incidence of pathological stress tests compared to patients with hsTnT values below the 99th percentile.
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http://dx.doi.org/10.1080/14017431.2021.1927171DOI Listing
May 2021

Clustering of blood cell count abnormalities and future risk of death.

Eur J Clin Invest 2021 May 7:e13562. Epub 2021 May 7.

Department of Clinical Sciences, Lund University, Malmö, Sweden.

Background: The identification of novel predictors of poor outcome may help stratify cardiovascular risk. Aim was to evaluate the individual contribution of blood cell count parameters, as well as their clustering, on the risk of death and cardiovascular events over the long term in the population-based Malmö Diet and Cancer Study cohort.

Methods: In 30,447 individuals (age 57 ± 8 years), we assessed the incidence of all-cause death (primary endpoint) and major adverse cardiovascular events (MACE, secondary outcome measure) according to absence or presence of one, two and three factors at baseline out of the following: anaemia, leukocytosis and thrombocytosis. Median follow-up was 16 years.

Results: The percentages of all-cause death were 19.5% in individuals without factors, 21.3% in those with one factor, 27.4% with two and 46.4% with three (log-rank test P < .001). The crude incidence of MACE was 28.0%, 29.2%, 35.5% and 57.1%, respectively (log-rank test P < .001). At multivariate analysis, we found a stepwise increase in overall mortality with increasing number of prevalent factors (one factor: HR 1.23, 95% CI 1.14-1.31, P < .001; two factors: 1.61, 1.37-1.89, P < .001; three factors: 2.69, 1.44-5.01, P = .002, vs no factor). Similar findings were observed for the incidence of MACE (one factor: adjusted HR 1.18, 95% CI 1.11-1.24, P < .001; two factors: 1.52, 1.33-1.76, P < .001; three factors: 2.03, 1.21-3.67, P < .001, vs no factor).

Conclusions: The easily assessable clustering of anaemia, leukocytosis and thrombocytosis heralds higher incidence of death and adverse cardiovascular events.
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http://dx.doi.org/10.1111/eci.13562DOI Listing
May 2021

Circulating levels of growth hormone in postural orthostatic tachycardia syndrome.

Sci Rep 2021 Apr 21;11(1):8575. Epub 2021 Apr 21.

Department of Clinical Sciences, Faculty of Medicine, Clinical Research Center, Lund University, Box 50332, 20213, Malmö, Sweden.

Postural orthostatic tachycardia syndrome (POTS) is a cardiovascular autonomic disorder with poorly understood etiology and underlying pathophysiology. Since cardiovascular morbidity has been linked to growth hormone (GH), we studied GH levels in patients with POTS. We conducted an age-sex-matched case-control study in patients with POTS (age 31 ± 9 years; n = 42) and healthy controls (32 ± 9 years; n = 46). Plasma GH levels were measured using high-sensitivity chemiluminescence sandwich immunoassay. The burden of orthostatic intolerance symptoms was assessed by the Orthostatic Hypotension Questionnaire (OHQ), consisting of a symptom assessment scale (OHSA) and a daily activity scale (OHDAS). POTS patients had significantly higher composite OHQ score than controls, more symptoms and less activity. Supine heart rate and diastolic blood pressure (BP), but not systolic BP, were significantly higher in POTS. Median plasma GH levels were significantly lower in POTS (0.53 ng/mL) than controls (2.33 ng/mL, p = 0.04). GH levels were inversely related to OHDAS in POTS and supine systolic BP in POTS and controls, but not heart rate neither group. POTS is associated with lower GH levels. Impairment of daily life activities is inversely related with GH in POTS. A higher supine diastolic BP is inversely associated with GH levels in POTS and healthy individuals.
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http://dx.doi.org/10.1038/s41598-021-87983-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8060383PMC
April 2021

The copy number variation and stroke (CaNVAS) risk and outcome study.

PLoS One 2021 19;16(4):e0248791. Epub 2021 Apr 19.

University of Maryland School of Medicine, Baltimore, MD, United States of America.

Background And Purpose: The role of copy number variation (CNV) variation in stroke susceptibility and outcome has yet to be explored. The Copy Number Variation and Stroke (CaNVAS) Risk and Outcome study addresses this knowledge gap.

Methods: Over 24,500 well-phenotyped IS cases, including IS subtypes, and over 43,500 controls have been identified, all with readily available genotyping on GWAS and exome arrays, with case measures of stroke outcome. To evaluate CNV-associated stroke risk and stroke outcome it is planned to: 1) perform Risk Discovery using several analytic approaches to identify CNVs that are associated with the risk of IS and its subtypes, across the age-, sex- and ethnicity-spectrums; 2) perform Risk Replication and Extension to determine whether the identified stroke-associated CNVs replicate in other ethnically diverse datasets and use biomarker data (e.g. methylation, proteomic, RNA, miRNA, etc.) to evaluate how the identified CNVs exert their effects on stroke risk, and lastly; 3) perform outcome-based Replication and Extension analyses of recent findings demonstrating an inverse relationship between CNV burden and stroke outcome at 3 months (mRS), and then determine the key CNV drivers responsible for these associations using existing biomarker data.

