Publications by authors named "Anna F Dominiczak"

245 Publications

Mechanistic interactions of uromodulin with the thick ascending limb: perspectives in physiology and hypertension.

J Hypertens 2021 Aug;39(8):1490-1504

BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom.

Hypertension is a significant risk factor for cardiovascular disease and mortality worldwide. The kidney is a major regulator of blood pressure and electrolyte homeostasis, with monogenic disorders indicating a link between abnormal ion transport and salt-sensitive hypertension. However, the association between salt and hypertension remains controversial. Thus, there is continued interest in deciphering the molecular mechanisms behind these processes. Uromodulin (UMOD) is the most abundant protein in the normal urine and is primarily synthesized by the thick ascending limb epithelial cells of the kidney. Genome-wide association studies have linked common UMOD variants with kidney function, susceptibility to chronic kidney disease and hypertension independent of renal excretory function. This review will discuss and provide predictions on the role of the UMOD protein in renal ion transport and hypertension based on current observational, biochemical, genetic, pharmacological and clinical evidence.
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http://dx.doi.org/10.1097/HJH.0000000000002861DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7611110PMC
August 2021

CONNed in Pregnancy.

Hypertension 2021 Jul 1;78(1):241-249. Epub 2021 Jun 1.

Division of Experimental Medicine and Immuno-therapeutics, University of Cambridge, United Kingdom (I.B.W.).

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http://dx.doi.org/10.1161/HYPERTENSIONAHA.121.17021DOI Listing
July 2021

Echocardiography Predictors of Survival in Hypertensive Patients With Left Ventricular Hypertrophy.

Am J Hypertens 2021 06;34(6):636-644

Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.

Background: Left ventricular hypertrophy (LVH) is a well-known target organ damage. Concentric hypertrophy is the strongest predictor of increased risk of cardiovascular events, but the predictive value of individual echocardiographic parameters remains unclear.The aim of this study was to search for echocardiographic and hemodynamic variables associated with concentric and eccentric remodeling and their association with long-term cardiovascular outcomes.

Methods: Patients with echocardiography performed within 1 year prior to the initial clinic visit were included into the study. Logistic regression and multivariable Cox-proportional hazards were calculated according to several risk factors and variables. Additionally, cubic spline interpolation was used.

Results: We observed 690 patients for 10 years. There was a total of 177 major adverse cardiac and cerebrovascular events (MACCE) and 90 deaths over a 10-year period. Left ventricular concentric hypertrophy is associated with worse outcomes than eccentric hypertrophy in hypertensive subjects. Interestingly, different echocardiographic parameters contributed to risk depending on type of hypertrophy. In concentric hypertrophy, relative wall thickness provides linear prediction of risk for all-cause mortality (ACM) and composite endpoint. Systolic blood pressure is a significant predictor of MACCE. Blood pressure variability also showed significant predictive value for MACCE and ACM.

Conclusions: These data indicate risk stratification based on LVH need to consider different measures based on the type of remodeling.
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http://dx.doi.org/10.1093/ajh/hpaa194DOI Listing
June 2021

Artificial Intelligence in Hypertension: Seeing Through a Glass Darkly.

Circ Res 2021 Apr 1;128(7):1100-1118. Epub 2021 Apr 1.

BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow.

Hypertension remains the largest modifiable cause of mortality worldwide despite the availability of effective medications and sustained research efforts over the past 100 years. Hypertension requires transformative solutions that can help reduce the global burden of the disease. Artificial intelligence and machine learning, which have made a substantial impact on our everyday lives over the last decade may be the route to this transformation. However, artificial intelligence in health care is still in its nascent stages and realizing its potential requires numerous challenges to be overcome. In this review, we provide a clinician-centric perspective on artificial intelligence and machine learning as applied to medicine and hypertension. We focus on the main roadblocks impeding implementation of this technology in clinical care and describe efforts driving potential solutions. At the juncture, there is a critical requirement for clinical and scientific expertise to work in tandem with algorithmic innovation followed by rigorous validation and scrutiny to realize the promise of artificial intelligence-enabled health care for hypertension and other chronic diseases.
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http://dx.doi.org/10.1161/CIRCRESAHA.121.318106DOI Listing
April 2021

Renovascular Hypertension: One Size Does Not Fit All: Challenges in Diagnosis and Management.

