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1. Left ventricular hypertrophy as a risk factor for accelerated brain aging: Results from the Study of Health in Pomerania.

Author: Frenzel S, Bülow R, Dörr M, Felix SB, Friedrich N, Völzke H, Wittfeld K, Grabe HJ, and Bahls M
Subjects: Humans, Female, Middle Aged, Male, Risk Factors, Aging, Brain, Hypertrophy, Left Ventricular diagnostic imaging, Hypertrophy, Left Ventricular epidemiology, Hypertrophy, Left Ventricular etiology, Hypertension diagnostic imaging, Hypertension epidemiology
Abstract: Previous studies provided evidence for the importance of cardiac structure abnormalities, in particular greater left ventricular (LV) mass, for brain aging, but longitudinal studies are lacking to date. We included 926 individuals (median age 48 years; 53% women) from the TREND cohort of the Study of Health in Pomerania (SHIP) without reduced ejection fraction or a history of myocardial infarction. LV mass index (LVMI) was determined by echocardiography at baseline. Brain morphometric measurements were derived from magnetic resonance images at baseline and 7-year follow-up. Direct effects of baseline LVMI on brain morphometry at follow-up were estimated using linear regression models with adjustment for baseline brain morphometry. At baseline, median LVMI was 40 g/m 2.7 and 241 individuals (26%) met the criterion of LV hypertrophy. After correction for multiple testing, baseline LVMI was directly associated with reduced global cortical thickness and increased cortical brain age at follow-up independent from hypertension and blood pressure. Exposure-outcome relations were nonlinear and significantly stronger in the upper half of the exposure distribution. Specifically, an increase in baseline LVMI from the 50% quantile to the 95% quantile was associated additional 2.7 years (95% confidence interval = [1.5 years, 3.8 years]) of cortical brain age at follow-up. Additional regional analyses yielded bilateral effects on multiple frontal cortical regions. Our findings highlight the role of cardiac structure in brain aging. LVMI constitutes an easily measurable marker that might help to identify persons at risk for cognitive impairment and dementia., (© 2024 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)
Published: 2024
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2. The Correlation of Lung Function Parameters, Blood Pressure and Beta-Blocker Medication in a General Population.

Author: Schäper C, Ittermann T, Gläser S, Dörr M, Völzke H, Stubbe B, Felix SB, Ewert R, and Bollmann T
Subjects: Adrenergic beta-Antagonists pharmacology, Adrenergic beta-Antagonists therapeutic use, Adult, Blood Pressure, Humans, Lung, Antihypertensive Agents pharmacology, Antihypertensive Agents therapeutic use, Hypertension drug therapy, Hypertension epidemiology
Abstract: Objectives: Prior studies have investigated possible links between blood pressure, antihypertensive medication, especially beta-blockers and impairment of lung function. The aim of our study was to investigate an association between blood pressure, antihypertensive medication, focusing on beta-blockers, and its influence on lung function parameters in our adult population., Methods: From the two analysed cohorts of the population-based Study of Health in Pomerania (SHIP-1 and SHIP-TREND), pooled data for interview-based information, lung function variables including bodyplethysmography and blood pressure variables were used to perform adjusted linear regression analyses. Association analyses were conducted for the pooled population., Results: Within the whole pooled population we found some minor statistically significant interrelations in the multivariate analyses for blood pressure and lung function parameters. Statistical correlation between lung function and blood pressure were significant but too weak to be deemed clinically relevant.We also found interrelations between lung function and use of beta-blocker medication. Within the subgroup of individuals with antihypertensive medication containing beta-blockers compared to the reference group we found lower dynamic and static volumes e. g. for FEV1 (-70 ml), FVC (-90 ml), a reduction of TLC (-130 ml) and ITGV (-100 ml), however we did not find an increase in airway resistance (Rtot)., Conclusion: Based on the data of SHIP-1 and SHIP TREND our results confirm a minor association between blood pressure and lung function. More importantly, we have seen a significant decrease of lung volumes for hypertensive patients with beta- blocker medication as described in literature before. To the best of our knowledge, we are the first to examine the interrelation between blood pressure, medication and lung function in an epidemiological study using data of spirometry, body plethysmography and CO transfer., Competing Interests: The authors do not report any conflicts of interest., (Thieme. All rights reserved.)
Published: 2022
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3. Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals.

Author: Surendran P, Feofanova EV, Lahrouchi N, Ntalla I, Karthikeyan S, Cook J, Chen L, Mifsud B, Yao C, Kraja AT, Cartwright JH, Hellwege JN, Giri A, Tragante V, Thorleifsson G, Liu DJ, Prins BP, Stewart ID, Cabrera CP, Eales JM, Akbarov A, Auer PL, Bielak LF, Bis JC, Braithwaite VS, Brody JA, Daw EW, Warren HR, Drenos F, Nielsen SF, Faul JD, Fauman EB, Fava C, Ferreira T, Foley CN, Franceschini N, Gao H, Giannakopoulou O, Giulianini F, Gudbjartsson DF, Guo X, Harris SE, Havulinna AS, Helgadottir A, Huffman JE, Hwang SJ, Kanoni S, Kontto J, Larson MG, Li-Gao R, Lindström J, Lotta LA, Lu Y, Luan J, Mahajan A, Malerba G, Masca NGD, Mei H, Menni C, Mook-Kanamori DO, Mosen-Ansorena D, Müller-Nurasyid M, Paré G, Paul DS, Perola M, Poveda A, Rauramaa R, Richard M, Richardson TG, Sepúlveda N, Sim X, Smith AV, Smith JA, Staley JR, Stanáková A, Sulem P, Thériault S, Thorsteinsdottir U, Trompet S, Varga TV, Velez Edwards DR, Veronesi G, Weiss S, Willems SM, Yao J, Young R, Yu B, Zhang W, Zhao JH, Zhao W, Zhao W, Evangelou E, Aeschbacher S, Asllanaj E, Blankenberg S, Bonnycastle LL, Bork-Jensen J, Brandslund I, Braund PS, Burgess S, Cho K, Christensen C, Connell J, Mutsert R, Dominiczak AF, Dörr M, Eiriksdottir G, Farmaki AE, Gaziano JM, Grarup N, Grove ML, Hallmans G, Hansen T, Have CT, Heiss G, Jørgensen ME, Jousilahti P, Kajantie E, Kamat M, Käräjämäki A, Karpe F, Koistinen HA, Kovesdy CP, Kuulasmaa K, Laatikainen T, Lannfelt L, Lee IT, Lee WJ, Linneberg A, Martin LW, Moitry M, Nadkarni G, Neville MJ, Palmer CNA, Papanicolaou GJ, Pedersen O, Peters J, Poulter N, Rasheed A, Rasmussen KL, Rayner NW, Mägi R, Renström F, Rettig R, Rossouw J, Schreiner PJ, Sever PS, Sigurdsson EL, Skaaby T, Sun YV, Sundstrom J, Thorgeirsson G, Esko T, Trabetti E, Tsao PS, Tuomi T, Turner ST, Tzoulaki I, Vaartjes I, Vergnaud AC, Willer CJ, Wilson PWF, Witte DR, Yonova-Doing E, Zhang H, Aliya N, Almgren P, Amouyel P, Asselbergs FW, Barnes MR, Blakemore AI, Boehnke M, Bots ML, Bottinger EP, Buring JE, Chambers JC, Chen YI, Chowdhury R, Conen D, Correa A, Davey Smith G, Boer RA, Deary IJ, Dedoussis G, Deloukas P, Di Angelantonio E, Elliott P, Felix SB, Ferrières J, Ford I, Fornage M, Franks PW, Franks S, Frossard P, Gambaro G, Gaunt TR, Groop L, Gudnason V, Harris TB, Hayward C, Hennig BJ, Herzig KH, Ingelsson E, Tuomilehto J, Järvelin MR, Jukema JW, Kardia SLR, Kee F, Kooner JS, Kooperberg C, Launer LJ, Lind L, Loos RJF, Majumder AAS, Laakso M, McCarthy MI, Melander O, Mohlke KL, Murray AD, Nordestgaard BG, Orho-Melander M, Packard CJ, Padmanabhan S, Palmas W, Polasek O, Porteous DJ, Prentice AM, Province MA, Relton CL, Rice K, Ridker PM, Rolandsson O, Rosendaal FR, Rotter JI, Rudan I, Salomaa V, Samani NJ, Sattar N, Sheu WH, Smith BH, Soranzo N, Spector TD, Starr JM, Sebert S, Taylor KD, Lakka TA, Timpson NJ, Tobin MD, van der Harst P, van der Meer P, Ramachandran VS, Verweij N, Virtamo J, Völker U, Weir DR, Zeggini E, Charchar FJ, Wareham NJ, Langenberg C, Tomaszewski M, Butterworth AS, Caulfield MJ, Danesh J, Edwards TL, Holm H, Hung AM, Lindgren CM, Liu C, Manning AK, Morris AP, Morrison AC, O'Donnell CJ, Psaty BM, Saleheen D, Stefansson K, Boerwinkle E, Chasman DI, Levy D, Newton-Cheh C, Munroe PB, and Howson JMM
Subjects: GATA5 Transcription Factor genetics, Genome-Wide Association Study, Genotype, Humans, Mutation genetics, Phospholipase C beta genetics, Polymorphism, Single Nucleotide genetics, Blood Pressure genetics, Gene Frequency genetics, Genetic Predisposition to Disease genetics, Hypertension genetics
Abstract: 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 -8 ), 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.
Published: 2020
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4. [Blood pressure measurement in the NAKO German National Cohort (GNC) - differences in methods, distribution of blood pressure values, and awareness of hypertension compared to other population-based studies in Germany].

Author: Schikowski T, Wigmann C, Fuks KB, Schipf S, Heier M, Neuhauser H, Sarganas G, Ahrens W, Becher H, Berger K, Brenner H, Castell S, Damms-Machado A, Dörr M, Ebert N, Efremov L, Emmel C, Felix SB, Fischer B, Franzke CW, Gastell S, Günther K, Haerting J, Ittermann T, Jaeschke L, Jagodzinski A, Jöckel KH, Kaaks R, Kalinowski S, Keil T, Kemmling Y, Kluttig A, Krist L, Kuss O, Legath N, Leitzmann M, Lieb W, Löffler M, Meinke-Franze C, Michels KB, Mikolajczyk R, Moebus S, Nuding S, Peters A, Pischon T, Rückert-Eheberg IM, Schöttker B, Schmidt B, Schmidt CO, Schulze MB, Stang A, Thiele I, Thierry S, Thorand B, Völzke H, Waniek S, Werdan K, Wirkner K, and Greiser KH
Subjects: Cohort Studies, Germany, Humans, Population Surveillance, Blood Pressure, Hypertension
Published: 2020
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5. Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries.

Author: Feitosa MF, Kraja AT, Chasman DI, Sung YJ, Winkler TW, Ntalla I, Guo X, Franceschini N, Cheng CY, Sim X, Vojinovic D, Marten J, Musani SK, Li C, Bentley AR, Brown MR, Schwander K, Richard MA, Noordam R, Aschard H, Bartz TM, Bielak LF, Dorajoo R, Fisher V, Hartwig FP, Horimoto ARVR, Lohman KK, Manning AK, Rankinen T, Smith AV, Tajuddin SM, Wojczynski MK, Alver M, Boissel M, Cai Q, Campbell A, Chai JF, Chen X, Divers J, Gao C, Goel A, Hagemeijer Y, Harris SE, He M, Hsu FC, Jackson AU, Kähönen M, Kasturiratne A, Komulainen P, Kühnel B, Laguzzi F, Luan J, Matoba N, Nolte IM, Padmanabhan S, Riaz M, Rueedi R, Robino A, Said MA, Scott RA, Sofer T, Stančáková A, Takeuchi F, Tayo BO, van der Most PJ, Varga TV, Vitart V, Wang Y, Ware EB, Warren HR, Weiss S, Wen W, Yanek LR, Zhang W, Zhao JH, Afaq S, Amin N, Amini M, Arking DE, Aung T, Boerwinkle E, Borecki I, Broeckel U, Brown M, Brumat M, Burke GL, Canouil M, Chakravarti A, Charumathi S, Ida Chen YD, Connell JM, Correa A, de las Fuentes L, de Mutsert R, de Silva HJ, Deng X, Ding J, Duan Q, Eaton CB, Ehret G, Eppinga RN, Evangelou E, Faul JD, Felix SB, Forouhi NG, Forrester T, Franco OH, Friedlander Y, Gandin I, Gao H, Ghanbari M, Gigante B, Gu CC, Gu D, Hagenaars SP, Hallmans G, Harris TB, He J, Heikkinen S, Heng CK, Hirata M, Howard BV, Ikram MA, John U, Katsuya T, Khor CC, Kilpeläinen TO, Koh WP, Krieger JE, Kritchevsky SB, Kubo M, Kuusisto J, Lakka TA, Langefeld CD, Langenberg C, Launer LJ, Lehne B, Lewis CE, Li Y, Lin S, Liu J, Liu J, Loh M, Louie T, Mägi R, McKenzie CA, Meitinger T, Metspalu A, Milaneschi Y, Milani L, Mohlke KL, Momozawa Y, Nalls MA, Nelson CP, Sotoodehnia N, Norris JM, O'Connell JR, Palmer ND, Perls T, Pedersen NL, Peters A, Peyser PA, Poulter N, Raffel LJ, Raitakari OT, Roll K, Rose LM, Rosendaal FR, Rotter JI, Schmidt CO, Schreiner PJ, Schupf N, Scott WR, Sever PS, Shi Y, Sidney S, Sims M, Sitlani CM, Smith JA, Snieder H, Starr JM, Strauch K, Stringham HM, Tan NYQ, Tang H, Taylor KD, Teo YY, Tham YC, Turner ST, Uitterlinden AG, Vollenweider P, Waldenberger M, Wang L, Wang YX, Wei WB, Williams C, Yao J, Yu C, Yuan JM, Zhao W, Zonderman AB, Becker DM, Boehnke M, Bowden DW, Chambers JC, Deary IJ, Esko T, Farrall M, Franks PW, Freedman BI, Froguel P, Gasparini P, Gieger C, Jonas JB, Kamatani Y, Kato N, Kooner JS, Kutalik Z, Laakso M, Laurie CC, Leander K, Lehtimäki T, Study LC, Magnusson PKE, Oldehinkel AJ, Penninx BWJH, Polasek O, Porteous DJ, Rauramaa R, Samani NJ, Scott J, Shu XO, van der Harst P, Wagenknecht LE, Wareham NJ, Watkins H, Weir DR, Wickremasinghe AR, Wu T, Zheng W, Bouchard C, Christensen K, Evans MK, Gudnason V, Horta BL, Kardia SLR, Liu Y, Pereira AC, Psaty BM, Ridker PM, van Dam RM, Gauderman WJ, Zhu X, Mook-Kanamori DO, Fornage M, Rotimi CN, Cupples LA, Kelly TN, Fox ER, Hayward C, van Duijn CM, Tai ES, Wong TY, Kooperberg C, Palmas W, Rice K, Morrison AC, Elliott P, Caulfield MJ, Munroe PB, Rao DC, Province MA, and Levy D
Subjects: Adolescent, Adult, Aged, Aged, 80 and over, Cohort Studies, Female, Gene-Environment Interaction, Genetic Predisposition to Disease epidemiology, Genetic Predisposition to Disease genetics, Genome-Wide Association Study, Humans, Male, Middle Aged, Pedigree, Young Adult, Alcohol Drinking epidemiology, Alcohol Drinking genetics, Blood Pressure genetics, Hypertension epidemiology, Hypertension genetics, Polymorphism, Single Nucleotide, Racial Groups genetics, Racial Groups statistics & numerical data
Abstract: Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in ≈131K individuals across several ancestry groups yielded 3,514 SNVs (245 loci) with suggestive evidence of association (P < 1.0 x 10-5). In Stage 2, these SNVs were tested for independent external replication in ≈440K individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2,159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 x 10-8). For African ancestry samples, we detected 18 potentially novel BP loci (P < 5.0 x 10-8) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2) have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension., Competing Interests: The authors have read the journal's policy and the authors of this manuscript have the following competing interests: Bruce M. Psaty (BMP) serves on the DSMB of a clinical trial funded by Zoll Lifecor and on the Steering Committee of the Yale Open Data Access Project funded by Johnson & Johnson. Barbara V. Howard (BVH) has a contract from National Heart, Lung, and Blood Institute (NHLBI). Brenda W.J.H. Penninx (BWJHP) has received research funding (non-related to the work reported here) from Jansen Research and Boehringer Ingelheim. Mike A. Nalls (MAN) is supported by a consulting contract between Data Tecnica International LLC and the National Institute on Aging (NIA), National Institutes of Health (NIH), Bethesda, MD, USA. MAN also consults for Illumina Inc., the Michael J. Fox Foundation, and the University of California Healthcare. MAN also has commercial affiliation with Data Tecnica International, Glen Echo, MD, USA. Mark J. Caulfield (MJC) has commercial affiliation and is Chief Scientist for Genomics England, a UK government company. OHF is supported by grants from Metagenics (on women's health and epigenetics) and from Nestlé (on child health). Peter S. Sever (PSS) is financial supported from several pharmaceutical companies which manufacture either blood pressure lowering or lipid lowering agents, or both, and consultancy fees. Paul W. Franks (PWF) has been a paid consultant in the design of a personalized nutrition trial (PREDICT) as part of a private-public partnership at Kings College London, UK, and has received research support from several pharmaceutical companies as part of European Union Innovative Medicines Initiative (IMI) projects. Terho Lehtimäki (TL) is employed by Fimlab Ltd. Ozren Polašek (OP) is employed by Gen‐info Ltd. There are no patents, products in development, or marked products to declare. All the other authors have declared no competing interests exist. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.
Published: 2018
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6. Transcriptome-Wide Analysis Identifies Novel Associations With Blood Pressure.