Results: The results of an initial CNV evaluation of 50 samples from each participating dataset are presented demonstrating that the existing GWAS and exome chip data are excellent for the planned CNV analyses. Further, some samples will require additional considerations for analysis, however such samples can readily be identified, as demonstrated by a sample demonstrating clonal mosaicism.

Conclusion: The CaNVAS study will cost-effectively leverage the numerous advantages of using existing case-control data sets, exploring the relationships between CNV and IS and its subtypes, and outcome at 3 months, in both men and women, in those of African and European-Caucasian descent, this, across the entire adult-age spectrum.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0248791PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055008PMC
April 2021

Replication study reveals miR-483-5p as an important target in prevention of cardiometabolic disease.

BMC Cardiovasc Disord 2021 Apr 1;21(1):162. Epub 2021 Apr 1.

Department of Clinical Sciences-Malmö, Hypertension and Cardiovascular Disease, Lund University, 205 02, Malmö, Sweden.

Background: Alterations in levels of circulating micro-RNAs might reflect within organ signaling or subclinical tissue injury that is linked to risk of diabetes and cardiovascular risk. We previously found that serum levels of miR-483-5p is correlated with cardiometabolic risk factors and incidence of cardiometabolic disease in a case-control sample from the populations-based Malmö Diet and Cancer Study Cardiovascular Cohort (MDC-CC). We here aimed at replicating these findings and to test for association with carotid atherosclerosis.

Methods: We measured miR-483-5p in fasting serum of 1223 healthy subjects from the baseline examination of the population-based, prospective cohort study Malmö Offspring Study (MOS) and correlated miR-483-5p to cardiometabolic risk factors and to incidence of diabetes mellitus and coronary artery disease (CAD) during 3.7 (± 1.3) years of follow-up using logistic regression. In both MOS and MDC-CC we related mir-483-5p to carotid atherosclerosis measured with ultrasound.

Results: In cross-sectional analysis miR-483-5p was correlated with BMI, waist circumference, HDL, and sex. After adjustment for age and sex, the association remained significant for all risk factors except for HDL. Logistic regression analysis showed significant associations between miR-483-5p and new-onset diabetes (OR = 1.94, 95% CI 1.06-3.56, p = 0.032) and cardiovascular disease (OR = 1.99, 95% CI 1.06-3.75, p = 0.033) during 3.7 (± 1.3) years of follow-up. Furthermore, miR-483-5p was significantly related with maximum intima-media thickness of the carotid bulb in MDC-CC (p = 0.001), but not in MOS, whereas it was associated with increasing number of plaques in MOS (p = 0.007).

Conclusion: miR-483-5p is related to an unfavorable cardiometabolic risk factor profile and predicts diabetes and CAD, possibly through an effect on atherosclerosis. Our results encourage further studies of possible underlying mechanisms and means of modifying miR-483-5p as a possible interventional target in prevention of cardiometabolic disease.
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http://dx.doi.org/10.1186/s12872-021-01964-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017779PMC
April 2021

Socioeconomic and Clinical Predictors of Mortality in Patients with Acute Dyspnea.

Open Access Emerg Med 2021 25;13:107-116. Epub 2021 Mar 25.

Department of Clinical Sciences, Lund University, Malmö, Sweden.

Background: Factors predicting long-term prognosis in patients with acute dyspnea may guide both acute management and follow-up. The aim of this study was to identify socioeconomic and clinical risk factors for all-cause mortality among acute dyspnea patients admitted to an Emergency Department.

Methods: We included 798 patients with acute dyspnea admitted to the ED of Skåne University Hospital, Malmö, Sweden from 2013 to 2016. Exposures were living in the immigrant-dense urban part of Malmö (IDUD), country of birth, annual income, comorbidities, smoking habits, medical triage priority and severity of dyspnea. Mean follow-up time was 2.2 years. Exposures were related to risk of all-cause mortality using Cox proportional hazard model.

Results: During follow-up 40% died. In models adjusted for age and gender, low annual income, previous or ongoing smoking, certain comorbidities, high medical triage priority and severe dyspnea were all significantly associated with increased mortality. After adjusting for age, gender and all significant exposures, the lowest quintile of income, ongoing or previous smoking, history of serious infection, anemia, hip fracture, high medical triage priority and severe dyspnea significantly and independently predicted mortality. In contrast, neither country of birth nor living in IDUD predicted a mortality risk.

Conclusion: Apart from several clinical risk factors, low annual income predicts two-year mortality risk in patients with acute dyspnea. This is not the case for country of birth and living in IDUD. Our results underline the wide range of mortality risk factors in acute dyspnea patients. Knowledge of patients' annual income as well as certain clinical features may aid risk stratification and determining the need of follow-up both in hospital and after discharge from an ED.
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http://dx.doi.org/10.2147/OAEM.S277448DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008092PMC
March 2021

The associations between red cell distribution width and plasma proteins in a general population.