Hypertension 2021 Apr 10;77(4):1022-1028. Epub 2021 Mar 10.

Division of Nephrology, Hypertension and Renal Transplantation, University of Florida, Gainesville (A.K., G.C., R.M.).

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http://dx.doi.org/10.1161/HYPERTENSIONAHA.121.17022DOI Listing
April 2021

Evaluating transition in Turner syndrome in the West of Scotland.

J Pediatr Endocrinol Metab 2021 Apr 26;34(4):473-477. Epub 2021 Feb 26.

Department of Paediatric Endocrinology, Royal Hospital for Children, Glasgow, UK.

Background: A Turner Syndrome (TS) Transition clinic, Royal Hospital for Children Glasgow (RHCG), with paediatric and adult endocrinology/gynaecology teams was established in 1998 with an aim of improving health outcomes in TS throughout the lifespan.

Objective: To evaluate the success of our TS transition service, focussing on evaluating established follow-up after transfer to adult services.

Methods: Girls attending the TS Transition clinic at Royal Hospital for Children Glasgow, 1998-2017, were identified. Attendance data were obtained from patient records and an electronic appointment system. We assessed good and late early attendance in our cohort of TS patients as well as established endocrine follow-up, defined as those still attending adult endocrine services 3 years after transfer. Success of TS transition was determined by the proportion of girls in established endocrine follow-up.

Results: Forty-six girls (median age 18.3 yrs) were identified. Thirty-six, 36/46 girls transferred prior to 2015 and 26 of those (72%) were in established follow-up at 3 years, 22/36 girls had met with an Adult specialist prior to transfer and 14/36 had not met with an adult specialist prior to transfer. Twenty-one (80.7%) were good early attenders (p = 0.10). In the early attenders' cohort, there was no significant difference between those that had and had not met an adult specialist prior to transfer.

Conclusion: A significant proportion of girls with TS are currently lost to endocrine follow-up following transfer to adult clinics. Early attendance at an adult clinic appears to predict established long-term follow-up. Strategies to improve early attendance and long-term endocrine follow-up are needed to ensure lifelong health needs are addressed.
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http://dx.doi.org/10.1515/jpem-2020-0242DOI Listing
April 2021

Hypertension: Update 2021.

Hypertension 2021 01 8;77(1):4-5. Epub 2020 Dec 8.

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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.16668DOI Listing
January 2021

Genetic predisposition to hypertension is associated with preeclampsia in European and Central Asian women.

Nat Commun 2020 11 25;11(1):5976. Epub 2020 Nov 25.

Medical and Clinical Genetics, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Preeclampsia is a serious complication of pregnancy, affecting both maternal and fetal health. In genome-wide association meta-analysis of European and Central Asian mothers, we identify sequence variants that associate with preeclampsia in the maternal genome at ZNF831/20q13 and FTO/16q12. These are previously established variants for blood pressure (BP) and the FTO variant has also been associated with body mass index (BMI). Further analysis of BP variants establishes that variants at MECOM/3q26, FGF5/4q21 and SH2B3/12q24 also associate with preeclampsia through the maternal genome. We further show that a polygenic risk score for hypertension associates with preeclampsia. However, comparison with gestational hypertension indicates that additional factors modify the risk of preeclampsia.
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http://dx.doi.org/10.1038/s41467-020-19733-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7688949PMC
November 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

Genomics of hypertension: the road to precision medicine.

Nat Rev Cardiol 2021 Apr 20;18(4):235-250. Epub 2020 Nov 20.

BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.

The known genetic architecture of blood pressure now comprises >30 genes, with rare variants resulting in monogenic forms of hypertension or hypotension and >1,477 common single-nucleotide polymorphisms (SNPs) being associated with the blood pressure phenotype. Monogenic blood pressure syndromes predominantly involve the renin-angiotensin-aldosterone system and the adrenal glucocorticoid pathway, with a smaller fraction caused by neuroendocrine tumours of the sympathetic and parasympathetic nervous systems. The SNPs identified in genome-wide association studies (GWAS) as being associated with the blood pressure phenotype explain only approximately 27% of the 30-50% estimated heritability of blood pressure, and the effect of each SNP on the blood pressure phenotype is small. A paucity of SNPs from GWAS are mapped to known genes causing monogenic blood pressure syndromes. For example, a GWAS signal mapped to the gene encoding uromodulin has been shown to affect blood pressure by influencing sodium homeostasis, and the effects of another GWAS signal were mediated by endothelin. However, the majority of blood pressure-associated SNPs show pleiotropic associations. Unravelling these associations can potentially help us to understand the underlying biological pathways. In this Review, we appraise the current knowledge of blood pressure genomics, explore the causal pathways for hypertension identified in Mendelian randomization studies and highlight the opportunities for drug repurposing and pharmacogenomics for the treatment of hypertension.
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http://dx.doi.org/10.1038/s41569-020-00466-4DOI Listing
April 2021