Author: Zeller T, Schurmann C, Schramm K, Müller C, Kwon S, Wild PS, Teumer A, Herrington D, Schillert A, Iacoviello L, Kratzer A, Jagodzinski A, Karakas M, Ding J, Neumann JT, Kuulasmaa K, Gieger C, Kacprowski T, Schnabel RB, Roden M, Wahl S, Rotter JI, Ojeda F, Carstensen-Kirberg M, Tregouet DA, Dörr M, Meitinger T, Lackner KJ, Wolf P, Felix SB, Landmesser U, Costanzo S, Ziegler A, Liu Y, Völker U, Palmas W, Prokisch H, Guo X, Herder C, Blankenberg S, and Homuth G
Subjects: Adult, Blood Pressure genetics, Blood Pressure Determination methods, Blood Pressure Determination statistics & numerical data, CCAAT-Enhancer-Binding Proteins genetics, Female, Gene Expression, Gene Expression Profiling, Genome-Wide Association Study, Humans, Male, Myelin and Lymphocyte-Associated Proteolipid Proteins genetics, Nucleoside Transport Proteins, Poly(ADP-ribose) Polymerases genetics, Polymorphism, Single Nucleotide, Risk Factors, Transcription Factors genetics, Carrier Proteins genetics, Hypertension diagnosis, Hypertension genetics, LIM Domain Proteins genetics, Stroke epidemiology, Stroke etiology, Stroke prevention & control
Abstract: Hypertension represents a major cardiovascular risk factor. The pathophysiology of increased blood pressure (BP) is not yet completely understood. Transcriptome profiling offers possibilities to uncover genetics effects on BP. Based on 2 populations including 2549 individuals, a meta-analyses of monocytic transcriptome-wide profiles were performed to identify transcripts associated with BP. Replication was performed in 2 independent studies of whole-blood transcriptome data including 1990 individuals. For identified candidate genes, a direct link between long-term changes in BP and gene expression over time and by treatment with BP-lowering therapy was assessed. The predictive value of protein levels encoded by candidate genes for subsequent cardiovascular disease was investigated. Eight transcripts ( CRIP1 , MYADM , TIPARP , TSC22D3 , CEBPA , F12, LMNA , and TPPP3 ) were identified jointly accounting for up to 13% (95% confidence interval, 8.7-16.2) of BP variability. Changes in CRIP1 , MYADM , TIPARP , LMNA , TSC22D3 , CEBPA , and TPPP3 expression associated with BP changes-among these, CRIP1 gene expression was additionally correlated to measures of cardiac hypertrophy. Assessment of circulating CRIP1 (cystein-rich protein 1) levels as biomarkers showed a strong association with increased risk for incident stroke (hazard ratio, 1.06; 95% confidence interval, 1.03-1.09; P =5.0×10 -5 ). Our comprehensive analysis of global gene expression highlights 8 novel transcripts significantly associated with BP, providing a link between gene expression and BP. Translational approaches further established evidence for the potential use of CRIP1 as emerging disease-related biomarker., (© 2017 American Heart Association, Inc.)
Published: 2017
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7. Genetic Interactions with Age, Sex, Body Mass Index, and Hypertension in Relation to Atrial Fibrillation: The AFGen Consortium.

Author: Weng LC, Lunetta KL, Müller-Nurasyid M, Smith AV, Thériault S, Weeke PE, Barnard J, Bis JC, Lyytikäinen LP, Kleber ME, Martinsson A, Lin HJ, Rienstra M, Trompet S, Krijthe BP, Dörr M, Klarin D, Chasman DI, Sinner MF, Waldenberger M, Launer LJ, Harris TB, Soliman EZ, Alonso A, Paré G, Teixeira PL, Denny JC, Shoemaker MB, Van Wagoner DR, Smith JD, Psaty BM, Sotoodehnia N, Taylor KD, Kähönen M, Nikus K, Delgado GE, Melander O, Engström G, Yao J, Guo X, Christophersen IE, Ellinor PT, Geelhoed B, Verweij N, Macfarlane P, Ford I, Heeringa J, Franco OH, Uitterlinden AG, Völker U, Teumer A, Rose LM, Kääb S, Gudnason V, Arking DE, Conen D, Roden DM, Chung MK, Heckbert SR, Benjamin EJ, Lehtimäki T, März W, Smith JG, Rotter JI, van der Harst P, Jukema JW, Stricker BH, Felix SB, Albert CM, and Lubitz SA
Subjects: Age Factors, Aged, Chromosomes, Human, Pair 4 genetics, Female, Genetic Loci, Genome-Wide Association Study, Humans, Male, Middle Aged, Odds Ratio, Polymorphism, Single Nucleotide genetics, Reproducibility of Results, Risk Factors, Atrial Fibrillation genetics, Body Mass Index, Epistasis, Genetic, Genetic Predisposition to Disease, Hypertension genetics, Sex Characteristics
Abstract: It is unclear whether genetic markers interact with risk factors to influence atrial fibrillation (AF) risk. We performed genome-wide interaction analyses between genetic variants and age, sex, hypertension, and body mass index in the AFGen Consortium. Study-specific results were combined using meta-analysis (88,383 individuals of European descent, including 7,292 with AF). Variants with nominal interaction associations in the discovery analysis were tested for association in four independent studies (131,441 individuals, including 5,722 with AF). In the discovery analysis, the AF risk associated with the minor rs6817105 allele (at the PITX2 locus) was greater among subjects ≤ 65 years of age than among those > 65 years (interaction p-value = 4.0 × 10 -5 ). The interaction p-value exceeded genome-wide significance in combined discovery and replication analyses (interaction p-value = 1.7 × 10 -8 ). We observed one genome-wide significant interaction with body mass index and several suggestive interactions with age, sex, and body mass index in the discovery analysis. However, none was replicated in the independent sample. Our findings suggest that the pathogenesis of AF may differ according to age in individuals of European descent, but we did not observe evidence of statistically significant genetic interactions with sex, body mass index, or hypertension on AF risk.
Published: 2017
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8. Hypertension in Germany.

Author: Neuhauser H, Diederichs C, Boeing H, Felix SB, Jünger C, Lorbeer R, Meisinger C, Peters A, Völzke H, Weikert C, Wild P, and Dörr M
Subjects: Adult, Aged, Blood Pressure, Female, Germany epidemiology, Health Surveys, Humans, Male, Middle Aged, Prevalence, Hypertension epidemiology
Abstract: Background: Hypertension is a key risk factor. However, population data based on blood pressure measurements in Germany are scarce., Methods: Standardized blood pressure (BP) measurements and medication data from seven population-based studies conducted in Germany between 1994 and 2012 (66 845 participants, 25-74 years) were analyzed: the EPICPotsdam study (1994-1998, EPIC), the KORA-S4 Study (1999-2001) in Augsburg, and the Gutenberg Health Study (2007-2012, GHS) in Mainz/Mainz-Bingen provided data for descriptive comparisons. Time trends were analyzed based on identical study regions for the German National Health Interview and Examination Survey 1998 (BGS98) and the German Health Examination Survey for Adults (2008-11, DEGS1) as well as the Study of Health in Pomerania (SHIP) in Northeast Germany (1997-2001) and the SHIP-TREND study (2008-2012). BP data were adjusted for study-specific measurement devices based on calibration studies., Results: After adjustment for study-specific measurement devices, mean systolic and diastolic BP values were lower and treatment proportions higher in recent (2007-2012) compared to older (1994-2001) studies. Mean BP decrease was most pronounced (systolic ≥ 10 mmHg) in the elderly (55-74 years). The regional SHIP-TREND data for Northeast Germany showed a decrease in mean systolic BP in young men aged 25 to 34 years; on a national level according to the DEGS1 data, however, no such decrease was observed for this group., Conclusion: New data add evidence for lower BP in Germany. However, the prevention potential remains high. Future research based on population-based data should place a special focus on blood pressure data in young men.
Published: 2016
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9. Assessing cutoff values for increased exercise blood pressure to predict incident hypertension in a general population.

Author: Lorbeer R, Ittermann T, Völzke H, Gläser S, Ewert R, Felix SB, and Dörr M
Subjects: Adult, Aged, Exercise Test, Female, Humans, Male, Middle Aged, ROC Curve, Risk Factors, Blood Pressure physiology, Exercise, Hypertension epidemiology, Hypertension physiopathology
Abstract: Objective: Cutoff values for increased exercise blood pressure (BP) are not established in hypertension guidelines. The aim of the study was to assess optimal cutoff values for increased exercise BP to predict incident hypertension., Methods: Data of 661 normotensive participants (386 women) aged 25-77 years from the Study of Health in Pomerania (SHIP-1) with a 5-year follow-up were used. Exercise BP was measured at a submaximal level of 100 W and at maximum level of a symptom-limited cycle ergometry test. Cutoff values for increased exercise BP were defined at the maximum sum of sensitivity and specificity for the prediction of incident hypertension. The area under the receiver-operating characteristic curve (AUC) and net reclassification index (NRI) were calculated to investigate whether increased exercise BP adds predictive value for incident hypertension beyond established cardiovascular risk factors., Results: In men, values of 160 mmHg (100 W level; AUC = 0.7837; NRI = 0.534, P < 0.001) and 210 mmHg (maximum level; AUC = 0.7677; NRI = 0.340, P = 0.003) were detected as optimal cutoff values for the definition of increased exercise SBP. A value of 190 mmHg (AUC = 0.8347; NRI = 0.519, P < 0.001) showed relevance for the definition of increased exercise SBP in women at the maximum level., Conclusion: According to our analyses, 190 and 210 mmHg are clinically relevant cutoff values for increased exercise SBP at the maximum exercise level of cycle ergometry test for women and men, respectively. In addition, for men, our analyses provided a cutoff value of 160 mmHg for increased exercise SBP at the 100 W level.
Published: 2015
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10. A meta-analysis of gene expression signatures of blood pressure and hypertension.

Author: Huan T, Esko T, Peters MJ, Pilling LC, Schramm K, Schurmann C, Chen BH, Liu C, Joehanes R, Johnson AD, Yao C, Ying SX, Courchesne P, Milani L, Raghavachari N, Wang R, Liu P, Reinmaa E, Dehghan A, Hofman A, Uitterlinden AG, Hernandez DG, Bandinelli S, Singleton A, Melzer D, Metspalu A, Carstensen M, Grallert H, Herder C, Meitinger T, Peters A, Roden M, Waldenberger M, Dörr M, Felix SB, Zeller T, Vasan R, O'Donnell CJ, Munson PJ, Yang X, Prokisch H, Völker U, van Meurs JB, Ferrucci L, and Levy D
Subjects: Gene Expression Regulation, Genetic Predisposition to Disease, Genotype, Humans, Hypertension pathology, Polymorphism, Single Nucleotide, Blood Pressure genetics, Genome-Wide Association Study, Hypertension genetics, Transcriptome genetics
Abstract: Genome-wide association studies (GWAS) have uncovered numerous genetic variants (SNPs) that are associated with blood pressure (BP). Genetic variants may lead to BP changes by acting on intermediate molecular phenotypes such as coded protein sequence or gene expression, which in turn affect BP variability. Therefore, characterizing genes whose expression is associated with BP may reveal cellular processes involved in BP regulation and uncover how transcripts mediate genetic and environmental effects on BP variability. A meta-analysis of results from six studies of global gene expression profiles of BP and hypertension in whole blood was performed in 7017 individuals who were not receiving antihypertensive drug treatment. We identified 34 genes that were differentially expressed in relation to BP (Bonferroni-corrected p<0.05). Among these genes, FOS and PTGS2 have been previously reported to be involved in BP-related processes; the others are novel. The top BP signature genes in aggregate explain 5%-9% of inter-individual variance in BP. Of note, rs3184504 in SH2B3, which was also reported in GWAS to be associated with BP, was found to be a trans regulator of the expression of 6 of the transcripts we found to be associated with BP (FOS, MYADM, PP1R15A, TAGAP, S100A10, and FGBP2). Gene set enrichment analysis suggested that the BP-related global gene expression changes include genes involved in inflammatory response and apoptosis pathways. Our study provides new insights into molecular mechanisms underlying BP regulation, and suggests novel transcriptomic markers for the treatment and prevention of hypertension.
Published: 2015
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11. A new, accurate predictive model for incident hypertension.

Author: Völzke H, Fung G, Ittermann T, Yu S, Baumeister SE, Dörr M, Lieb W, Völker U, Linneberg A, Jørgensen T, Felix SB, Rettig R, Rao B, and Kroemer HK
Subjects: Adult, Age Factors, Aged, Algorithms, Bayes Theorem, Female, Germany epidemiology, Humans, Hypertension etiology, Male, Middle Aged, Models, Theoretical, ROC Curve, Random Allocation, Risk Assessment, Risk Factors, Young Adult, Data Mining, Hypertension epidemiology
Abstract: Objective: Data mining represents an alternative approach to identify new predictors of multifactorial diseases. This work aimed at building an accurate predictive model for incident hypertension using data mining procedures., Methods: The primary study population consisted of 1605 normotensive individuals aged 20-79 years with 5-year follow-up from the population-based study, that is the Study of Health in Pomerania (SHIP). The initial set was randomly split into a training and a testing set. We used a probabilistic graphical model applying a Bayesian network to create a predictive model for incident hypertension and compared the predictive performance with the established Framingham risk score for hypertension. Finally, the model was validated in 2887 participants from INTER99, a Danish community-based intervention study., Results: In the training set of SHIP data, the Bayesian network used a small subset of relevant baseline features including age, mean arterial pressure, rs16998073, serum glucose and urinary albumin concentrations. Furthermore, we detected relevant interactions between age and serum glucose as well as between rs16998073 and urinary albumin concentrations [area under the receiver operating characteristic (AUC 0.76)]. The model was confirmed in the SHIP validation set (AUC 0.78) and externally replicated in INTER99 (AUC 0.77). Compared to the established Framingham risk score for hypertension, the predictive performance of the new model was similar in the SHIP validation set and moderately better in INTER99., Conclusion: Data mining procedures identified a predictive model for incident hypertension, which included innovative and easy-to-measure variables. The findings promise great applicability in screening settings and clinical practice.
Published: 2013
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12. Molecular changes in the early phase of renin-dependent cardiac hypertrophy in hypertensive cyp1a1ren-2 transgenic rats.