Clin Proteomics 2021 Mar 30;18(1):12. Epub 2021 Mar 30.

Department of Clinical Sciences, Lund University, CRC Hus 60 plan 13, Jan Waldenströms gata 35, 20502, Malmö, Sweden.

Background: High red cell distribution width (RDW) has been increasingly recognized as a risk factor for cardiovascular diseases (CVDs), but the underlying mechanisms remain unknown. Our aim was to explore the associations between RDW and plasma proteins implicated in the pathogenesis of CVD using a targeted proteomics panel.

Methods: RDW and 88 plasma proteins were measured in a population-based cohort study (n = 4726), Malmö Diet and Cancer-Cardiovascular Cohort (MDC-CC). A random 2/3 of the cohort was used as discovery sample and remaining 1/3 was used for replication. Multiple linear regression was used to assess the associations between RDW and plasma proteins, with adjustments for age, sex, and other potential confounders. Proteins with Bonferroni-corrected significant associations with RDW in the discovery sub-cohort were validated in the replication cohort.

Results: Thirteen of 88 plasma proteins had significant associations with RDW in the discovery sample, after multivariate adjustments. Eleven of them were also significant in the replication sample, including SIR2-like protein 2 (SIRT2), stem cell factor (SCF, inversely), melusin (ITGB1BP2), growth differentiation factor-15 (GDF-15), matrix metalloproteinase-7 (MMP-7), hepatocyte growth factor (HGF), chitinase-3-like protein 1 (CHI3L1), interleukin-8 (IL-8), CD40 ligand (CD40-L), urokinase plasminogen activator surface receptor (U-PAR) and matrix metalloproteinase-3 (MMP-3).

Conclusions: Several proteins from this targeted proteomics panel were associated with RDW in this cohort. These proteins could potentially be linked to the increased cardiovascular risk in individuals with high RDW.
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http://dx.doi.org/10.1186/s12014-021-09319-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008679PMC
March 2021

A Journey through the Early Evidence Linking Hydration to Metabolic Health.

Ann Nutr Metab 2020 26;76 Suppl 1:4-9. Epub 2021 Mar 26.

Department of Clinical Science, Skåne University Hospital, Lund University, Malmö, Sweden.

The idea that water intake or hydration may play an intrinsic, independent role in modulating metabolic disease risk is relatively recent. Here, we outline the journey from early experimental works to more recent evidence linking water and hydration to metabolic health. It has been known for decades that individuals with existing metabolic dysfunction experience challenges to body water balance and have elevated arginine vasopressin (AVP), a key hormone regulating body fluid homeostasis. Later, intervention studies demonstrated that altering fluid balance in these individuals could worsen their condition, suggesting that hydration played a role in modulating glycemic control. More recently, observational and interventional studies in healthy individuals have implicated the hydration-vasopressin axis in the pathophysiology of metabolic diseases. Individuals with higher AVP (or its surrogate, copeptin) are at higher risk for developing type 2 diabetes and components of the metabolic syndrome, an association that remains even when controlling for known risk factors. Supporting preclinical work also suggests a causal role for AVP in metabolic dysfunction. It is known that individuals who habitually drink less fluids tend to have higher circulating AVP, which may be lowered by increasing water intake. In the short term, water supplementation in habitual low drinkers with high copeptin may reduce fasting glucose or glucagon, generating a proof of concept for the role of water supplementation in reducing incident metabolic disease. A large randomized trial is ongoing to determine whether water supplementation for 1 year in subjects with low water intake can meaningfully reduce fasting glucose, risk of new-onset diabetes, and other cardiometabolic risk factors.
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http://dx.doi.org/10.1159/000515021DOI Listing
March 2021

Methodological considerations for identifying multiple plasma proteins associated with all-cause mortality in a population-based prospective cohort.

Sci Rep 2021 Mar 24;11(1):6734. Epub 2021 Mar 24.

Diabetes and Cardiovascular Disease-Genetic Epidemiology, Department of Clinical Sciences in Malmö, Lund University, Clinical Research Centre House 60 Floor 13, Jan Waldenströms gata 35, 205 02, Malmö, Sweden.