Uncontrolled Hypertension in an Elderly Man on Multiple Antihypertensive Drugs.

Hypertension 2020 12 26;76(6):1658-1663. Epub 2020 Oct 26.

From the Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN (M.R.D., S.J.T., G.L.S.), Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom.

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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.15310DOI Listing
December 2020

Woman With Polycystic Kidney Disease: The Role of Precision Medicine in Hypertension Management.

Hypertension 2020 11 21;76(5):1332-1338. Epub 2020 Sep 21.

From the Department of Medicine (D.C., D.W.J.), University of Mississippi Medical Center, Jackson.

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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.15021DOI Listing
November 2020

Case of Episodic and Positional Hypertension: Diagnosis and Treatment.

Hypertension 2020 09 20;76(3):614-621. Epub 2020 Jul 20.

From the Vascular Biology and Hypertension Program, Division of Cardiovascular Disease, Department of Medicine (M.S., D.A.C., S.O., T.D.), University of Alabama at Birmingham.

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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.15243DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7429316PMC
September 2020

Resistant Hypertension in a Dialysis Patient.

Hypertension 2020 08 29;76(2):278-287. Epub 2020 Jun 29.

From the Department of Renal Medicine, Royal Infirmary of Edinburgh (P.J.G., T.E.F., N.D.).

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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.15022DOI Listing
August 2020

Hypertension: Update 2020.

Hypertension 2020 01 2;75(1):3-4. Epub 2019 Dec 2.

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http://dx.doi.org/10.1161/HYPERTENSIONAHA.119.14352DOI Listing
January 2020

KCND3 potassium channel gene variant confers susceptibility to electrocardiographic early repolarization pattern.

JCI Insight 2019 12 5;4(23). Epub 2019 Dec 5.

Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.

BACKGROUNDThe presence of an early repolarization pattern (ERP) on the surface ECG is associated with risk of ventricular fibrillation and sudden cardiac death. Family studies have shown that ERP is a highly heritable trait, but molecular genetic determinants are unknown.METHODSTo identify genetic susceptibility loci for ERP, we performed a GWAS and meta-analysis in 2,181 cases and 23,641 controls of European ancestry.RESULTSWe identified a genome-wide significant (P < 5 × 10-8) locus in the potassium voltage-gated channel subfamily D member 3 (KCND3) gene that was successfully replicated in additional 1,124 cases and 12,510 controls. A subsequent joint meta-analysis of the discovery and replication cohorts identified rs1545300 as the lead SNP at the KCND3 locus (OR 0.82 per minor T allele, P = 7.7 × 10-12) but did not reveal additional loci. Colocalization analyses indicate causal effects of KCND3 gene expression levels on ERP in both cardiac left ventricle and tibial artery.CONCLUSIONSIn this study, we identified for the first time to our knowledge a genome-wide significant association of a genetic variant with ERP. Our findings of a locus in the KCND3 gene provide insights not only into the genetic determinants but also into the pathophysiological mechanism of ERP, discovering a promising candidate for functional studies.FUNDINGThis project was funded by the German Center for Cardiovascular Research (DZHK Shared Expertise SE081 - STATS). For detailed funding information per study, see the Supplemental Acknowledgments.
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http://dx.doi.org/10.1172/jci.insight.131156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6962032PMC
December 2019

Progressive Hypertension and Severe Left Ventricular Outflow Tract Obstruction.

Hypertension 2019 12 7;74(6):1216-1225. Epub 2019 Oct 7.

From the Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, United Kingdom (A.C.C., N.N.L., A.F.D., R.M.T., C.D.).