Author: Kunert-Keil C, Landsberger M, Jantzen F, Niessner F, Kroemer HK, Felix SB, Brinkmeier H, and Peters J
Subjects: Action Potentials genetics, Animals, Calcium metabolism, Calcium Channels metabolism, Cardiomegaly pathology, Cell Nucleus metabolism, GATA4 Transcription Factor metabolism, Gene Expression Regulation, Heart Ventricles metabolism, Heart Ventricles pathology, Homeostasis genetics, Hypertension pathology, Myocytes, Cardiac metabolism, Myocytes, Cardiac pathology, NFATC Transcription Factors metabolism, Protein Transport, RNA, Messenger genetics, RNA, Messenger metabolism, Rats, Rats, Transgenic, Sarcoplasmic Reticulum Calcium-Transporting ATPases metabolism, Transient Receptor Potential Channels genetics, Transient Receptor Potential Channels metabolism, Cardiomegaly complications, Cardiomegaly metabolism, Cytochrome P-450 CYP1A1 metabolism, Hypertension complications, Hypertension metabolism, Renin metabolism
Abstract: An early response to high arterial pressure is the development of cardiac hypertrophy. Functional and transcriptional regulation of ion channels and Ca(2+) handling proteins are involved in this process but the relative contribution of each is unclear. In this study, we investigated the expression of genes involved in action potential generation and Ca(2+) homeostasis of cardiomyocytes in hypertensive cyp1a1ren-2 transgenic rats. In this model, the transgene prorenin was induced by indole-3-carbinol for 2 weeks allowing the induction of hypertension. Electrophysiological recordings from cardiomyocytes of hypertensive rats revealed a slight increase in membrane capacitance consistent with cellular hypertrophy. L-type calcium current density was reduced by 30%. Left ventricles of hypertensive rats showed a significant increase in transcript and protein levels of the cation channel TRPC6 and FK506-binding protein, whereas levels of SERCA2 and voltage-dependent potassium channels K(v)4.2 and K(v)4.3 were found to be decreased. Further, a marked nuclear localization of the transcription factors GATA4 and NFATC4 was observed in cardiac tissue of hypertensive rats. The cyp1a1ren-2 transgenic rat thus appears to be a valid model to investigate early changes in cardiac hypertrophy. This study points to roles for TRPC6, FK506BP, SERCA2, K(v)4.2, and K(v)4.3 in the development of cardiac hypertrophy.
Published: 2013
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13. Quinaprilat: a review of its pharmacokinetics, pharmacodynamics, toxicological data and clinical application.

Author: Kieback AG, Felix SB, and Reffelmann T
Subjects: Angiotensin-Converting Enzyme Inhibitors adverse effects, Angiotensin-Converting Enzyme Inhibitors pharmacokinetics, Animals, Clinical Trials as Topic, Drug Evaluation, Preclinical, Female, Half-Life, Heart Failure drug therapy, Heart Failure physiopathology, Humans, Hypertension physiopathology, Pregnancy, Tetrahydroisoquinolines adverse effects, Tetrahydroisoquinolines pharmacokinetics, Angiotensin-Converting Enzyme Inhibitors therapeutic use, Hypertension drug therapy, Tetrahydroisoquinolines therapeutic use
Abstract: Background: Quinaprilat is an ACE inhibitor for intravenous use especially in patients with arterial hypertension or chronic heart failure. In contrast to the oral prodrug quinapril, it has not been approved for clinical application., Objective: In this review, the pharmacokinetic and pharmacodynamic profile of quinaprilat as well as toxicological data and results of preclinical and clinical studies are summarized., Methods: In a PubMed search for the terms "quinaprilat" and "quinapril", literature relevant for this review was selected., Results: Quinaprilat is a potent nonsulfhydryl selective ACE inhibitor with a short elimination half-life of 2 - 3 h, but due to slow dissociation from tissue ACE, once daily dosing is sufficient for effective ACE inhibition. Quinaprilat is excreted mainly in urine. In long-term animal studies, quinaprilat was not teratogenic, mutagenic or carcinogenic. However, due to the risk of fetal and neonatal morbidity and death, it should not be administrated in pregnancy. Quinaprilat is characterized by an excellent safety profile; adverse events occur infrequently and are rarely serious., Conclusion: Quinaprilat is an attractive ACE inhibitor, which potently inhibits tissue ACE.
Published: 2009
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14. The association between subclinical hyperthyroidism and blood pressure in a population-based study.

Author: Völzke H, Alte D, Dörr M, Wallaschofski H, John U, Felix SB, and Rettig R
Subjects: Adult, Age Factors, Aged, Case-Control Studies, Cross-Sectional Studies, Female, Health Surveys, Humans, Hypertension blood, Hyperthyroidism blood, Male, Middle Aged, Risk Assessment, Risk Factors, Thyrotropin blood, Hypertension epidemiology, Hyperthyroidism complications
Abstract: Objective: Although evidence for an increased risk of hypertension in both overt hyperthyroidism and overt hypothyroidism is consistent, the relation between subclinical hyperthyroidism and blood pressure has not yet received sufficient attention., Methods: The Study of Health in Pomerania is a population-based survey in Germany that was conducted in a previously iodine-deficient region. A study population of 4087 subjects (2050 women) without overt hyperthyroidism or increased serum thyrotropin levels was available for the present study. Serum thyrotropin levels < 0.25 mIU/l and < 0.1 mIU/l were considered decreased and suppressed, respectively., Results: Multivariable analyses revealed lower adjusted mean values for systolic blood pressure in subjects with decreased [132.9 mmHg, 95% confidence interval (CI) = 131.1 mmHg; 134.8 mmHg] versus normal serum thyrotropin levels (135.0 mmHg, 95% CI = 134.4 mmHg; 135.6 mmHg, P = 0.04). The adjusted mean values for diastolic blood pressure and pulse pressure did not differ significantly between both groups. Analyses that were performed after all subjects receiving antihypertensive medications had been excluded did not reveal any statistically significant associations between decreased serum thyrotropin levels and the endpoints investigated. There was also no association of suppressed serum thyrotropin levels with blood pressure or hypertension., Conclusion: It is concluded that subclinical hyperthyroidism, as demonstrated by decreased as well as suppressed serum thyrotropin levels and serum free thyroid hormone levels within the reference range, is not associated with hypertension.
Published: 2006
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15. Gender differences in the relation between number of teeth and systolic blood pressure.

Author: Völzke H, Schwahn C, Dörr M, Schwarz S, Robinson D, Dören M, Rettig R, Felix SB, John U, and Kocher T
Subjects: Adult, Aged, Antihypertensive Agents therapeutic use, Female, Germany epidemiology, Humans, Hypertension drug therapy, Male, Middle Aged, Regression Analysis, Risk Factors, Sex Factors, Tooth Loss physiopathology, Blood Pressure physiology, Hypertension epidemiology, Tooth Loss epidemiology
Abstract: Background: Tooth loss predicts total and circulatory mortality. The reasons for the increased mortality in subjects with a low number of teeth may be related to enhanced atherosclerosis, elevated arterial pressure and more frequent hypertension. The present study was designed to investigate whether there is an association between the number of teeth and arterial pressure or hypertension., Methods: We used data of 4185 adult subjects (2150 women) collected for the population-based Study of Health in Pomerania. The number of teeth was counted by trained and certified dentists. Hypertension was defined as systolic blood pressure >or= 140 mmHg or diastolic blood pressure >or= 90 mmHg or use of antihypertensive medication. Multivariable analyses were adjusted for relevant confounders., Results: The adjusted mean (standard error) systolic blood pressure in men having 0-6 teeth was 149.6 mmHg (1.3 mmHg) compared to 142.6 mmHg (1.2 mmHg) in men having 27-28 teeth (P < 0.05). The adjusted odds for hypertension in men with 0-6 teeth compared to men with 27-28 teeth were 1.91 (95% confidence interval 1.21; 3.02, P < 0.05). In women no such relations were found., Conclusion: There is an inverse association between the number of teeth and systolic blood pressure and hypertension in men but not in women. The present findings partly explain the relation between tooth loss and mortality.
Published: 2006
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16. Endothelial nitric oxide synthase Glu298Asp gene polymorphism, blood pressure and hypertension in a general population sample.

Author: Wolff B, Grabe HJ, Schlüter C, Popowski K, Völzke H, Lüdemann J, John U, Felix SB, and Cascorbi I
Subjects: Adult, Aged, Cohort Studies, Cross-Sectional Studies, Female, Germany epidemiology, Humans, Hypertension epidemiology, Hypertension genetics, Male, Middle Aged, Multivariate Analysis, Nitric Oxide Synthase Type III, Odds Ratio, Prevalence, Aspartic Acid metabolism, Blood Pressure physiology, Endothelium, Vascular enzymology, Hypertension enzymology, Nitric Oxide Synthase genetics, Polymorphism, Genetic
Abstract: Objective: The Glu298Asp (E/D) polymorphism of the endothelial nitric oxide synthase (eNOS) gene has been related to hypertension. Since several studies have produced contradictory results, this issue is still subject to ongoing debate. We investigated the association of the eNOS E298D polymorphism with hypertension and with blood pressure (BP) in a large population-based sample of Caucasian ethnicity., Design: Cross-sectional study in a random sample of the general population., Methods: The eNOS E298D polymorphism was determined by 5'-exonuclease assay among 4219 participants aged 20-79 years of the Study of Health in Pomerania (SHIP)., Results: The percentages of the EE298, ED298 and DD298 genotypes were 49.2, 42.0 and 8.8%, respectively. The D allele frequencies did not differ between the groups of normotensive and hypertensive subjects (29.7 versus 29.9%, P = 0.812). Similarly, no association could be established between E298D genotype and prevalent hypertension, neither for D allele carriership (multivariate odds ratio 0.97, 95% confidence interval 0.83-1.12) nor for DD homozygosity (multivariate odds ratio 1.10, 95% confidence interval 0.84-1.43). Likewise, genotype groups did not differ as to the distribution of systolic (ANCOVA P = 0.917) or diastolic BP values (ANCOVA P = 0.657). Nearly identical results were obtained if the analyses were repeated sex-specifically or if subjects on antihypertensive medication were excluded., Conclusion: In a population-based cohort of Caucasians covering a broad age range, the eNOS E298D polymorphism is neither associated with prevalent hypertension nor with systolic or diastolic BP. These results do not support the hypothesis that the E298D polymorphism contributes to the genetic susceptibility to hypertension.
Published: 2005
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17. Meta-analysis identifies common and rare variants influencing blood pressure and overlapping with metabolic trait loci

Author: Liu, Chunyu, Kraja, Aldi T, Smith, Jennifer A, Brody, Jennifer A, Franceschini, Nora, Bis, Joshua C, Rice, Kenneth, Morrison, Alanna C, Lu, Yingchang, Weiss, Stefan, Guo, Xiuqing, Palmas, Walter, Martin, Lisa W, Chen, Yii-Der Ida, Surendran, Praveen, Drenos, Fotios, Cook, James P, Auer, Paul L, Chu, Audrey Y, Giri, Ayush, Zhao, Wei, Jakobsdottir, Johanna, Lin, Li-An, Stafford, Jeanette M, Amin, Najaf, Mei, Hao, Yao, Jie, Voorman, Arend, Larson, Martin G, Grove, Megan L, Smith, Albert V, Hwang, Shih-Jen, Chen, Han, Huan, Tianxiao, Kosova, Gulum, Stitziel, Nathan O, Kathiresan, Sekar, Samani, Nilesh, Schunkert, Heribert, Deloukas, Panos, Li, Man, Fuchsberger, Christian, Pattaro, Cristian, Gorski, Mathias, Kooperberg, Charles, Papanicolaou, George J, Rossouw, Jacques E, Faul, Jessica D, Kardia, Sharon LR, Bouchard, Claude, Raffel, Leslie J, Uitterlinden, André G, Franco, Oscar H, Vasan, Ramachandran S, O'Donnell, Christopher J, Taylor, Kent D, Liu, Kiang, Bottinger, Erwin P, Gottesman, Omri, Daw, E Warwick, Giulianini, Franco, Ganesh, Santhi, Salfati, Elias, Harris, Tamara B, Launer, Lenore J, Dörr, Marcus, Felix, Stephan B, Rettig, Rainer, Völzke, Henry, Kim, Eric, Lee, Wen-Jane, Lee, I-Te, Sheu, Wayne H-H, Tsosie, Krystal S, Edwards, Digna R Velez, Liu, Yongmei, Correa, Adolfo, Weir, David R, Völker, Uwe, Ridker, Paul M, Boerwinkle, Eric, Gudnason, Vilmundur, Reiner, Alexander P, van Duijn, Cornelia M, Borecki, Ingrid B, Edwards, Todd L, Chakravarti, Aravinda, Rotter, Jerome I, Psaty, Bruce M, Loos, Ruth JF, Fornage, Myriam, Ehret, Georg B, Newton-Cheh, Christopher, Levy, Daniel, and Chasman, Daniel I
Subjects: Biological Sciences, Genetics, Cardiovascular, Hypertension, Prevention, Biotechnology, 2.1 Biological and endogenous factors, Aetiology, Blood Pressure, Exome, Genetic Variation, Genome, Human, Genome-Wide Association Study, Genotype, Humans, Oligonucleotide Array Sequence Analysis, Polymorphism, Single Nucleotide, CHD Exome+ Consortium, ExomeBP Consortium, GoT2DGenes Consortium, T2D-GENES Consortium, Myocardial Infarction Genetics and CARDIoGRAM Exome Consortia, CKDGen Consortium, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract: Meta-analyses of association results for blood pressure using exome-centric single-variant and gene-based tests identified 31 new loci in a discovery stage among 146,562 individuals, with follow-up and meta-analysis in 180,726 additional individuals (total n = 327,288). These blood pressure-associated loci are enriched for known variants for cardiometabolic traits. Associations were also observed for the aggregation of rare and low-frequency missense variants in three genes, NPR1, DBH, and PTPMT1. In addition, blood pressure associations at 39 previously reported loci were confirmed. The identified variants implicate biological pathways related to cardiometabolic traits, vascular function, and development. Several new variants are inferred to have roles in transcription or as hubs in protein-protein interaction networks. Genetic risk scores constructed from the identified variants were strongly associated with coronary disease and myocardial infarction. This large collection of blood pressure-associated loci suggests new therapeutic strategies for hypertension, emphasizing a link with cardiometabolic risk.
Published: 2016

18. The Association of Serum Testosterone Levels and Ventricular Repolarization

Author: van Noord, Charlotte, Dörr, Marcus, Sturkenboom, Miriam C. J. M., Straus, Sabine M. J. M., Reffelmann, Thorsten, Felix, Stephan B., Hofman, Albert, Kors, Jan A., Haring, Robin, de Jong, Frank H., Nauck, Matthias, Uitterlinden, André G., Wallaschofski, Henri, Witteman, Jacqueline C. M., Völzke, Henry, and Stricker, Bruno H. Ch.
Published: 2010
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19. Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure

Author: Shah, Sonia, Henry, Albert, Roselli, Carolina, Lin, Honghuang, Sveinbjornsson, Gardar, Fatemifar, Ghazaleh, Hedman, Asa K, Wilk, Jemma B, Morley, Michael P, Chaffin, Mark D, Helgadottir, Anna, Verweij, Niek, Dehghan, Abbas, Almgren, Peter, Andersson, Charlotte, Aragam, Krishna G, Arnlov, Johan, Backman, Joshua D, Biggs, Mary L, Bloom, Heather L, Brandimarto, Jeffrey, Brown, Michael R, Buckbinder, Leonard, Carey, David J, Chasman, Daniel I, Chen, Xing, Chen, Xu, Chung, Jonathan, Chutkow, William, Cook, James P, Delgado, Graciela E, Denaxas, Spiros, Doney, Alexander S, Doerr, Marcus, Dudley, Samuel C, Dunn, Michael E, Engstrom, Gunnar, Esko, Tonu, Felix, Stephan B, Finan, Chris, Ford, Ian, Ghanbari, Mohsen, Ghasemi, Sahar, Giedraitis, Vilmantas, Giulianini, Franco, Gottdiener, John S, Gross, Stefan, Gudbjartsson, Daniel F, Gutmann, Rebecca, Haggerty, Christopher M, van der Harst, Pim, Hyde, Craig L, Ingelsson, Erik, Jukema, J Wouter, Kavousi, Maryam, Khaw, Kay-Tee, Kleber, Marcus E, Kober, Lars, Koekemoer, Andrea, Langenberg, Claudia, Lind, Lars, Lindgren, Cecilia M, London, Barry, Lotta, Luca A, Lovering, Ruth C, Luan, Jian'an, Magnusson, Patrik, Mahajan, Anubha, Margulies, Kenneth B, Maerz, Winfried, Melander, Olle, Mordi, Ify R, Morgan, Thomas, Morris, Andrew D, Morris, Andrew P, Morrison, Alanna C, Nagle, Michael W, Nelson, Christopher P, Niessner, Alexander, Niiranen, Teemu, O'Donoghue, Michelle L, Owens, Anjali T, Palmer, Colin NA, Parry, Helen M, Perola, Markus, Portilla-Fernandez, Eliana, Psaty, Bruce M, Rice, Kenneth M, Ridker, Paul M, Romaine, Simon PR, Rotter, Jerome I, Salo, Perttu, Salomaa, Veikko, van Setten, Jessica, Shalaby, Alaa A, Smelser, Diane T, Smith, Nicholas L, Stender, Steen, Stott, David J, Svensson, Per, Tammesoo, Mari-Liis, Taylor, Kent D, Teder-Laving, Maris, Teumer, Alexander, Thorgeirsson, Gudmundur, Thorsteinsdottir, Unnur, Torp-Pedersen, Christian, Trompet, Stella, Tyl, Benoit, Uitterlinden, Andre G, Veluchamy, Abirami, Voelker, Uwe, Voors, Adriaan A, Wang, Xiaosong, Wareham, Nicholas J, Waterworth, Dawn, Weeke, Peter E, Weiss, Raul, Wiggins, Kerri L, Xing, Heming, Yerges-Armstrong, Laura M, Yu, Bing, Zannad, Faiez, Zhao, Jing Hua, Hemingway, Harry, Samani, Nilesh J, McMurray, John JV, Yang, Jian, Visscher, Peter M, Newton-Cheh, Christopher, Malarstig, Anders, Holm, Hilma, Lubitz, Steven A, Sattar, Naveed, Holmes, Michael V, Cappola, Thomas P, Asselbergs, Folkert W, Hingorani, Aroon D, Kuchenbaecker, Karoline, Ellinor, Patrick T, Lang, Chim C, Stefansson, Kari, Smith, J Gustav, Vasan, Ramachandran S, Swerdlow, Daniel I, Lumbers, R Thomas, Abecasis, Goncalo, Backman, Joshua, Bai, Xiaodong, Balasubramanian, Suganthi, Banerjee, Nilanjana, Baras, Aris, Barnard, Leland, Beechert, Christina, Blumenfeld, Andrew, Cantor, Michael, Chai, Yating, Coppola, Giovanni, Damask, Amy, Dewey, Frederick, Economides, Aris, Eom, Gisu, Forsythe, Caitlin, Fuller, Erin D, Gu, Zhenhua, Gurski, Lauren, Guzzardo, Paloma M, Habegger, Lukas, Hahn, Young, Hawes, Alicia, van Hout, Cristopher, Jones, Marcus B, Khalid, Shareef, Lattari, Michael, Li, Alexander, Lin, Nan, Liu, Daren, Lopez, Alexander, Manoochehri, Kia, Marchini, Jonathan, Marcketta, Anthony, Maxwell, Evan K, McCarthy, Shane, Mitnaul, Lyndon J, O'Dushlaine, Colm, Overton, John D, Padilla, Maria Sotiropoulos, Paulding, Charles, Penn, John, Pradhan, Manasi, Reid, Jeffrey G, Schleicher, Thomas D, Schurmann, Claudia, Shuldiner, Alan, Staples, Jeffrey C, Sun, Dylan, Toledo, Karina, Ulloa, Ricardo H, Widom, Louis, Wolf, Sarah E, Yadav, Ashish, Ye, Bin, Ctr, Regeneron Genetics, Shah, Sonia [0000-0001-5860-4526], Henry, Albert [0000-0001-7422-2288], Roselli, Carolina [0000-0001-5267-6756], Lin, Honghuang [0000-0003-3043-3942], Chaffin, Mark D. [0000-0002-1234-5562], Helgadottir, Anna [0000-0002-1806-2467], Verweij, Niek [0000-0002-4303-7685], Almgren, Peter [0000-0002-0473-0241], Chen, Xu [0000-0002-7299-3238], Ghanbari, Mohsen [0000-0002-9476-7143], Giedraitis, Vilmantas [0000-0003-3423-2021], Gross, Stefan [0000-0003-4121-7161], Guðbjartsson, Daníel F. [0000-0002-5222-9857], Hyde, Craig L. [0000-0002-6939-287X], Ingelsson, Erik [0000-0003-2256-6972], Jukema, J. Wouter [0000-0002-3246-8359], Kleber, Marcus E. [0000-0003-0663-7275], Koekemoer, Andrea [0000-0001-8222-3547], Langenberg, Claudia [0000-0002-5017-7344], Lindgren, Cecilia M. [0000-0002-4903-9374], Lovering, Ruth C. [0000-0002-9791-0064], Luan, Jian’an [0000-0003-3137-6337], Magnusson, Patrik [0000-0002-7315-7899], Mahajan, Anubha [0000-0001-5585-3420], Mordi, Ify R. [0000-0002-2686-729X], Morris, Andrew D. [0000-0002-1766-0473], Nagle, Michael W. [0000-0002-4677-7582], Nelson, Christopher P. [0000-0001-8025-2897], Palmer, Colin N. A. [0000-0002-6415-6560], Rice, Kenneth M. [0000-0002-3071-7278], Rotter, Jerome I. [0000-0001-7191-1723], Salomaa, Veikko [0000-0001-7563-5324], van Setten, Jessica [0000-0002-4934-7510], Svensson, Per [0000-0003-0372-6272], Taylor, Kent D. [0000-0002-2756-4370], Teder-Laving, Maris [0000-0002-5872-1850], Teumer, Alexander [0000-0002-8309-094X], Tyl, Benoit [0000-0001-5297-8412], Uitterlinden, Andre G. [0000-0002-7276-3387], Völker, Uwe [0000-0002-5689-3448], Wiggins, Kerri L. [0000-0003-2749-1279], Hemingway, Harry [0000-0003-2279-0624], Yang, Jian [0000-0003-2001-2474], Visscher, Peter M. [0000-0002-2143-8760], Lubitz, Steven A. [0000-0002-9599-4866], Sattar, Naveed [0000-0002-1604-2593], Cappola, Thomas P. [0000-0002-9630-7204], Asselbergs, Folkert W. [0000-0002-1692-8669], Kuchenbaecker, Karoline [0000-0001-9726-603X], Ellinor, Patrick T. [0000-0002-2067-0533], Vasan, Ramachandran S. [0000-0001-7357-5970], Lumbers, R. Thomas [0000-0002-9077-4741], Apollo - University of Cambridge Repository, Chaffin, Mark D [0000-0002-1234-5562], Guðbjartsson, Daníel F [0000-0002-5222-9857], Hyde, Craig L [0000-0002-6939-287X], Jukema, J Wouter [0000-0002-3246-8359], Kleber, Marcus E [0000-0003-0663-7275], Lindgren, Cecilia M [0000-0002-4903-9374], Lovering, Ruth C [0000-0002-9791-0064], Luan, Jian'an [0000-0003-3137-6337], Mordi, Ify R [0000-0002-2686-729X], Morris, Andrew D [0000-0002-1766-0473], Nagle, Michael W [0000-0002-4677-7582], Nelson, Christopher P [0000-0001-8025-2897], Palmer, Colin NA [0000-0002-6415-6560], Rice, Kenneth M [0000-0002-3071-7278], Rotter, Jerome I [0000-0001-7191-1723], Taylor, Kent D [0000-0002-2756-4370], Uitterlinden, Andre G [0000-0002-7276-3387], Wiggins, Kerri L [0000-0003-2749-1279], Visscher, Peter M [0000-0002-2143-8760], Lubitz, Steven A [0000-0002-9599-4866], Cappola, Thomas P [0000-0002-9630-7204], Asselbergs, Folkert W [0000-0002-1692-8669], Ellinor, Patrick T [0000-0002-2067-0533], Vasan, Ramachandran S [0000-0001-7357-5970], Lumbers, R Thomas [0000-0002-9077-4741], Palmer, Colin N A [0000-0002-6415-6560], Cardiovascular Centre (CVC), University of Queensland [Brisbane], University College of London [London] (UCL), Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], University Medical Center Groningen [Groningen] (UMCG), Boston University School of Medicine (BUSM), Boston University [Boston] (BU), Framingham Heart Study, National Heart, Lung, and Blood Institute [Bethesda] (NHLBI)-Boston University [Boston] (BU), deCODE genetics [Reykjavik], Karolinska Institutet [Stockholm], Pfizer, University of Pennsylvania [Philadelphia], University of Groningen [Groningen], Imperial College London, Lund University [Lund], Herlev and Gentofte Hospital, Massachusetts General Hospital [Boston], Department of Neurobiology, Care Sciences and Society [Stockholm, Sweden] (Division of Family Medicine), Dalarna University, Regeneron Genetics Center, 777 Old Saw Mill River Road, Tarrytown, Department of Biostatistics, University of Washington [Seattle], Emory University School of Medicine, Emory University [Atlanta, GA], The University of Texas Medical School at Houston, Department of Molecular and Functional Genomics, Geisinger, Danville, PA, Brigham and Women's Hospital [Boston], Harvard Medical School [Boston] (HMS), Regeneron Genetics Center, 777 Old Saw Mill River Road, Tarrytown, NY, Novartis Institutes for BioMedical Research (NIBR), University of Liverpool, Universität Heidelberg [Heidelberg], Medizinische Fakultät Mannheim, The Alan Turing Institute, Ninewells Hospital and Medical School [Dundee], Universität Greifswald - University of Greifswald, German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), University of Minnesota System, Regeneron Pharmaceuticals [Tarrytown], Department of Clinical Sciences, Cardiovascular Epidemiology, Skane University Hospital [Lund], Institute of Genomics [Tartu, Estonia], University of Tartu, Robertson Centre for Biostatistics, University of Glasgow, Department of Epidemiology, Erasmus University Medical Center, Rotterdam, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Uppsala University, Brigham & Women’s Hospital [Boston] (BWH), University of Maryland School of Medicine, University of Maryland System, School of Science and Engineering (Reykjavik University), Carver College of Medicine, University of Iowa, Geisinger Health System [Danville, PA, USA], Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht, Stanford School of Medicine [Stanford], Stanford Medicine, Stanford University-Stanford University, Stanford Cardiovascular Institute, Uppsala Universitet [Uppsala], Leiden University Medical Center (LUMC), Einthoven Laboratory for Experimental Vascular Medicine (ELEVM - LEIDEN), Department of Public Health and Primary Care, University of Cambridge [UK] (CAM), Rigshospitalet [Copenhagen], Copenhagen University Hospital, Glenfield Hospital, University Hospitals Leicester, MRC Epidemiology Unit, University of Cambridge [UK] (CAM)-Institute of Metabolic Science, Big Data Institute, University of Oxford [Oxford], University of Iowa [Iowa City], The Wellcome Trust Centre for Human Genetics [Oxford], Synlab Academy, Synlab Holding Deutschland GmbH, Mannheim, Medical University Graz, Skane University Hospital [Malmo], Vanderbilt University School of Medicine [Nashville], University of Edinburgh, Université médicale de Vienne, Autriche, National Institute for Health and Welfare [Helsinki], University of Turku, Birmingham Women's and Children's NHS Foundation Trust, Kaiser Permanente, Harbor UCLA Medical Center [Torrance, Ca.], Los Angeles Biomedical Research Institute (LA BioMed), University Medical Center [Utrecht], University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE), Seattle Epidemiologic Research and Information Center [Seattle], Institute of Cardiovascular and Medical Sciences [Glasgow], University of Glasgow, Department of Cardiology, Södersjukhuset, Stockholm, Estonian Genome and Medicine, Landspitali National University Hospital of Iceland, University of Iceland [Reykjavik], Aalborg University [Denmark] (AAU), Institut de Recherches SERVIER (IRS), Interfaculty Institute for Genetics and Functional Genomics, Ernst-Moritz-Arndt-Universität Greifswald, GlaxoSmithKline, Glaxo Smith Kline, Northeastern Ohio Medical University (NEOMED), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, British Heart Foundation Glasgow Cardiovascular Research Centre (BHF GCRC), University of Glasgow-NHS Greater Glasgow and Clyde, Department of Cardiovascular Sciences [Leicester], University of Leicester, Queensland Brain Institute, Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, University of Dundee, National Heart and Lung Institute [London] (NHLI), Imperial College London-Royal Brompton and Harefield NHS Foundation Trust, Atherosclerosis Risk in Communities Study (ARIC)The Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts N01-HC-55015, N01-HC- 55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC55021, N01-HC-55022, R01HL087641, R01HL59367, R01HL086694 and RC2 HL102419, National Human Genome Research Institute contract U01HG004402, and National Institutes of Health contract HHSN268200625226C. The authors thank the staff and participants of the ARIC study for their important contributions. Infrastructure was partly supported by Grant Number UL1RR025005, a component of the National Institutes of Health and NIH Roadmap for Medical Research. A systems BIOlogy Study to TAilored Treatment in Chronic Heart Failure (BIOSTAT- CHF)This project was funded by a grant from the European Commission (FP7‐242209‐ BIOSTAT‐CHF, EudraCT 2010–020808–29). Cardiovascular Health Study (CHS) This CHS research was supported by NHLBI contracts HHSN268201200036C, HHSN268200800007C, HHSN268201800001C, HHSN268200960009C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, and NHLBI grants U01HL080295, R01HL087652, R01HL105756, R01HL103612, R01HL120393, and U01HL130114 with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided through R01AG023629 from the National Institute on Aging (NIA). A full list of principal CHS investigators and institutions can be found at CHS-NHLBI.org. The provision of genotyping data was supported in part by the National Center for Advancing Translational Sciences, CTSI grant UL1TR001881, and the National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center (DRC) grant DK063491 to the Southern California Diabetes Endocrinology Research Center. deCODE Heart Failure Study (deCODE) We at deCODE thank the women and men of Iceland that have participated in our studies and our colleagues that contributed to data collection and processing. DiscovEHR We acknowledge and thank all participants in Geisinger’s MyCode Community Health Initiative for their support and permission to use their health and genomic information in the DiscovEHR collaboration. This work was supported by the Regeneron Genetics Center and Geisinger. Estonian Genome Center at the University of Tartu (EGCUT) This study was supported by Estonian Research Council Grant IUT20-60, EU, H2020 grant 692145, European Union through the European Regional Development Fund (Project No. 2014-2020.4.01.15-0012) GENTRANSMED. Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) The EPHESUS was supported by Pfizer, Inc. The European Prospective Investigation of Cancer, Norfolk study (EPIC-Norfolk) The EPIC-Norfolk Study is supported by programme grants from the Medical Research Council UK (G1000143) and Cancer Research UK (C864/A14136) and with additional support from the European Union, Stroke Association, British Heart Foundation, Research into Ageing, Department of Health, The Wellcome Trust and the Food Standards Agency. NJW and CL also acknowledge support from the Medical Research Council, UK (MC_UU_12015/1, MC_PC_13048). We thank all EPIC participants and staff for their contribution to the study, and thank staff from the Technical, Field Epidemiology and Data Functional Group Teams of the Medical Research Council Epidemiology Unit in Cambridge, UK, for carrying out sample preparation, DNA provision and quality control, genotyping and data handling work. Framingham Heart Study (FHS) This work was conducted using data and resources from the Framingham Heart Study (FHS) of the National Heart Lung and Blood Institute and Boston University School of Medicine. The study was supported by the National Heart, Lung and Blood Institute’s Framingham Heart Study (Contract No. N01-HC-25195 and HHSN268201500001I) and its contract with Affymetrix, Inc for genotyping services (Contract No.N02-HL-6-4278). The work was also supported by R01 HL093328, R01 HL105993, and R01 HL71039 (PI: Ramachandran). FINRISK V.S. has been supported by the Finnish Foundation for Cardiovascular Research. Genetics of Diabetes Audit and Research Tayside Scotland GoDARTS) The Wellcome Trust United Kingdom Type 2 Diabetes Case Control Collection (supporting GoDARTS) was funded by the Wellcome Trust (072960/Z/03/Z, 084726/Z/08/Z, 084727/Z/08/Z, 085475/Z/08/Z, 085475/B/08/Z) and as part of the EU IMI-SUMMIT programme. We acknowledge the support of the Health Informatics Centre, University of Dundee, for managing and supplying the anonymized data and NHS Tayside, the original data owner. The Genetic Risk Assessment of Defibrillator Events (GRADE) NIH-NHLBI R01 HL77398 (Genetic Modulators of Sudden Death). S.L. is supported by NIH grant 1R01HL139731 and American Heart Association 18SFRN34250007. The LUdwigshafen RIsk and Cardiovascular Health (LURIC) study We extend our appreciation to the participants of the LURIC study, without their collaboration, this article would not have been written. We thank the LURIC study team who were either temporarily or permanently involved in patient recruitment as well as sample and data handling, in addition to the laboratory staff at the Ludwigshafen General Hospital and the Universities of Freiburg and Ulm, Germany. LURIC has received funding from the 7th Framework Program (RiskyCAD, grant agreement number 305739 and Atheroremo, grant agreement number 201668) of the European Union. Malmö Diet and Cancer Study (MDCS) J. Gustav Smith was supported by grants from the Swedish Heart-Lung Foundation (2016- 0134 and 2016-0315), the Swedish Research Council (2017-02554), the European Research Council (ERC-STG-2015-679242), the Crafoord Foundation, Skåne University Hospital, the Scania county, governmental funding of clinical research within the Swedish National Health Service, a generous donation from the Knut and Alice Wallenberg foundation to the Wallenberg Center for Molecular Medicine in Lund, and funding from the Swedish Research Council (Linnaeus grant Dnr 349-2006-237, Strategic Research Area Exodiab Dnr 2009-1039) and Swedish Foundation for Strategic Research (Dnr IRC15- 0067) to the Lund University Diabetes Center. The Malmo Diet and Cancer Study was made possible by grants from the Swedish Cancer Society, the Swedish Medical Research Council, the Swedish Dairy Association, and the Malmo city council. Penn Heart Failure Study (PHFS) The study was supported by NIH grants (NIH R01L088577 and NIH R01H105993). Prevention of REnal and Vascular ENd-stage Disease (PREVEND) The Prevention of Renal and Vascular Endstage Disease Study (PREVEND) genetics is supported by the Dutch Kidney Foundation (Grant E033), the EU project grant GENECURE (FP-6 LSHM CT 2006 037697), the National Institutes of Health (grant LM010098), the Netherlands organisation for health research and development (NWO VENI grant 916.761.70), and the Dutch Inter University Cardiology Institute Netherlands (ICIN). Niek Verweij was supported by NWO VENI grant 016.186.125. PROspective Study of Pravastatin in the Elderly at Risk for vascular disease (PROSPER)The PROSPER study was supported by an investigator-initiated grant obtained from Bristol- Myers Squibb. Support for genotyping was provided by the seventh framework program of the European commission (grant 223004) and by the Netherlands Genomics Initiative (Netherlands Consortium for Healthy Aging grant 050-060-810). J.W.J. is an Established Clinical Investigator of the Netherlands Heart Foundation (grant 2001 D 032). Study of Health in Pomerania (SHIP) SHIP is part of the Community Medicine Research net of the University of Greifswald, Germany, which is funded by the Federal Ministry of Education and Research (grants no. 01ZZ9603, 01ZZ0103, and 01ZZ0403), the Ministry of Cultural Affairs as well as the Social Ministry of the Federal State of Mecklenburg-West Pomerania, and the network ‘Greifswald Approach to Individualized Medicine (GANI_MED)’ funded by the Federal Ministry of Education and Research (grant 03IS2061A). Genome-wide data have been supported by the Federal Ministry of Education and Research (grant no. 03ZIK012) and a joint grant from Siemens Healthineers, Erlangen, Germany and the Federal State of Mecklenburg- West Pomerania. The University of Greifswald is a member of the Caché Campus program of the InterSystems GmbH. Stabilization of Plaque using Darapladib-Thrombolysis in Myocardial Infarction 52 (SOLID)SOLID-TIMI 52 was funded by GlaxoSmithKline. TwinGene (TwinGene) TwinGene received funding from the Swedish Research Council (M-2005-1112), GenomEUtwin (EU/QLRT-2001-01254, QLG2-CT-2002-01254), NIH DK U01-066134, The Swedish Foundation for Strategic Research (SSF) and the Heart and Lung foundation no. 20070481. TwinGene is part of the Swedish Twin Registry which is managed by Karolinska Institutet and receives funding through the Swedish Research Council (2017–00641). UK Biobank (UKBiobank) This research has been conducted using the UK Biobank Resource under Application Number 15422. This work was supported in part by grants to R.T.L. from the EU/EFPIA Innovative Medicines Initiative 2 Joint Undertaking BigData@Heart grant no. 116074, MRC Proximity to Discovery Award Scheme, the American Heart Association Institute for Precision Mecidine, Pfizer Ltd, the University College London British Heart Foundation Research Accelerator (AA/18/6/34223), and was supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. A. H. is supported by the British Heart Foundation Cardiovascular Biomedicine PhD studentship. R.T.L is supported by a UK Research and Innovation Rutherford Fellowship and was previously supported by a National Institutes of Health Research Clinical Lectureship. Uppsala Longitudinal Study of Adult Men (ULSAM) J.Ä. is supported by the Swedish Research Council and the Swedish Heart Lung foundation. C.M.L is supported by the Li Ka Shing Foundation, WT-SSI/John Fell funds and by the NIHR Biomedical Research Centre, Oxford, by Widenlife and NIH (5P50HD028138- 27). Women’s Genome Health Study (WGHS) The WGHS is supported by the National Heart, Lung, and Blood Institute (HL043851 and HL080467, HL099355) and the National Cancer Institute (CA047988 and UM1CA182913), with collaborative scientific support and funding for genotyping provided by Amgen., Epidemiology, Internal Medicine, Læknadeild (HÍ), Faculty of Medicine (UI), Verkfræði- og náttúruvísindasvið (HÍ), School of Engineering and Natural Sciences (UI), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Háskóli Íslands, and University of Iceland
Subjects: 0301 basic medicine, Dánartíðni, Epidemiology, LOCI, 45/43, General Physics and Astronomy, Muscle Proteins, Genome-wide association study, Disease, Coronary Artery Disease, 030204 cardiovascular system & hematology, Bioinformatics, Genome-wide association studies, DISEASE, Ventricular Function, Left, Coronary artery disease, 0302 clinical medicine, Risk Factors, Atrial Fibrillation, IMPUTATION, Medicine, Blóðrásarsjúkdómar, 692/308/174, lcsh:Science, 2. Zero hunger, RISK, Multidisciplinary, Microfilament Proteins, article, Atrial fibrillation, Mendelian Randomization Analysis, CATALOG, 3. Good health, OBESITY, Erfðarannsóknir, Cardiomyopathies, Medical Genetics, Cyclin-Dependent Kinase Inhibitor p21, Science, 631/208/205/2138, Heart failure, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 631/443/592/2727, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, RESOURCE, Humans, Mortality, METAANALYSIS, Genetic association, Medicinsk genetik, Adaptor Proteins, Signal Transducing, Heart Failure, HYPERTENSION, business.industry, Case-control study, Klinisk medicin, 692/699/75/230, General Chemistry, Cardiovascular genetics, medicine.disease, R1, 030104 developmental biology, Case-Control Studies, lcsh:Q, Morbidity, Clinical Medicine, business, Apoptosis Regulatory Proteins, Carrier Proteins, Genome-Wide Association Study
Abstract: Publisher's version (útgefin grein), Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies., We acknowledge the contribution from the EchoGen Consortium.
Published: 2020