Novel methods to characterize the plasma proteome has made it possible to examine a wide range of proteins in large longitudinal cohort studies, but the complexity of the human proteome makes it difficult to identify robust protein-disease associations. Nevertheless, identification of individuals at high risk of early mortality is a central issue in clinical decision making and novel biomarkers may be useful to improve risk stratification. With adjustment for established risk factors, we examined the associations between 138 plasma proteins measured using two proximity extension assays and long-term risk of all-cause mortality in 3,918 participants of the population-based Malmö Diet and Cancer Study. To examine the reproducibility of protein-mortality associations we used a two-step random-split approach to simulate a discovery and replication cohort and conducted analyses using four different methods: Cox regression, stepwise Cox regression, Lasso-Cox regression, and random survival forest (RSF). In the total study population, we identified eight proteins that associated with all-cause mortality after adjustment for established risk factors and with Bonferroni correction for multiple testing. In the two-step analyses, the number of proteins selected for model inclusion in both random samples ranged from 6 to 21 depending on the method used. However, only three proteins were consistently included in both samples across all four methods (growth/differentiation factor-15 (GDF-15), N-terminal pro-B-type natriuretic peptide, and epididymal secretory protein E4). Using the total study population, the C-statistic for a model including established risk factors was 0.7222 and increased to 0.7284 with inclusion of the most predictive protein (GDF-15; P < 0.0001). All multiple protein models showed additional improvement in the C-statistic compared to the single protein model (all P < 0.0001). We identified several plasma proteins associated with increased risk of all-cause mortality independently of established risk factors. Further investigation into the putatively causal role of these proteins for longevity is needed. In addition, the examined methods for identifying multiple proteins showed tendencies for overfitting by including several putatively false positive findings. Thus, the reproducibility of findings using such approaches may be limited.
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http://dx.doi.org/10.1038/s41598-021-85991-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7990913PMC
March 2021

Genome-wide association meta-analysis identifies pleiotropic risk loci for aerodigestive squamous cell cancers.

PLoS Genet 2021 Mar 5;17(3):e1009254. Epub 2021 Mar 5.

University of Salzburg, Department of Biosciences and Cancer Cluster Salzburg, Salzburg, Austria.

Squamous cell carcinomas (SqCC) of the aerodigestive tract have similar etiological risk factors. Although genetic risk variants for individual cancers have been identified, an agnostic, genome-wide search for shared genetic susceptibility has not been performed. To identify novel and pleotropic SqCC risk variants, we performed a meta-analysis of GWAS data on lung SqCC (LuSqCC), oro/pharyngeal SqCC (OSqCC), laryngeal SqCC (LaSqCC) and esophageal SqCC (ESqCC) cancers, totaling 13,887 cases and 61,961 controls of European ancestry. We identified one novel genome-wide significant (Pmeta<5x10-8) aerodigestive SqCC susceptibility loci in the 2q33.1 region (rs56321285, TMEM273). Additionally, three previously unknown loci reached suggestive significance (Pmeta<5x10-7): 1q32.1 (rs12133735, near MDM4), 5q31.2 (rs13181561, TMEM173) and 19p13.11 (rs61494113, ABHD8). Multiple previously identified loci for aerodigestive SqCC also showed evidence of pleiotropy in at least another SqCC site, these include: 4q23 (ADH1B), 6p21.33 (STK19), 6p21.32 (HLA-DQB1), 9p21.33 (CDKN2B-AS1) and 13q13.1(BRCA2). Gene-based association and gene set enrichment identified a set of 48 SqCC-related genes rel to DNA damage and epigenetic regulation pathways. Our study highlights the importance of cross-cancer analyses to identify pleiotropic risk loci of histology-related cancers arising at distinct anatomical sites.
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http://dx.doi.org/10.1371/journal.pgen.1009254DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968735PMC
March 2021

Proteomic profiling reveals biomarkers and pathways in type 2 diabetes risk.

JCI Insight 2021 Mar 8;6(5). Epub 2021 Mar 8.

Cardiovascular Institute.

Recent advances in proteomic technologies have made high-throughput profiling of low-abundance proteins in large epidemiological cohorts increasingly feasible. We investigated whether aptamer-based proteomic profiling could identify biomarkers associated with future development of type 2 diabetes (T2DM) beyond known risk factors. We identified dozens of markers with highly significant associations with future T2DM across 2 large longitudinal cohorts (n = 2839) followed for up to 16 years. We leveraged proteomic, metabolomic, genetic, and clinical data from humans to nominate 1 specific candidate to test for potential causal relationships in model systems. Our studies identified functional effects of aminoacylase 1 (ACY1), a top protein association with future T2DM risk, on amino acid metabolism and insulin homeostasis in vitro and in vivo. Furthermore, a loss-of-function variant associated with circulating levels of the biomarker WAP, Kazal, immunoglobulin, Kunitz, and NTR domain-containing protein 2 (WFIKKN2) was, in turn, associated with fasting glucose, hemoglobin A1c, and HOMA-IR measurements in humans. In addition to identifying potentially novel disease markers and pathways in T2DM, we provide publicly available data to be leveraged for insights about gene function and disease pathogenesis in the context of human metabolism.
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http://dx.doi.org/10.1172/jci.insight.144392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021115PMC
March 2021

Circulating pro-neurotensin levels predict bodyweight gain and metabolic alterations in children.

Nutr Metab Cardiovasc Dis 2021 03 5;31(3):902-910. Epub 2020 Dec 5.