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http://dx.doi.org/10.1161/HYPERTENSIONAHA.119.13343DOI Listing
December 2019

Paroxysmal Hypertension Associated With Urination.

Hypertension 2019 11 30;74(5):1068-1074. Epub 2019 Sep 30.

From the Department of Hypertension, Fuwai Hospital, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China (Y.L., L.F., J.C., H.Z.).

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http://dx.doi.org/10.1161/HYPERTENSIONAHA.119.13140DOI Listing
November 2019

Paroxysmal Hypertension Associated With Presyncope.

Hypertension 2019 10 3;74(4):718-725. Epub 2019 Sep 3.

From the Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (J.M.L., C.P.C., J.A.O.).

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http://dx.doi.org/10.1161/HYPERTENSIONAHA.119.13341DOI Listing
October 2019

Diastolic Blood Pressure J-Curve Phenomenon in a Tertiary-Care Hypertension Clinic.

Hypertension 2019 10 19;74(4):767-775. Epub 2019 Aug 19.

From the Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom (S.L., L.E.T., P.J., L.M., A.F.D., S.P.).

Concerns exist regarding the potential increased cardiovascular risk from lowering diastolic blood pressure (DBP) in hypertensive patients. We analyzed 30-year follow-up data of 10 355 hypertensive patients attending the Glasgow Blood Pressure Clinic. The association between blood pressure during the first 5 years of treatment and cause-specific hospital admissions or mortality was analyzed using multivariable adjusted Cox proportional hazard models. The primary outcome was a composite of cardiovascular admissions and deaths. DBP showed a U-shaped association (nadir, 92 mm Hg) for the primary cardiovascular outcome hazard and a reverse J-shaped association with all-cause mortality (nadir, 86 mm Hg) and noncardiovascular mortality (nadir, 92 mm Hg). The hazard ratio for the primary cardiovascular outcome after adjustment for systolic blood pressure was 1.38 (95% CI, 1.18-1.62) for DBP <80 compared with DBP of 80 to 89.9 mm Hg (referrant), and the subdistribution hazard ratio after accounting for competing risk was 1.33 (1.17-1.51) compared with DBP ≥80 mm Hg. Cause-specific nonfatal outcome analyses showed a reverse J-shaped relationship for myocardial infarction, ischemic heart disease, and heart failure admissions but a U-shaped relationship for stroke admissions. Age-stratified analyses showed DBP had no independent effect on stroke admissions among the older patient subgroup (≥60 years of age), but the younger subgroup showed a clear U-shaped relationship. Intensive blood pressure reduction may lead to unintended consequences of higher healthcare utilization because of increased cardiovascular morbidity, and this merits future prospective studies. Low on-treatment DBP is associated with increased risk of noncardiovascular mortality, the reasons for which are unclear.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.119.12787DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6756261PMC
October 2019

Diagnosis and Management of Resistant Hypertension: A Case Report.

Hypertension 2019 11 19;74(5):1064-1067. Epub 2019 Aug 19.

From the Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Belgium (Z.-Y.Z., J.A.S.).

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http://dx.doi.org/10.1161/HYPERTENSIONAHA.119.13206DOI Listing
November 2019

Efficacy of a new single-pill combination of a thiazide-like diuretic and a calcium channel blocker (indapamide sustained release/amlodipine) in essential hypertension.

J Hypertens 2019 11;37(11):2280-2289

Foundation-Medical Research Institutes, Geneva, Switzerland.

Objectives: The current international, 12-week, double-blind, randomized, controlled trial assessed the efficacy and safety of indapamide sustained release/amlodipine single-pill combination (SPC) in mild-to-moderate hypertensive patients.

Methods: Following a 4-week run-in period on amlodipine 5 mg, patients (SBP 150-180 mmHg and/or DBP < 110 mmHg) were randomized to indapamide 1.5 mg sustained release/amlodipine 5 mg SPC or amlodipine 5 mg/valsartan 80 mg SPC with conditional uptitration at week 6. Office blood pressure (BP) was assessed at baseline, weeks 6 and 12; ambulatory and home blood pressure monitoring (ABPM/HBPM) at baseline and week 12.