20. Hypertension in Germany: Data From Seven Population-Based Epidemiological Studies (1994–2012)

Author: Neuhauser, Hannelore, Diederichs, Claudia, Boeing, Heiner, Felix, Stephan B., Jünger, Claus, Lorbeer, Roberto, Meisinger, Christine, Peters, Annette, Völzke, Henry, Weikert, Cornelia, Wild, Philipp, and Dörr, Marcus
Subjects: Adult, Male, Germany, Hypertension, Prevalence, Humans, Original Article, Blood Pressure, Female, Middle Aged, Health Surveys, Aged
Abstract: Hypertension is a key risk factor. However, population data based on blood pressure measurements in Germany are scarce.Standardized blood pressure (BP) measurements and medication data from seven population-based studies conducted in Germany between 1994 and 2012 (66 845 participants, 25-74 years) were analyzed: the EPICPotsdam study (1994-1998, EPIC), the KORA-S4 Study (1999-2001) in Augsburg, and the Gutenberg Health Study (2007-2012, GHS) in Mainz/Mainz-Bingen provided data for descriptive comparisons. Time trends were analyzed based on identical study regions for the German National Health Interview and Examination Survey 1998 (BGS98) and the German Health Examination Survey for Adults (2008-11, DEGS1) as well as the Study of Health in Pomerania (SHIP) in Northeast Germany (1997-2001) and the SHIP-TREND study (2008-2012). BP data were adjusted for study-specific measurement devices based on calibration studies.After adjustment for study-specific measurement devices, mean systolic and diastolic BP values were lower and treatment proportions higher in recent (2007-2012) compared to older (1994-2001) studies. Mean BP decrease was most pronounced (systolic ≥ 10 mmHg) in the elderly (55-74 years). The regional SHIP-TREND data for Northeast Germany showed a decrease in mean systolic BP in young men aged 25 to 34 years; on a national level according to the DEGS1 data, however, no such decrease was observed for this group.New data add evidence for lower BP in Germany. However, the prevention potential remains high. Future research based on population-based data should place a special focus on blood pressure data in young men.
Published: 2016

21. Subclinical hyperthyroidism and blood pressure in a populationbased prospective cohort study.

Author: Völzke, Henry, Ittermann, Till, Schmidt, Carsten O., Dörr, Marcus, John, Ulrich, Wallaschofski, Henri, Stricker, Bruno H. C., Felix, Stephan B., and Rettig, Rainer
Subjects: HYPERTHYROIDISM, BLOOD pressure, LONGITUDINAL method, COHORT analysis, HYPERTENSION, MEDICAL screening
Abstract: Objectives: There is current controversy on the association between subclinical hyperthyroidism and hypertension. Data from cohort studies have not been available yet. The present study was designed to longitudinally investigate possible associations of subclinical hyperthyroidism with blood pressure, pulse pressure and the risk of hypertension. Methods: We used data from the population-based, prospective cohort Study of Health in Pomerania and included 2910 subjects (1469 women) aged 20-79 years with completed 5-year examination follow-up. Subjects with increased serum TSH levels or overt hyperthyroidism were excluded. Serum TSH levels below 0.25 mIU/l with free triiodothyronine and free thyroxine levels within the reference range were defined as subclinical hyperthyroidism. Blood pressure was measured according to standard methods. Results: Multivariable analyses adjusted for age, sex, overweight, obesity, smoking status and time between the examinations did not reveal any statistically significant association between subclinical hyperthyroidism and any of the blood pressure-related variables in the whole study population. Although the 5-year hypertension incidence was higher in subjects with subclinical hyperthyroidism compared with those without (31.4 vs 19.2%; risk ratio 1.64; 95% confidence interval (CI) 1.17-2.28, P=0.006), both groups did not differ with respect to the risk of hypertension, after analyses were adjusted for confounders (relative risk 1.23, 95% CI 0.91-1.68, P=0.182). Analyses yielded similar results in subjects without thyroid disease and in those who took no antihypertensive medication. Conclusion: Subclinical hyperthyroidism is not associated with changes in blood pressure, pulse pressure or incident hypertension. [ABSTRACT FROM AUTHOR]
Published: 2009
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22. Prevalence and association analysis of obstructive sleep apnea with gender and age differences – Results of SHIP‐Trend.