Department of Clinical Medicine, Public Health, Life and Environmental Sciences (MeSVA), University of L'Aquila, Italy; Neuroendocrinology and Metabolic Diseases, IRCCS Neuromed, Pozzilli, Is, Italy. Electronic address:

Background And Aims: Neurotensin (NT) is an intestinal peptide released after fat ingestion, which regulates appetite and facilitates lipid absorption. Elevated plasma levels of its stable precursor pro-neurotensin (pro-NT) are associated with type 2 diabetes, obesity and cardiovascular mortality in adult populations; no data on pro-NT and metabolic disease are available in children. Aim of the study was to evaluate plasma pro-NT in relation to the presence of obesity in children, and to test if high pro-NT associates with the development of metabolic impairment later in life.

Methods And Results: For this longitudinal retrospective study, we studied 151 overweight/obese children undergoing metabolic evaluations at University of Cagliari, Italy. Pro-NT was also assessed in 46 normal-weight, age-, sex-comparable normal-weight children, selected as a reference group. At the baseline, pro-NT was comparable between overweight/obese and normal-weight children and correlated positively with age (p < 0.001), triglycerides (p < 0.001) and inversely with HDL levels (p = 0.008). Plasma pro-NT associated with high triglycerides with OR = 5.9 (95%CI: 1.24-28.1; p = 0.026) after adjustment for multiple confounders. At the 6.5-year follow-up, high basal pro-NT associated with impaired β-cell function to compensate for insulin-resistance (disposition index: r = -0.19, p = 0.035) and predicted bodyweight increase, as indicated by percentage change of standard deviation score BMI (median(95%CI) = +20.8(+4.9-+27.5)% in the highest tertile), independently from age, sex, triglycerides and insulin-resistance (standardized β = 0.24; p = 0.036).

Conclusions: Elevated pro-NT levels in children are significantly associated with weight gain later in life and may represent a marker of susceptibility to metabolic impairment in presence of obesity.
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http://dx.doi.org/10.1016/j.numecd.2020.11.025DOI Listing
March 2021

A plasma lipid signature predicts incident coronary artery disease.

Int J Cardiol 2021 05 3;331:249-254. Epub 2021 Feb 3.

Department of Clinical Sciences, Lund University, Malmö, Sweden.

Background: Dyslipidemia is a hallmark of cardiovascular disease but is characterized by crude measurements of triglycerides, HDL- and LDL cholesterol. Lipidomics enables more detailed measurements of plasma lipids, which may help improve risk stratification and understand the pathophysiology of cardiovascular disease.

Methods: Lipidomics was used to measure 184 lipids in plasma samples from the Malmö Diet and Cancer - Cardiovascular Cohort (N = 3865), taken at baseline examination. During an average follow-up time of 20.3 years, 536 participants developed coronary artery disease (CAD). Least absolute shrinkage and selection operator (LASSO) were applied to Cox proportional hazards models in order to identify plasma lipids that predict CAD.

Results: Eight plasma lipids improved prediction of future CAD on top of traditional cardiovascular risk factors. Principal component analysis of CAD-associated lipids revealed one principal component (PC2) that was associated with risk of future CAD (HR per SD increment =1.46, C·I = 1.35-1.48, P < 0.001). The risk increase for being in the highest quartile of PC2 (HR = 2.33, P < 0.001) was higher than being in the top quartile of systolic blood pressure. Addition of PC2 to traditional risk factors achieved an improvement (2%) in the area under the ROC-curve for CAD events occurring within 10 (P = 0.03), 15 (P = 0.003) and 20 (P = 0.001) years of follow-up respectively.

Conclusions: A lipid pattern improve CAD prediction above traditional risk factors, highlighting that conventional lipid-measures insufficiently describe dyslipidemia that is present years before CAD. Identifying this hidden dyslipidemia may help motivate lifestyle and pharmacological interventions early enough to reach a substantial reduction in absolute risk.
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http://dx.doi.org/10.1016/j.ijcard.2021.01.059DOI Listing
May 2021

Circulating Vimentin Is Associated With Future Incidence of Stroke in a Population-Based Cohort Study.

Stroke 2021 Mar 4;52(3):937-944. Epub 2021 Feb 4.

Department of Clinical Sciences in Malmö, Lund University, Malmö, Sweden (J.X., O.M., M.O.-M., J.N., Y.B., G.E.).

Background And Purpose: VIM (vimentin) is a cytoskeletal intermediate filament protein, which has been linked to atherosclerosis and thrombosis; both are important causes of stroke. We examined the relationship between circulating VIM and incidence of stroke, and if carotid plaque could modify the association in a prospective population-based cohort.

Methods: This prospective study was based on the Malmö Diet and Cancer Cohort. A total of 4688 participants (39.7% men; mean age, 57.6 years) were examined and blood samples were collected between 1991 and 1994. Incidence of stroke was followed up to 2018. Cox' proportional hazards regression was used to assess the relationship between VIM and stroke.