Results: Baseline characteristics were similar in both groups (57 years, 51% men, BP 160/92 mmHg). 233 patients were randomized to IndSR/Aml and 232 to amlodipine/valsartan, of whom 48 and 57% were uptitrated, respectively. After 12 weeks, office SBP/DBP decreased similarly with both treatments (-21/-8 vs. -20/-8 mmHg) leading to BP control in 50% and BP response in 70% of patients. Uptitration was effective (P < 0.001) with both regimens, in favour of IndSR/Aml (SBP/DBP -12/-6 vs. -7/-3 mmHg, respectively). ABPM (n = 273) and HBPM (n = 194) confirmed 24-h efficacy of both regimens. In the subgroup of patients with sustained uncontrolled hypertension assessed by ABPM (n = 216), office SBP/DBP decreased by -23/-13 vs. -18/-10 mmHg, respectively (P = 0.016/P = 0.135, post-hoc analysis). Both treatments were generally well tolerated.

Conclusion: Both regimens produced effective BP reductions confirmed by ABPM/HBPM. Both treatments were well tolerated, in accordance with the individual agents' safety profile.

Trial Registration Number: EUDRA CT no. 2012-001690-84.
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http://dx.doi.org/10.1097/HJH.0000000000002177DOI Listing
November 2019

Effects of Calcium, Magnesium, and Potassium Concentrations on Ventricular Repolarization in Unselected Individuals.

J Am Coll Cardiol 2019 06;73(24):3118-3131

Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California.

Background: Subclinical changes on the electrocardiogram are risk factors for cardiovascular mortality. Recognition and knowledge of electrolyte associations in cardiac electrophysiology are based on only in vitro models and observations in patients with severe medical conditions.

Objectives: This study sought to investigate associations between serum electrolyte concentrations and changes in cardiac electrophysiology in the general population.

Methods: Summary results collected from 153,014 individuals (54.4% women; mean age 55.1 ± 12.1 years) from 33 studies (of 5 ancestries) were meta-analyzed. Linear regression analyses examining associations between electrolyte concentrations (mmol/l of calcium, potassium, sodium, and magnesium), and electrocardiographic intervals (RR, QT, QRS, JT, and PR intervals) were performed. The study adjusted for potential confounders and also stratified by ancestry, sex, and use of antihypertensive drugs.

Results: Lower calcium was associated with longer QT intervals (-11.5 ms; 99.75% confidence interval [CI]: -13.7 to -9.3) and JT duration, with sex-specific effects. In contrast, higher magnesium was associated with longer QT intervals (7.2 ms; 99.75% CI: 1.3 to 13.1) and JT. Lower potassium was associated with longer QT intervals (-2.8 ms; 99.75% CI: -3.5 to -2.0), JT, QRS, and PR durations, but all potassium associations were driven by use of antihypertensive drugs. No physiologically relevant associations were observed for sodium or RR intervals.

Conclusions: The study identified physiologically relevant associations between electrolytes and electrocardiographic intervals in a large-scale analysis combining cohorts from different settings. The results provide insights for further cardiac electrophysiology research and could potentially influence clinical practice, especially the association between calcium and QT duration, by which calcium levels at the bottom 2% of the population distribution led to clinically relevant QT prolongation by >5 ms.
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http://dx.doi.org/10.1016/j.jacc.2019.03.519DOI Listing
June 2019

Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions.

Am J Epidemiol 2019 06;188(6):1033-1054

Department of Epidemiology and Biostatistics, Imperial College London, London, United Kingdom.

A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups. Analyses covered the period July 2014-November 2017. Genetic main effects and interaction effects were jointly assessed by means of a 2-degrees-of-freedom (df) test, and a 1-df test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P < 1 × 10-6) with lipid levels in stage 1 and were evaluated in stage 2, followed by combined analyses of stage 1 and stage 2. In the combined analysis of stages 1 and 2, a total of 147 independent loci were associated with lipid levels at P < 5 × 10-8 using 2-df tests, of which 18 were novel. No genome-wide-significant associations were found testing the interaction effect alone. The novel loci included several genes (proprotein convertase subtilisin/kexin type 5 (PCSK5), vascular endothelial growth factor B (VEGFB), and apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (APOBEC1) complementation factor (A1CF)) that have a putative role in lipid metabolism on the basis of existing evidence from cellular and experimental models.
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http://dx.doi.org/10.1093/aje/kwz005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6545280PMC
June 2019
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