Author: Fietze, Ingo, Laharnar, Naima, Obst, Anne, Ewert, Ralf, Felix, Stephan B., Garcia, Carmen, Gläser, Sven, Glos, Martin, Schmidt, Carsten Oliver, Stubbe, Beate, Völzke, Henry, Zimmermann, Sandra, and Penzel, Thomas
Subjects: SLEEP apnea syndromes, AGE differences, CARDIOVASCULAR diseases risk factors, DISEASE risk factors, WAIST-hip ratio, EPWORTH Sleepiness Scale
Abstract: Identification of obstructive sleep apnea and risk factors is important for reduction in symptoms and cardiovascular risk, and for improvement of quality of life. The population‐based Study of Health in Pomerania investigated risk factors and clinical diseases in a general population of northeast Germany. Additional polysomnography was applied to measure sleep and respiration with the objective of assessing prevalence and risk factors of obstructive sleep apnea in a German cohort. One‐thousand, two‐hundred and eight people between 20 and 81 years old (54% men, median age 54 years) underwent overnight polysomnography. The estimated obstructive sleep apnea prevalence was 46% (59% men, 33% women) for an apnea–hypopnea index ≥5%, and 21% (30% men, 13% women) for an apnea–hypopnea index ≥ 15. The estimated obstructive sleep apnea syndrome prevalence (apnea–hypopnea index ≥5; Epworth Sleepiness Scale >10) was 6%. The prevalence of obstructive sleep apnea continuously increased with age for men and women with, however, later onset for women. Gender, age, body mass index, waist‐to‐hip ratio, snoring, alcohol consumption (for women only) and self‐reported cardiovascular diseases were significantly positively associated with obstructive sleep apnea, whereas daytime sleepiness was not. Diabetes, hypertension and metabolic syndrome were positively associated with severe obstructive sleep apnea. The associations became non‐significant after adjustment for body mass. Women exhibited stronger associations than men. The prevalence of obstructive sleep apnea was high, with almost half the population presenting some kind of obstructive sleep apnea. The continuous increase of obstructive sleep apnea with age challenges the current theory that mortality due to obstructive sleep apnea and cardiovascular co‐morbidities affect obstructive sleep apnea prevalence at an advanced age. Also, gender differences regarding obstructive sleep apnea and associations are significant for recognizing obstructive sleep apnea mechanisms and therapy responsiveness. [ABSTRACT FROM AUTHOR]
Published: 2019
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23. Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals

Author: Surendran, Praveen, Feofanova, Elena V, Lahrouchi, Najim, Ntalla, Ioanna, Karthikeyan, Savita, Cook, James, Chen, Lingyan, Mifsud, Borbala, Yao, Chen, Kraja, Aldi T, Cartwright, James H, Hellwege, Jacklyn N, Giri, Ayush, Tragante, Vinicius, Thorleifsson, Gudmar, Liu, Dajiang J, Prins, Bram P, Stewart, Isobel D, Cabrera, Claudia P, Eales, James M, Akbarov, Artur, Auer, Paul L, Bielak, Lawrence F, Bis, Joshua C, Braithwaite, Vickie S, Brody, Jennifer A, Daw, E Warwick, Warren, Helen R, Drenos, Fotios, Nielsen, Sune Fallgaard, Faul, Jessica D, Fauman, Eric B, Fava, Cristiano, Ferreira, Teresa, Foley, Christopher N, Franceschini, Nora, Gao, He, Giannakopoulou, Olga, Giulianini, Franco, Gudbjartsson, Daniel F, Guo, Xiuqing, Harris, Sarah E, Havulinna, Aki S, Helgadottir, Anna, Huffman, Jennifer E, Hwang, Shih-Jen, Kanoni, Stavroula, Kontto, Jukka, Larson, Martin G, Li-Gao, Ruifang, Lindström, Jaana, Lotta, Luca A, Lu, Yingchang, Luan, Jian'an, Mahajan, Anubha, Malerba, Giovanni, Masca, Nicholas GD, Mei, Hao, Menni, Cristina, Mook-Kanamori, Dennis O, Mosen-Ansorena, David, Müller-Nurasyid, Martina, Paré, Guillaume, Paul, Dirk S, Perola, Markus, Poveda, Alaitz, Rauramaa, Rainer, Richard, Melissa, Richardson, Tom G, Sepúlveda, Nuno, Sim, Xueling, Smith, Albert V, Smith, Jennifer A, Staley, James R, Stanáková, Alena, Sulem, Patrick, Thériault, Sébastien, Thorsteinsdottir, Unnur, Trompet, Stella, Varga, Tibor V, Velez Edwards, Digna R, Veronesi, Giovanni, Weiss, Stefan, Willems, Sara M, Yao, Jie, Young, Robin, Yu, Bing, Zhang, Weihua, Zhao, Jing-Hua, Zhao, Wei, Evangelou, Evangelos, Aeschbacher, Stefanie, Asllanaj, Eralda, Blankenberg, Stefan, Bonnycastle, Lori L, Bork-Jensen, Jette, Brandslund, Ivan, Braund, Peter S, Burgess, Stephen, Cho, Kelly, Christensen, Cramer, Connell, John, Mutsert, Renée De, Dominiczak, Anna F, Dörr, Marcus, Eiriksdottir, Gudny, Farmaki, Aliki-Eleni, Gaziano, J Michael, Grarup, Niels, Grove, Megan L, Hallmans, Göran, Hansen, Torben, Have, Christian T, Heiss, Gerardo, Jørgensen, Marit E, Jousilahti, Pekka, Kajantie, Eero, Kamat, Mihir, Käräjämäki, AnneMari, Karpe, Fredrik, Koistinen, Heikki A, Kovesdy, Csaba P, Kuulasmaa, Kari, Laatikainen, Tiina, Lannfelt, Lars, Lee, I-Te, Lee, Wen-Jane, LifeLines Cohort Study, Linneberg, Allan, Martin, Lisa W, Moitry, Marie, Nadkarni, Girish, Neville, Matt J, Palmer, Colin NA, Papanicolaou, George J, Pedersen, Oluf, Peters, James, Poulter, Neil, Rasheed, Asif, Rasmussen, Katrine L, Rayner, N William, Mägi, Reedik, Renström, Frida, Rettig, Rainer, Rossouw, Jacques, Schreiner, Pamela J, Sever, Peter S, Sigurdsson, Emil L, Skaaby, Tea, Sun, Yan V, Sundstrom, Johan, Thorgeirsson, Gudmundur, Esko, Tõnu, Trabetti, Elisabetta, Tsao, Philip S, Tuomi, Tiinamaija, Turner, Stephen T, Tzoulaki, Ioanna, Vaartjes, Ilonca, Vergnaud, Anne-Claire, Willer, Cristen J, Wilson, Peter WF, Witte, Daniel R, Yonova-Doing, Ekaterina, Zhang, He, Aliya, Naheed, Almgren, Peter, Amouyel, Philippe, Asselbergs, Folkert W, Barnes, Michael R, Blakemore, Alexandra I, Boehnke, Michael, Bots, Michiel L, Bottinger, Erwin P, Buring, Julie E, Chambers, John C, Chen, Yii-Der Ida, Chowdhury, Rajiv, Conen, David, Correa, Adolfo, Davey Smith, George, Boer, Rudolf A De, Deary, Ian J, Dedoussis, George, Deloukas, Panos, Di Angelantonio, Emanuele, Elliott, Paul, EPIC-CVD, EPIC-InterAct, Felix, Stephan B, Ferrières, Jean, Ford, Ian, Fornage, Myriam, Franks, Paul W, Franks, Stephen, Frossard, Philippe, Gambaro, Giovanni, Gaunt, Tom R, Groop, Leif, Gudnason, Vilmundur, Harris, Tamara B, Hayward, Caroline, Hennig, Branwen J, Herzig, Karl-Heinz, Ingelsson, Erik, Tuomilehto, Jaakko, Järvelin, Marjo-Riitta, Jukema, J Wouter, Kardia, Sharon LR, Kee, Frank, Kooner, Jaspal S, Kooperberg, Charles, Launer, Lenore J, Lind, Lars, Loos, Ruth JF, Majumder, Abdulla Al Shafi, Laakso, Markku, McCarthy, Mark I, Melander, Olle, Mohlke, Karen L, Murray, Alison D, Nordestgaard, Børge Grønne, Orho-Melander, Marju, Packard, Chris J, Padmanabhan, Sandosh, Palmas, Walter, Polasek, Ozren, Porteous, David J, Prentice, Andrew M, Province, Michael A, Relton, Caroline L, Rice, Kenneth, Ridker, Paul M, Rolandsson, Olov, Rosendaal, Frits R, Rotter, Jerome I, Rudan, Igor, Salomaa, Veikko, Samani, Nilesh J, Sattar, Naveed, Sheu, Wayne H-H, Smith, Blair H, Soranzo, Nicole, Spector, Timothy D, Starr, John M, Sebert, Sylvain, Taylor, Kent D, Lakka, Timo A, Timpson, Nicholas J, Tobin, Martin D, Understanding Society Scientific Group, Van Der Harst, Pim, Van Der Meer, Peter, Ramachandran, Vasan S, Verweij, Niek, Virtamo, Jarmo, Völker, Uwe, Weir, David R, Zeggini, Eleftheria, Charchar, Fadi J, Million Veteran Program, Wareham, Nicholas J, Langenberg, Claudia, Tomaszewski, Maciej, Butterworth, Adam S, Caulfield, Mark J, Danesh, John, Edwards, Todd L, Holm, Hilma, Hung, Adriana M, Lindgren, Cecilia M, Liu, Chunyu, Manning, Alisa K, Morris, Andrew P, Morrison, Alanna C, O'Donnell, Christopher J, Psaty, Bruce M, Saleheen, Danish, Stefansson, Kari, Boerwinkle, Eric, Chasman, Daniel I, Levy, Daniel, Newton-Cheh, Christopher, Munroe, Patricia B, and Howson, Joanna MM
Subjects: Gene Frequency, Genotype, GATA5 Transcription Factor, Hypertension, Mutation, Phospholipase C beta, Humans, Blood Pressure, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, 3. Good health, Genome-Wide Association Study
Abstract: 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 × 10-8), 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.

24. A meta-analysis of gene expression signatures of blood pressure and hypertension

Author: Huan, Tianxiao, Esko, Tõnu, Peters, Marjolein J, Pilling, Luke C, Schramm, Katharina, Schurmann, Claudia, Chen, Brian H, Liu, Chunyu, Joehanes, Roby, Johnson, Andrew D, Yao, Chen, Ying, Sai-Xia, Courchesne, Paul, Milani, Lili, Raghavachari, Nalini, Wang, Richard, Liu, Poching, Reinmaa, Eva, Dehghan, Abbas, Hofman, Albert, Uitterlinden, André G, Hernandez, Dena G, Bandinelli, Stefania, Singleton, Andrew, Melzer, David, Metspalu, Andres, Carstensen, Maren, Grallert, Harald, Herder, Christian, Meitinger, Thomas, Peters, Annette, Roden, Michael, Waldenberger, Melanie, Dörr, Marcus, Felix, Stephan B, Zeller, Tanja, International Consortium For Blood Pressure GWAS (ICBP), Vasan, Ramachandran, O'Donnell, Christopher J, Munson, Peter J, Yang, Xia, Prokisch, Holger, Völker, Uwe, Van Meurs, Joyce BJ, Ferrucci, Luigi, and Levy, Daniel
Subjects: Gene Expression Regulation, Genotype, Hypertension, Humans, Blood Pressure, Genetic Predisposition to Disease, Transcriptome, Polymorphism, Single Nucleotide, 3. Good health, Genome-Wide Association Study
Abstract: Genome-wide association studies (GWAS) have uncovered numerous genetic variants (SNPs) that are associated with blood pressure (BP). Genetic variants may lead to BP changes by acting on intermediate molecular phenotypes such as coded protein sequence or gene expression, which in turn affect BP variability. Therefore, characterizing genes whose expression is associated with BP may reveal cellular processes involved in BP regulation and uncover how transcripts mediate genetic and environmental effects on BP variability. A meta-analysis of results from six studies of global gene expression profiles of BP and hypertension in whole blood was performed in 7017 individuals who were not receiving antihypertensive drug treatment. We identified 34 genes that were differentially expressed in relation to BP (Bonferroni-corrected p

25. Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries

Author: Feitosa, Mary F, Kraja, Aldi T, Chasman, Daniel I, Sung, Yun J, Winkler, Thomas W, Ntalla, Ioanna, Guo, Xiuqing, Franceschini, Nora, Cheng, Ching-Yu, Sim, Xueling, Vojinovic, Dina, Marten, Jonathan, Musani, Solomon K, Li, Changwei, Bentley, Amy R, Brown, Michael R, Schwander, Karen, Richard, Melissa A, Noordam, Raymond, Aschard, Hugues, Bartz, Traci M, Bielak, Lawrence F, Dorajoo, Rajkumar, Fisher, Virginia, Hartwig, Fernando P, Horimoto, Andrea RVR, Lohman, Kurt K, Manning, Alisa K, Rankinen, Tuomo, Smith, Albert V, Tajuddin, Salman M, Wojczynski, Mary K, Alver, Maris, Boissel, Mathilde, Cai, Qiuyin, Campbell, Archie, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Gao, Chuan, Goel, Anuj, Hagemeijer, Yanick, Harris, Sarah E, He, Meian, Hsu, Fang-Chi, Jackson, Anne U, Kähönen, Mika, Kasturiratne, Anuradhani, Komulainen, Pirjo, Kühnel, Brigitte, Laguzzi, Federica, Luan, Jian'an, Matoba, Nana, Nolte, Ilja M, Padmanabhan, Sandosh, Riaz, Muhammad, Rueedi, Rico, Robino, Antonietta, Said, M Abdullah, Scott, Robert A, Sofer, Tamar, Stančáková, Alena, Takeuchi, Fumihiko, Tayo, Bamidele O, Van Der Most, Peter J, Varga, Tibor V, Vitart, Veronique, Wang, Yajuan, Ware, Erin B, Warren, Helen R, Weiss, Stefan, Wen, Wanqing, Yanek, Lisa R, Zhang, Weihua, Zhao, Jing Hua, Afaq, Saima, Amin, Najaf, Amini, Marzyeh, Arking, Dan E, Aung, Tin, Boerwinkle, Eric, Borecki, Ingrid, Broeckel, Ulrich, Brown, Morris, Brumat, Marco, Burke, Gregory L, Canouil, Mickaël, Chakravarti, Aravinda, Charumathi, Sabanayagam, Ida Chen, Yii-Der, Connell, John M, Correa, Adolfo, De Las Fuentes, Lisa, De Mutsert, Renée, De Silva, H Janaka, Deng, Xuan, Ding, Jingzhong, Duan, Qing, Eaton, Charles B, Ehret, Georg, Eppinga, Ruben N, Evangelou, Evangelos, Faul, Jessica D, Felix, Stephan B, Forouhi, Nita G, Forrester, Terrence, Franco, Oscar H, Friedlander, Yechiel, Gandin, Ilaria, Gao, He, Ghanbari, Mohsen, Gigante, Bruna, Gu, C Charles, Gu, Dongfeng, Hagenaars, Saskia P, Hallmans, Göran, Harris, Tamara B, He, Jiang, Heikkinen, Sami, Heng, Chew-Kiat, Hirata, Makoto, Howard, Barbara V, Ikram, M Arfan, InterAct Consortium, John, Ulrich, Katsuya, Tomohiro, Khor, Chiea Chuen, Kilpeläinen, Tuomas O, Koh, Woon-Puay, Krieger, José E, Kritchevsky, Stephen B, Kubo, Michiaki, Kuusisto, Johanna, Lakka, Timo A, Langefeld, Carl D, Langenberg, Claudia, Launer, Lenore J, Lehne, Benjamin, Lewis, Cora E, Li, Yize, Lin, Shiow, Liu, Jianjun, Liu, Jingmin, Loh, Marie, Louie, Tin, Mägi, Reedik, McKenzie, Colin A, Meitinger, Thomas, Metspalu, Andres, Milaneschi, Yuri, Milani, Lili, Mohlke, Karen L, Momozawa, Yukihide, Nalls, Mike A, Nelson, Christopher P, Sotoodehnia, Nona, Norris, Jill M, O'Connell, Jeff R, Palmer, Nicholette D, Perls, Thomas, Pedersen, Nancy L, Peters, Annette, Peyser, Patricia A, Poulter, Neil, Raffel, Leslie J, Raitakari, Olli T, Roll, Kathryn, Rose, Lynda M, Rosendaal, Frits R, Rotter, Jerome I, Schmidt, Carsten O, Schreiner, Pamela J, Schupf, Nicole, Scott, William R, Sever, Peter S, Shi, Yuan, Sidney, Stephen, Sims, Mario, Sitlani, Colleen M, Smith, Jennifer A, Snieder, Harold, Starr, John M, Strauch, Konstantin, Stringham, Heather M, Tan, Nicholas YQ, Tang, Hua, Taylor, Kent D, Teo, Yik Ying, Tham, Yih Chung, Turner, Stephen T, Uitterlinden, André G, Vollenweider, Peter, Waldenberger, Melanie, Wang, Lihua, Wang, Ya Xing, Wei, Wen Bin, Williams, Christine, Yao, Jie, Yu, Caizheng, Yuan, Jian-Min, Zhao, Wei, Zonderman, Alan B, Becker, Diane M, Boehnke, Michael, Bowden, Donald W, Chambers, John C, Deary, Ian J, Esko, Tõnu, Farrall, Martin, Franks, Paul W, Freedman, Barry I, Froguel, Philippe, Gasparini, Paolo, Gieger, Christian, Jonas, Jost Bruno, Kamatani, Yoichiro, Kato, Norihiro, Kooner, Jaspal S, Kutalik, Zoltán, Laakso, Markku, Laurie, Cathy C, Leander, Karin, Lehtimäki, Terho, Study, Lifelines Cohort, Magnusson, Patrik KE, Oldehinkel, Albertine J, Penninx, Brenda WJH, Polasek, Ozren, Porteous, David J, Rauramaa, Rainer, Samani, Nilesh J, Scott, James, Shu, Xiao-Ou, Van Der Harst, Pim, Wagenknecht, Lynne E, Wareham, Nicholas J, Watkins, Hugh, Weir, David R, Wickremasinghe, Ananda R, Wu, Tangchun, Zheng, Wei, Bouchard, Claude, Christensen, Kaare, Evans, Michele K, Gudnason, Vilmundur, Horta, Bernardo L, Kardia, Sharon LR, Liu, Yongmei, Pereira, Alexandre C, Psaty, Bruce M, Ridker, Paul M, Van Dam, Rob M, Gauderman, W James, Zhu, Xiaofeng, Mook-Kanamori, Dennis O, Fornage, Myriam, Rotimi, Charles N, Cupples, L Adrienne, Kelly, Tanika N, Fox, Ervin R, Hayward, Caroline, Van Duijn, Cornelia M, Tai, E Shyong, Wong, Tien Yin, Kooperberg, Charles, Palmas, Walter, Rice, Kenneth, Morrison, Alanna C, Elliott, Paul, Caulfield, Mark J, Munroe, Patricia B, Rao, Dabeeru C, Province, Michael A, and Levy, Daniel
Subjects: Adult, Aged, 80 and over, Male, Adolescent, Alcohol Drinking, Racial Groups, Blood Pressure, Middle Aged, Polymorphism, Single Nucleotide, 3. Good health, Pedigree, Cohort Studies, Young Adult, Hypertension, Humans, Female, Gene-Environment Interaction, Genetic Predisposition to Disease, Aged, Genome-Wide Association Study
Abstract: Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in ≈131K individuals across several ancestry groups yielded 3,514 SNVs (245 loci) with suggestive evidence of association (P < 1.0 x 10-5). In Stage 2, these SNVs were tested for independent external replication in ≈440K individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2,159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 x 10-8). For African ancestry samples, we detected 18 potentially novel BP loci (P < 5.0 x 10-8) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2) have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension.