Results: During a mean follow-up of 22.0 years, a total of 528 subjects were diagnosed with stroke, among which 434 were ischemic stroke. Participants in the highest quartile (vs 1 quartile) had 1.34× higher risk of total stroke (95% CI, 1.03-1.74) and 1.47× higher of ischemic stroke (95% CI, 1.10-1.98) after adjustment for potential confounders. A significant interaction was found between carotid plaque and VIM with respect to incidence of both total stroke and ischemic stroke (=0.041 and 0.011, respectively). After stratifying by carotid plaque, high VIM had stronger association with stroke in participants with carotid plaque, especially for the risk of ischemic stroke (adjusted hazard ratio,1.66 [95% CI, 1.23-2.25] for quartile 4 versus quartile 1 to 3).

Conclusions: VIM is positively associated with the incidence of stroke, especially in individuals with carotid plaque. Further studies are needed to confirm the observed associations.
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http://dx.doi.org/10.1161/STROKEAHA.120.032111DOI Listing
March 2021

Comparison of cardiovascular disease and cancer prevalence between Mediterranean and north European middle-aged populations (The Cilento on Ageing Outcomes Study and The Malmö Offspring Study).

Intern Emerg Med 2021 Jan 30. Epub 2021 Jan 30.

Department of Medical-Surgery Sciences and Translational Medicine, University of Rome Sapienza, Rome, Italy.

Mediterranean diet protects from both cardiovascular disease (CVD) and cancer. In the 1960s, Ancel Keys defined the concept of Mediterranean diet in the South Italian region of Cilento and proposed it as a key factor for healthy ageing in the region. The aim of the current study was to compare the prevalence of CVD and cancer between a middle-aged population from Cilento and those of a Northern European population from Malmö, Sweden. We clinically characterized two middle-aged (50-67 years of age) population-based samples from Cilento (n = 809) and Malmö (n = 1025), Sweden, respectively. Logistic regression was used to calculate odds ratios (95% confidence interval) for disease prevalence in Malmö versus Cilento inhabitants adjusted for age and sex (model 1) and adjusted for all cardiometabolic risk factors (model 2). The prevalence of hypertension, current smoking, diabetes mellitus and levels of body mass index and triglycerides were lower, whereas HDL-cholesterol was higher in Malmö than in Cilento. LDL-cholesterol was higher and estimated glomerular filtration rate was lower in Malmö than in Cilento. The odds ratio for cardiovascular disease in Malmö versus Cilento inhabitants was 1.13 (0.69-1.87) (P = 0.62) in model 1, whereas it was significantly elevated in model 2 [2.03 (1.14-3.60) (P = 0.016)]. Moreover, the odds ratio for cancer in Malmö versus Cilento was 2.78 (1.81-4.27) (P < 0.001) in model 1 and 3.11 (1.97-4.92) (P < 0.001) in model 2. The higher odds of CVD and cancer in Malmö versus Cilento, when risk factors were accounted for, suggests the existence of unknown protective factors in Cilento.
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http://dx.doi.org/10.1007/s11739-020-02625-4DOI Listing
January 2021

Vasoactive Biomarkers Associated With Long-Term Incidence of Symptomatic Peripheral Arterial Disease and Mortality.

Angiology 2021 Jul 28;72(6):550-555. Epub 2021 Jan 28.

Department of Clinical Sciences, Malmö, 5193Lund University, Sweden.

We evaluated if plasma biomarkers can predict incident peripheral arterial disease (PAD) and mortality in a longitudinal cohort study. Men (n = 3618) and women (n = 1542) were included in the Malmö Preventive Project and underwent analysis of: C-terminal endothelin-1 (CT-proET-1), N-Terminal prosomatostatin (NT-proSST), midregional proatrial natriuretic peptide (MR-proANP), procalcitonin (PCT), and copeptin. Participants were followed up for incident PAD and mortality until December 31, 2016. Median follow-up was 11.2 years (interquartile range 9.4-12.2). Cumulative incidence of PAD was 4.3% (221/5160), 4.5% in men (164/3618) and 3.7% in women (57/1542; = .174). In an adjusted Cox proportional hazards regression model, higher CT-proET-1 (hazard ratio [HR] 1.8; 95% confidence interval [CI] 1.4-2.3), NT-proSST (HR 1.5; 95% CI 1.2-2.0), and MR-proANP (HR 1.7; 95% CI 1.3-2.3) were independently associated with incident PAD, and higher CT-proET-1 (HR 1.3; 95% CI 1.2-1.5), NT-proSST (HR 1.2; 95% CI 1.1-1.3), MR-proANP (HR 1.4; 95% CI 1.3-1.6), PCT (HR 1.1; 95% CI 1.0-1.2), and copeptin (HR 1.2; 95% CI 1.1-1.4) were independently associated with mortality. Increased levels of CT-proET-1, NT-proSST, and MR-proANP were independently associated with incident PAD, whereas all the vasoactive biomarkers were independently associated with mortality during follow-up.
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http://dx.doi.org/10.1177/0003319720987739DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8135239PMC
July 2021

Growth differentiation factor-15 is a biomarker for all-cause mortality but less evident for cardiovascular outcomes: A prospective study.

Am Heart J 2021 04 6;234:81-89. Epub 2021 Jan 6.

Department of Clinical Sciences, Malmö, Lund University, Malmö, Sweden. Electronic address:

Background: Previous studies have proposed growth differentiation factor-15 (GDF-15) as a predictor of adverse cardiovascular outcomes and mortality. The present study aimed to determine if such associations remain after accounting for death as a competing risk, and if GDF-15 provides superior prediction performance than other biomarkers.

Methods: Plasma GDF-15 levels and cardiovascular risk factors were measured in individuals without cardiovascular diseases (n = 4,143, aged 57.4 ± 5.96 years, 38.6 % men) from Malmö Diet and Cancer-Cardiovascular Cohort and were followed up for more than 20 years. Incidence of coronary events, ischemic stroke, cardiovascular mortality, and all-cause mortality was studied in relation to GDF-15 using Cox proportional hazards regression, with adjustment for potential confounders. Confounding from death as competing risk was carefully checked using the Fine and Gray subdistribution hazard model. Predictive capabilities were further evaluated using C-statistics, continuous net reclassification improvement, and integrated discrimination improvement.

Results: During follow-up, 424 coronary events, 327 ischemic stroke, 368 cardiovascular deaths, and 1,308 all-cause deaths occurred. After controlling for death from other causes as competing events, only all-cause mortality remained significantly related to GDF-15. The addition of GDF-15 significantly improved prediction for all-cause mortality in addition to the traditional risk factors, high-sensitive C-reactive protein and N-terminal prohormone of brain natriuretic peptide. Only N-terminal prohormone of brain natriuretic peptide improved prediction for CVD mortality.

Conclusions: GDF-15 is a robust biomarker for all-cause mortality but less reliable for coronary event, ischemic stroke or cardiovascular mortality. Competing risk from death is an important consideration when interpreting the results.
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http://dx.doi.org/10.1016/j.ahj.2020.12.020DOI Listing
April 2021

Evidence for a protective role of placental growth factor in cardiovascular disease.

Sci Transl Med 2020 12;12(572)

Department of Clinical Sciences Malmö, Lund University, 21428 Malmö, Sweden.

Placental growth factor (PlGF) is a mitogen for endothelial cells, but it can also act as a proinflammatory cytokine. Because it promotes early stages of plaque formation in experimental models of atherosclerosis and was implicated in epidemiological associations with risk of cardiovascular disease (CVD), PlGF has been attributed a pro-atherogenic role. Here, we investigated whether PlGF has a protective role in CVD and whether elevated PlGF reflects activation of repair processes in response to vascular stress. In a population cohort of 4742 individuals with 20 years of follow-up, high baseline plasma PlGF was associated with increased risk of cardiovascular death, myocardial infarction, and stroke, but these associations were lost or weakened when adjusting for cardiovascular risk factors known to cause vascular stress. Exposure of cultured endothelial cells to high glucose, oxidized low-density lipoprotein (LDL) or an inducer of apoptosis enhanced the release of PlGF. Smooth muscle cells and endothelial cells treated with PlGF small interference RNA demonstrated that autocrine PlGF stimulation plays an important role in vascular repair responses. High expression of PlGF in human carotid plaques removed at surgery was associated with a more stable plaque phenotype and a lower risk of future cardiovascular events. When adjusting associations of PlGF with cardiovascular risk in the population cohort for plasma soluble tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor-2, a biomarker of cellular stress, a high PlGF/TRAIL receptor-2 ratio was associated with a lower risk. Our findings provide evidence for a protective role of PlGF in CVD.
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http://dx.doi.org/10.1126/scitranslmed.abc8587DOI Listing
December 2020

Plant foods, dietary fibre and risk of ischaemic heart disease in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

Int J Epidemiol 2021 03;50(1):212-222

Department of Public Health and Clinical Medicine, Section of Sustainable Health/Nutritional Research, Umeå University, Umeå, Sweden.

Background: Epidemiological evidence indicates that diets rich in plant foods are associated with a lower risk of ischaemic heart disease (IHD), but there is sparse information on fruit and vegetable subtypes and sources of dietary fibre. This study examined the associations of major plant foods, their subtypes and dietary fibre with risk of IHD in the European Prospective Investigation into Cancer and Nutrition (EPIC).

Methods: We conducted a prospective analysis of 490 311 men and women without a history of myocardial infarction or stroke at recruitment (12.6 years of follow-up, n cases = 8504), in 10 European countries. Dietary intake was assessed using validated questionnaires, calibrated with 24-h recalls. Multivariable Cox regressions were used to estimate hazard ratios (HR) of IHD.