26. Riociguat for Patients With Pulmonary Hypertension Caused by Systolic Left Ventricular Dysfunction A Phase lib Double-Blind, Randomized, Placebo-Controlled, Dose-Ranging Hemodynamic Study.

Author: Bonderman, Diana, Ghio, Stefano, Felix, Stephan B., Ghofrani, Hossein-Ardeschir, Michelakis, Evangelos, Mitrovic, Veselin, Oudiz, Ronald J., Boateng, Francis, Scalise, Andrea-Viviana, Roessig, Lothar, and Semigran, Marc J.
Subjects: *PULMONARY hypertension, *HEART failure, *PLACEBOS, *HEMODYNAMICS, *GUANYLATE cyclase, *BLOOD pressure, *PATIENTS
Abstract: Background--Pulmonary hypertension caused by systolic left ventricular dysfunction is associated with significant morbidity and mortality; however, no treatment is approved for this indication. We hypothesized that riociguat, a novel soluble guanylate cyclase stimulator, would have beneficial hemodynamic effects in patients with pulmonary hypertension caused by systolic left ventricular dysfunction. Methods and Results--Overall, 201 patients with heart failure resulting from pulmonary hypertension caused by systolic left ventricular dysfunction were randomized to double-blind treatment with oral placebo or riociguat (0.5, 1, or 2 mg 3 times daily) for 16 weeks in 4 parallel arms. The primary outcome was the placebo-corrected change from baseline at week 16 in mean pulmonary artery pressure. Although the decrease in mean pulmonary artery pressure in the riociguat 2 mg group (-6.1±1.3 mmHg; P<0.0001 versus baseline) was not significantly different from placebo (P=0.10), cardiac index (0.4 L.min-1.m-2; 95% confidence interval, 0.2-0.5; P=0.0001) and stroke volume index (5.2 mL.m-2; 95% confidence interval, 2.0-8.4; P=0.0018) were significantly increased without changes in heart rate or systemic blood pressure compared with placebo. Both pulmonary (-46.6 dynes.s-1.cm-5; 95% confidence interval, -89.4 to -3.8; P=0.03) and systemic vascular resistance (-239.3 dynes.s-1.cm-5; 95% confidence interval, -363.4 to -115.3; P=0.0002) were significantly reduced with riociguat 2 mg. Riociguat reduced the Minnesota Living With Heart Failure score (P=0.0002). Discontinuation of treatment was similar between treatment groups. Conclusions--Although the primary end point of the study was not met, riociguat was well tolerated in patients with pulmonary hypertension caused by systolic left ventricular dysfunction and improved cardiac index and pulmonary and systemic vascular resistance. [ABSTRACT FROM AUTHOR]
Published: 2013
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27. Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-representative studies with 104 million participants