Results: There was a lower risk of IHD with a higher intake of fruit and vegetables combined [HR per 200 g/day higher intake 0.94, 95% confidence interval (CI): 0.90-0.99, P-trend = 0.009], and with total fruits (per 100 g/day 0.97, 0.95-1.00, P-trend = 0.021). There was no evidence for a reduced risk for fruit subtypes, except for bananas. Risk was lower with higher intakes of nuts and seeds (per 10 g/day 0.90, 0.82-0.98, P-trend = 0.020), total fibre (per 10 g/day 0.91, 0.85-0.98, P-trend = 0.015), fruit and vegetable fibre (per 4 g/day 0.95, 0.91-0.99, P-trend = 0.022) and fruit fibre (per 2 g/day 0.97, 0.95-1.00, P-trend = 0.045). No associations were observed between vegetables, vegetables subtypes, legumes, cereals and IHD risk.

Conclusions: In this large prospective study, we found some small inverse associations between plant foods and IHD risk, with fruit and vegetables combined being the most strongly inversely associated with risk. Whether these small associations are causal remains unclear.
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http://dx.doi.org/10.1093/ije/dyaa155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938513PMC
March 2021

Blood pressure and bladder cancer risk in men by use of survival analysis and in interaction with NAT2 genotype, and by Mendelian randomization analysis.

PLoS One 2020 25;15(11):e0241711. Epub 2020 Nov 25.

Department of Clinical Sciences in Lund, Lund University, Lund, Sweden.

The association between blood pressure (BP) and bladder cancer (BC) risk remains unclear with confounding by smoking being of particular concern. We investigated the association between BP and BC risk among men using conventional survival-analysis, and by Mendelian Randomization (MR) analysis in an attempt to disconnect the association from smoking. We additionally investigated the interaction between BP and N-acetyltransferase-2 (NAT2) rs1495741, an established BC genetic risk variant, in the association. Populations consisting of 188,167 men with 502 incident BC's in the UK-biobank and 27,107 men with 928 incident BC's in two Swedish cohorts were used for the analysis. We found a positive association between systolic BP and BC risk in Cox-regression survival analysis in the Swedish cohorts, (hazard ratio [HR] per standard deviation [SD]: 1.14 [95% confidence interval 1.05-1.22]) and MR analysis (odds ratio per SD: 2-stage least-square regression, 7.70 [1.92-30.9]; inverse-variance weighted estimate, 3.43 [1.12-10.5]), and no associations in the UK-biobank (HR systolic BP: 0.93 [0.85-1.02]; MR OR: 1.24 [0.35-4.40] and 1.37 [0.43-4.37], respectively). BP levels were positively associated with muscle-invasive BC (MIBC) (HRs: systolic BP, 1.32 [1.09-1.59]; diastolic BP, 1.27 [1.04-1.55]), but not with non-muscle invasive BC, which could be analyzed in the Swedish cohorts only. There was no interaction between BP and NAT2 in relation to BC on the additive or multiplicative scale. These results suggest that BP might be related to BC, more particularly MIBC. There was no evidence to support interaction between BP and NAT2 in relation to BC in our study.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0241711PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7688142PMC
December 2020

Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals.

Nat Genet 2020 12 23;52(12):1314-1332. Epub 2020 Nov 23.

Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark.

Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to ~1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency ≤ 0.01) variant BP associations (P < 5 × 10), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were ~8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets.
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http://dx.doi.org/10.1038/s41588-020-00713-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610439PMC
December 2020

Clinical Evaluation of the Polygenetic Background of Blood Pressure in the Population-Based Setting.

Hypertension 2021 01 23;77(1):169-177. Epub 2020 Nov 23.

Department of Emergency and Internal Medicine, Skåne University Hospital, Malmö, Sweden (O.M.).

The clinical value of the polygenetic component of blood pressure (BP) is commonly questioned. We evaluated a genetic risk score for BP (BP-GRS), based on the most recently published genome-wide association studies variants that were significantly associated with either systolic BP or diastolic BP, for prediction of hypertension and cardiovascular end points. The genotyping was performed in 2 urban-based prospective cohorts: the Malmö Diet and Cancer (n=29 295) and the Malmö Preventive Project (n=9367) and a weighted BP-GRS based on 858 SNPs was calculated. At baseline, we found a difference of 9.0 mm Hg (systolic BP) and 4.8 mm Hg (diastolic BP) between the top and the bottom quartile of BP-GRS. In Malmö Preventive Project, the top versus bottom quartile of BP-GRS was associated with a doubled risk of incident hypertension (odds ratio, 2.05 [95% CI, 1.75-2.39], =1.4×10), a risk higher than that of body mass index, as evaluated in quartiles. In Malmö Diet and Cancer, significant association was found between the age and sex-adjusted BP-GRS and the incidence of total cardiovascular events, stroke, coronary artery disease, heart failure, atrial fibrillation, and total mortality. Most of these associations remained significant after adjusting for traditional risk factors, including hypertension. BP-GRS could contribute predictive information regarding future hypertension, with an effect size comparable to other well-known risk factors such as obesity, and predicts cardiovascular events. Given that the exposure to high polygenetic risk starts at birth, we suggest that the BP-GRS might be useful to identify children or adolescents who would benefit from early hypertension screening and treatment.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.15449DOI Listing
January 2021