Author: Zhou, B, Carrillo-Larco, Rm, Danaei, G, Riley, Lm, Paciorek, Cj, Stevens, Ga, Gregg, Ew, Bennett, Je, Solomon, B, Singleton, Rk, Sophiea, Mk, Iurilli, Mlc, Lhoste, Vpf, Cowan, Mj, Savin, S, Woodward, M, Balanova, Y, Cifkova, R, Damasceno, A, Elliott, P, Farzadfar, F, He, J, Ikeda, N, Kengne, Ap, Khang, Yh, Kim, Hc, Laxmaiah, A, Lin, Hh, Maira, Pm, Miranda, Jj, Neuhauser, H, Sundstrom, J, Varghese, C, Widyahening, Is, Zdrojewski, T, Ezzati, M, Abarca-Gomez, L, Abdeen, Za, Rahim, Hfa, Abu-Rmeileh, Nm, Acosta-Cazares, B, Adams, Rj, Aekplakorn, W, Afsana, K, Afzal, S, Agdeppa, Ia, Aghazadeh-Attari, J, Aguilar-Salinas, Ca, Agyemang, C, Ahmad, Na, Ahmadi, A, Ahmadi, N, Ahmadizar, F, Ahmed, Sh, Ahrens, W, Ajlouni, K, Al-Raddadi, R, Alarouj, M, Albuhairan, F, Aldhukair, S, Ali, Mm, Alkandari, A, Alkerwi, A, Allin, K, Aly, E, Amarapurkar, Dn, Amougou, N, Amouyel, P, Andersen, Lb, Anderssen, Sa, Anjana, Rm, Ansari-Moghaddam, A, Ansong, D, Aounallah-Skhiri, H, Araujo, J, Ariansen, I, Aris, T, Arku, Re, Arlappa, N, Aryal, Kk, Aspelund, T, Assah, Fk, Assuncao, Mcf, Auvinen, J, Avdicova, M, Azevedo, A, Azimi-Nezhad, M, Azizi, F, Azmin, M, Babu, Bv, Bahijri, S, Balakrishna, N, Bamoshmoosh, M, Banach, M, Banadinovic, M, Bandosz, P, Banegas, Jr, Baran, J, Barbagallo, Cm, Barcelo, A, Barkat, A, Barreto, M, Barros, Ajd, Barros, Mvg, Bartosiewicz, A, Basit, A, Bastos, Jld, Bata, I, Batieha, Am, Batyrbek, A, Baur, La, Beaglehole, R, Belavendra, A, Ben Romdhane, H, Benet, M, Benson, Ls, Berkinbayev, S, Bernabe-Ortiz, A, Bettiol, H, Bezerra, J, Bhagyalaxmi, A, Bhargava, Sk, Bia, D, Biasch, K, Lele, Ecb, Bikbov, Mm, Bista, B, Bjerregaard, P, Bjertness, E, Bjertness, Mb, Bjorkelund, C, Bloch, Kv, Blokstra, A, Bo, S, Bobak, M, Boeing, H, Boggia, Jg, Boissonnet, Cp, Bojesen, Se, Bongard, V, Bonilla-Vargas, A, Bopp, M, Borghs, H, Bovet, P, Boyer, Cb, Braeckman, L, Brajkovich, I, Branca, F, Breckenkamp, J, Brenner, H, Brewster, Lm, Briceno, Y, Brito, M, Bruno, G, Bueno-de-Mesquita, Hb, Bueno, G, Bugge, A, Burns, C, Bursztyn, M, de Leon, Ac, Cacciottolo, J, Cameron, C, Can, G, Candido, Apc, Capanzana, Mv, Capkova, N, Capuano, E, Capuano, V, Cardoso, Vc, Carlsson, Ac, Carvalho, J, Casanueva, Ff, Censi, L, Cervantes-Loaiza, M, Chadjigeorgiou, Ca, Chamukuttan, S, Chan, Aw, Chan, Q, Chaturvedi, Hk, Chaturvedi, N, Chee, Ml, Chen, Cj, Chen, Ff, Chen, Hs, Chen, Sh, Chen, Zm, Cheng, Cy, Cheraghian, B, Dekkaki, Ic, Chetrit, A, Chien, Kl, Chiolero, A, Chiou, St, Chirita-Emandi, A, Chirlaque, Md, Cho, B, Christensen, K, Christofaro, Dg, Chudek, J, Cinteza, E, Claessens, F, Clarke, J, Clays, E, Cohen, E, Concin, H, Cooper, C, Coppinger, Tc, Costanzo, S, Cottel, D, Cowell, C, Craig, Cl, Crampin, Ac, Crujeiras, Ab, Cruz, Jj, Csilla, S, Cui, Lf, Cureau, Fv, Cuschieri, S, D'Arrigo, G, D'Orsi, E, Dallongeville, J, Dankner, R, Dantoft, Tm, Dauchet, L, Davletov, K, De Backer, G, De Bacquer, D, De Curtis, A, de Gaetano, G, De Henauw, S, de Oliveira, Pd, De Ridder, D, De Smedt, D, Deepa, M, Deev, Ad, Degennaro, V, Delisle, H, Demarest, S, Dennison, E, Deschamps, V, Dhimal, M, Di Castelnuovo, Af, Dias-da-Costa, Js, Diaz, A, Dickerson, Tt, Dika, Z, Djalalinia, S, Htp, Do, Dobson, Aj, Donfrancesco, C, Donoso, Sp, Doring, A, Dorobantu, M, Dorr, M, Doua, K, Dragano, N, Drygas, W, Duante, Ca, Duboz, P, Duda, Rb, Dulskiene, V, Dushpanova, A, Dzakula, A, Dzerve, V, Dziankowska-Zaborszczyk, E, Eddie, R, Eftekhar, E, Eggertsen, R, Eghtesad, S, Eiben, G, Ekelund, U, El-Khateeb, M, El Ati, J, Eldemire-Shearer, D, Eliasen, M, Elosua, R, Erasmus, Rt, Erbel, R, Erem, C, Eriksen, L, Eriksson, Jg, Escobedo-de la Pena, J, Eslami, S, Esmaeili, A, Evans, A, Faeh, D, Fakhretdinova, Aa, Fall, Ch, Faramarzi, E, Farjam, M, Fattahi, Mr, Fawwad, A, Felix-Redondo, Fj, Felix, Sb, Ferguson, Ts, Fernandes, Ra, Fernandez-Berges, D, Ferrante, D, Ferrao, T, Ferrari, M, Ferrario, Mm, Ferreccio, C, Ferreira, Hs, Ferrer, E, Ferrieres, J, Figueiro, Th, Fink, G, Fischer, K, Foo, Lh, Forsner, M, 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Montpellier (CIHEAM-IAMM), Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Interactions Gène-Environnement en Physiopathologie Cardio-Vasculaire (IGE-PCV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Clinicum, Research Programs Unit, Johan Eriksson / Principal Investigator, Department of General Practice and Primary Health Care, University of Helsinki, HUS Helsinki and Uusimaa Hospital District, Department of Public Health, 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Life, APH - Societal Participation & Health, Public and occupational health, APH - Health Behaviors & Chronic Diseases, VU University medical center, APH - Personalized Medicine, Psychiatry, APH - Mental Health, Bin Zhou, Rodrigo M Carrillo-Larco, Goodarz Danaei, Leanne M Riley, Christopher J Paciorek, Gretchen A Stevens, Edward W Gregg, James E Bennett, Bethlehem Solomon, Rosie K Singleton, Marisa K Sophiea, Maria Lc Iurilli, Victor Pf Lhoste, Melanie J Cowan, Stefan Savin, Mark Woodward, Yulia Balanova, Renata Cifkova, Albertino Damasceno, Paul Elliott, Farshad Farzadfar, Jiang He, Nayu Ikeda, Andre P Kengne, Young-Ho Khang, Hyeon Chang Kim, Avula Laxmaiah, Hsien-Ho Lin, Paula Margozzini Maira, J Jaime Miranda, Hannelore Neuhauser, Johan Sundström, Cherian Varghese, Indah S Widyahening, Tomasz Zdrojewski, Leandra Abarca-Gómez, Ziad A Abdeen, Hanan F Abdul Rahim, Niveen M Abu-Rmeileh, Benjamin Acosta-Cazares, Robert J Adams, Wichai Aekplakorn, Kaosar Afsana, Shoaib Afzal, Imelda A 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Huybrechts, Nahla Hwalla, Licia Iacoviello, Anna G Iannone, Mohsen M Ibrahim, Norazizah Ibrahim Wong, M Arfan Ikram, Violeta Iotova, Vilma E Irazola, Takafumi Ishida, Godsent C Isiguzo, Muhammad Islam, Sheikh Mohammed Shariful Islam, Masanori Iwasaki, Rod T Jackson, Jeremy M Jacobs, Hashem Y Jaddou, Tazeen Jafar, Kenneth James, Konrad Jamrozik, Imre Janszky, Edward Janus, Marjo-Riitta Jarvelin, Grazyna Jasienska, Ana Jelaković, Bojan Jelaković, Garry Jennings, Anjani Kumar Jha, Chao Qiang Jiang, Ramon O Jimenez, Karl-Heinz Jöckel, Michel Joffres, Mattias Johansson, Jari J Jokelainen, Jost B Jonas, Torben Jørgensen, Pradeep Joshi, Farahnaz Joukar, Jacek Jóżwiak, Anne Juolevi, Gregor Jurak, Vesna Jureša, Rudolf Kaaks, Anthony Kafatos, Eero O Kajantie, Zhanna Kalmatayeva, Natasa Kalpourtzi, Ofra Kalter-Leibovici, Freja B Kampmann, Srinivasan Kannan, Eva Karaglani, Line L Kårhus, Khem B Karki, Marzieh Katibeh, Joanne Katz, Jussi Kauhanen, Prabhdeep Kaur, Maryam Kavousi, Gyulli M Kazakbaeva, Ulrich Keil, Lital Keinan Boker, Sirkka Keinänen-Kiukaanniemi, Roya Kelishadi, Han Cg Kemper, Maryam Keramati, Alina Kerimkulova, Mathilde Kersting, Timothy Key, Yousef Saleh Khader, Davood Khalili, Kay-Tee Khaw, Bahareh Kheiri, Motahareh Kheradmand, Alireza Khosravi, Ursula Kiechl-Kohlendorfer, Stefan Kiechl, Japhet Killewo, Dong Wook Kim, Jeongseon Kim, Heidi Klakk, Magdalena Klimek, Jurate Klumbiene, Michael Knoflach, Elin Kolle, Patrick Kolsteren, Jukka P Kontto, Raija Korpelainen, Paul Korrovits, Jelena Kos, Seppo Koskinen, Katsuyasu Kouda, Sudhir Kowlessur, Slawomir Koziel, Jana Kratenova, Vilma Kriaucioniene, Peter Lund Kristensen, Steiner Krokstad, Daan Kromhout, Herculina S Kruger, Ruzena Kubinova, Renata Kuciene, Urho M Kujala, Zbigniew Kulaga, R Krishna Kumar, Pawel Kurjata, Yadlapalli S Kusuma, Vladimir Kutsenko, Kari Kuulasmaa, Catherine Kyobutungi, Tiina Laatikainen, Carl Lachat, Youcef Laid, Tai Hing Lam, Orlando Landrove, Vera Lanska, Georg Lappas, Bagher 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Dimitrios Papandreou, Soon-Woo Park, Suyeon Park, Winsome R Parnell, Mahboubeh Parsaeian, Patrick Pasquet, Nikhil D Patel, Halyna Pavlyshyn, Ivan Pećin, Mangesh S Pednekar, João M Pedro, Nasheeta Peer, Sergio Viana Peixoto, Markku Peltonen, Alexandre C Pereira, Karen Gda Peres, Marco A Peres, Annette Peters, Janina Petkeviciene, Niloofar Peykari, Son Thai Pham, Rafael N Pichardo, Iris Pigeot, Hynek Pikhart, Aida Pilav, Lorenza Pilotto, Freda Pitakaka, Aleksandra Piwonska, Andreia N Pizarro, Pedro Plans-Rubió, Ozren Polašek, Miquel Porta, Anil Poudyal, Farhad Pourfarzi, Akram Pourshams, Hossein Poustchi, Rajendra Pradeepa, Alison J Price, Jacqueline F Price, Rui Providencia, Soile E Puhakka, Maria Puiu, Margus Punab, Radwan F Qasrawi, Mostafa Qorbani, Daniel Queiroz, Tran Quoc Bao, Ivana Radić, Ricardas Radisauskas, Salar Rahimikazerooni, Mahfuzar Rahman, Olli Raitakari, Manu Raj, Ellina M Rakhimova, Sudha Ramachandra Rao, Ambady Ramachandran, Elisabete Ramos, Lekhraj Rampal, Sanjay Rampal, Daniel A Rangel Reina, Vayia Rarra, Cassiano Ricardo Rech, Josep Redon, Paul Ferdinand M Reganit, Valéria Regecová, Luis Revilla, Abbas Rezaianzadeh, Robespierre Ribeiro, Elio Riboli, Adrian Richter, Fernando Rigo, Tobias F Rinke de Wit, Raphael M Ritti-Dias, Cynthia Robitaille, Fernando Rodríguez-Artalejo, María Del Cristo Rodriguez-Perez, Laura A Rodríguez-Villamizar, Ulla Roggenbuck, Rosalba Rojas-Martinez, Dora Romaguera, Elisabetta L Romeo, Annika Rosengren, Joel Gr Roy, Adolfo Rubinstein, Jean-Bernard Ruidavets, Blanca Sandra Ruiz-Betancourt, Maria Ruiz-Castell, Iuliia A Rusakova, Paola Russo, Marcin Rutkowski, Charumathi Sabanayagam, Hamideh Sabbaghi, Harshpal S Sachdev, Alireza Sadjadi, Ali Reza Safarpour, Sare Safi, Saeid Safiri, Olfa Saidi, Sibel Sakarya, Nader Saki, Benoit Salanave, Eduardo Salazar Martinez, Diego Salmerón, Veikko Salomaa, Jukka T Salonen, Massimo Salvetti, Jose Sánchez-Abanto, Susana Sans, Diana A Santos, Ina S Santos, Lèlita C Santos, Maria Paula 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Krishna, Kurjata, Pawel, Kusuma, Yadlapalli S., Kutsenko, Vladimir, Kuulasmaa, Kari, Kyobutungi, Catherine, Laatikainen, Tiina, Lachat, Carl, Laid, Youcef, Lam, Tai Hing, Landrove, Orlando, Lanska, Vera, Lappas, Georg, Larijani, Bagher, Latt, Tint Swe, Le Coroller, Gwenaelle, Khanh Le Nguyen Bao, Le, Tuyen D., Lee, Jeannette, Lee, Jeonghee, Lehmann, Nils, Lehtimaki, Terho, Lemogoum, Daniel, Levitt, Naomi S., Li, Yanping, Lilly, Christa L., Lim, Wei-Yen, Lima-Costa, M. Fernanda, Lin, Xu, Lin, Yi-Ting, Lind, Lars, Lingam, Vijaya, Linneberg, Allan, Lissner, Lauren, Litwin, Mieczyslaw, Lo, Wei-Cheng, Loit, Helle-Mai, Lopez-Garcia, Esther, Lopez, Tania, Lotufo, Paulo A., Lozano, Jose Eugenio, Lovrencic, Iva Lukacevic, Lukrafka, Janice L., Luksiene, Dalia, Lundqvist, Annamari, Lundqvist, Robert, Lunet, Nuno, Lustigova, Michala, Luszczki, Edyta, Ma, Guansheng, Ma, Jun, Machado-Coelho, George L. L., Machado-Rodrigues, Aristides M., Macia, Enguerran, Macieira, Luisa M., Madar, Ahmed A., Maggi, Stefania, Magliano, Dianna J., Magriplis, Emmanuella, Mahasampath, Gowri, Maire, Bernard, Majer, Marjeta, Makdisse, Marcia, Malekzadeh, Fatemeh, Malekzadeh, Reza, Malhotra, Rahul, Mallikharjuna, Kodavanti, Malyutina, Sofia K., Maniego, Lynell V., Manios, Yannis, Mann, Jim I., Mansour-Ghanaei, Fariborz, Manzato, Enzo, Marcil, Anie, Margozzini, Paula, Marild, Staffan B., Glavic, Mihalea Marinovic, Marques-Vidal, Pedro, Marques, Larissa Pruner, Marrugat, Jaume, Martorell, Reynaldo, Mascarenhas, Luis P., Matasin, Marija, Mathiesen, Ellisiv B., Mathur, Prashant, Matijasevich, Alicia, Matlosz, Piotr, Matsha, Tandi E., Mavrogianni, Christina, Mbanya, Jean Claude N., Mc Donald Posso, Anselmo J., McFarlane, Shelly R., McGarvey, Stephen T., McLachlan, Stela, McLean, Rachael M., McLean, Scott B., McNulty, Breige A., Benchekor, Sounnia Mediene, Medzioniene, Jurate, Mehdipour, Parinaz, Mehlig, Kirsten, Mehrparvar, Amir Houshang, Meirhaeghe, Aline, Meisinger, Christa, Mendoza Montano, Carlos, Menezes, Ana Maria B., Menon, Geetha R., Mereke, Alibek, Meshram, Indrapal I., Metspalu, Andres, Meyer, Haakon E., Mi, Jie, Michels, Nathalie, Mikkel, Kairit, Milkowska, Karolina, Miller, Jody C., Minderico, Claudia S., Mini, G. K., Mirjalili, Mohammad Reza, Mirrakhimov, Erkin, Misigoj-Durakovic, Marjeta, Modesti, Pietro A., Moghaddam, Sahar Saeedi, Mohajer, Bahram, Mohamed, Mostafa K., Mohamed, Shukri F., Mohammad, Kazem, Mohammadi, Mohammad Reza, Mohammadi, Zahra, Mohammadifard, Noushin, Mohammadpourhodki, Reza, Mohan, Viswanathan, Mohanna, Salim, Yusoff, Muhammad Fadhli Mohd, Mohebbi, Iraj, Mohebi, Farnam, Moitry, Marie, Mollehave, Line T., Molnar, Denes, Momenan, Amirabbas, Mondo, Charles K., Monterrubio-Flores, Eric, Monyeki, Kotsedi Daniel K., Moon, Jin Soo, Moosazadeh, Mahmood, Moreira, Leila B., Morejon, Alain, Moreno, Luis A., Morgan, Karen, Moschonis, George, Mossakowska, Malgorzata, Mostafa, Aya, Mostafavi, Seyed-Ali, Mota, Jorge, Motlagh, Mohammad Esmaeel, Motta, Jorge, Andre Moura-dos-Santos, Marcos, Mridha, Malay K., Msyamboza, Kelias P., Mu, Thet Thet, Muhihi, Alfa J., Muiesan, Maria L., Muller-Nurasyid, Martina, Murphy, Neil, Mursu, Jaakko, Musa, Kamarul Imran, Milanovic, Sanja Music, Musil, Vera, Mustafa, Norlaila, Nabipour, Iraj, Naderimagham, Shohreh, Nagel, Gabriele, Naidu, Balkish M., Najafi, Farid, Nakamura, Harunobu, Namesna, Jana, Nang, Ei Ei K., Nangia, Vinay B., Narake, Sameer, Ndiaye, Ndeye Coumba, Neal, William A., Nejatizadeh, Azim, Nenko, Ilona, Neovius, Martin, Neuhauser, Hannelore K., Nguyen, Chung T., Nguyen, Nguyen D., Nguyen, Quang V., Quang Ngoc Nguyen, Nieto-Martinez, Ramfis E., Niiranen, Teemu J., Nikitin, Yury P., Ninomiya, Toshiharu, Nishtar, Sania, Njelekela, Marina A., Noale, Marianna, Noboa, Oscar A., Noorbala, Ahmad Ali, Norat, Teresa, Nordendahl, Maria, Nordestgaard, Borge G., Noto, Davide, Nowak-Szczepanska, Natalia, Al Nsour, Mohannad, Nunes, Baltazar, O'Neill, Terence W., O'Reilly, Dermot, Ochimana, Caleb, Oda, Eiji, Odili, Augustine N., Oh, Kyungwon, Ohara, Kumiko, Ohtsuka, Ryutaro, Olie, Valerie, Olinto, Maria Teresa A., Oliveira, Isabel O., Omar, Mohd Azahadi, Onat, Altan, Ong, Sok King, Ono, Lariane M., Ordunez, Pedro, Ornelas, Rui, Ortiz, Pedro J., Osmond, Clive, Ostojic, Sergej M., Ostovar, Afshin, Otero, Johanna A., Overvad, Kim, Owusu-Dabo, Ellis, Paccaud, Fred Michel, Padez, Cristina, Pahomova, Elena, de Paiva, Karina Mary, Pajak, Andrzej, Palli, Domenico, Palmieri, Luigi, Pan, Wen-Harn, Panda-Jonas, Songhomitra, Panza, Francesco, Paoli, Mariela, Papandreou, Dimitrios, Park, Soon-Woo, Park, Suyeon, Parnell, Winsome R., Parsaeian, Mahboubeh, Pasquet, Patrick, Patel, Nikhil D., Pavlyshyn, Halyna, Pecin, Ivan, Pednekar, Mangesh S., Pedro, Joao M., Peer, Nasheeta, Peixoto, Sergio Viana, Peltonen, Markku, Pereira, Alexandre C., Peres, Karen G. D. A., Peres, Marco A., Peters, Annette, Petkeviciene, Janina, Peykari, Niloofar, Son Thai Pham, Pichardo, Rafael N., Pigeot, Iris, Pikhart, Hynek, Pilav, Aida, Pilotto, Lorenza, Pitakaka, Freda, Piwonska, Aleksandra, Pizarro, Andreia N., Plans-Rubio, Pedro, Polasek, Ozren, Porta, Miquel, Poudyal, Anil, Pourfarzi, Farhad, Pourshams, Akram, Poustchi, Hossein, Pradeepa, Rajendra, Price, Alison J., Price, Jacqueline F., Providencia, Rui, Puhakka, Soile E., Puiu, Maria, Punab, Margus, Qasrawi, Radwan F., Qorbani, Mostafa, Queiroz, Daniel, Tran Quoc Bao, Radic, Ivana, Radisauskas, Ricardas, Rahimikazerooni, Salar, Rahman, Mahfuzar, Raitakari, Olli, Raj, Manu, Rakhimova, Ellina M., Rao, Sudha Ramachandra, Ramachandran, Ambady, Ramos, Elisabete, Rampal, Lekhraj, Rampal, Sanjay, Rangel Reina, Daniel A., Rarra, Vayia, Rech, Cassiano Ricardo, Redon, Josep, Reganit, Paul Ferdinand M., Regecova, Valeria, Revilla, Luis, Rezaianzadeh, Abbas, Ribeiro, Robespierre, Riboli, Elio, Richter, Adrian, Rigo, Fernando, de Wit, Tobias F. Rinke, Ritti-Dias, Raphael M., Robitaille, Cynthia, Rodriguez-Artalejo, Fernando, del Cristo Rodriguez-Perez, Maria, Rodriguez-Villamizar, Laura A., Roggenbuck, Ulla, Rojas-Martinez, Rosalba, Romaguera, Dora, Romeo, Elisabetta L., Rosengren, Annika, Roy, Joel G. R., Rubinstein, Adolfo, Ruidavets, Jean-Bernard, Sandra Ruiz-Betancourt, Blanca, Ruiz-Castell, Maria, Rusakova, Iuliia A., Russo, Paola, Rutkowski, Marcin, Sabanayagam, Charumathi, Sabbaghi, Hamideh, Sachdev, Harshpal S., Sadjadi, Alireza, Safarpour, Ali Reza, Safi, Sare, Safiri, Saeid, Saidi, Olfa, Saki, Nader, Salanave, Benoit, Salazar Martinez, Eduardo, Salmeron, Diego, Salomaa, Veikko, Salonen, Jukka T., Salvetti, Massimo, Sanchez-Abanto, Jose, Sans, Susana, Santos, Diana A., Santos, Ina S., Santos, Lelita C., Santos, Maria Paula, Santos, Rute, Saramies, Jouko L., Sardinha, Luis B., Sarganas, Giselle, Sarrafzadegan, Nizal, Sathish, Thirunavukkarasu, Saum, Kai-Uwe, Savva, Savvas, Sawada, Norie, Sbaraini, Mariana, Scazufca, Marcia, Schaan, Beatriz D., Schargrodsky, Herman, Schipf, Sabine, Schmidt, Carsten O., Schnohr, Peter, Schoettker, Ben, Schramm, Sara, Schultsz, Constance, Schutte, Aletta E., Sebert, Sylvain, Sein, Aye Aye, Sen, Abhijit, Senbanjo, Idowu O., Sepanlou, Sadaf G., Servais, Jennifer, Shalnova, Svetlana A., Shamah-Levy, Teresa, Shamshirgaran, Morteza, Shanthirani, Coimbatore Subramaniam, Sharafkhah, Maryam, Sharma, Sanjib K., Shaw, Jonathan E., Shayanrad, Amaneh, Shayesteh, Ali Akbar, Shi, Zumin, Shibuya, Kenji, Shimizu-Furusawa, Hana, Shin, Dong Wook, Shirani, Majid, Shiri, Rahman, Shrestha, Namuna, Si-Ramlee, Khairil, Siani, Alfonso, Siantar, Rosalynn, Sibai, Abla M., de Moura Silva, Caroline Ramos, Santos Silva, Diego Augusto, Simon, Mary, Simons, Judith, Simons, Leon A., Sjostrom, Michael, Slowikowska-Hilczer, Jolanta, Slusarczyk, Przemyslaw, Smeeth, Liam, So, Hung-Kwan, Soares, Fernanda Cunha, Sobngwi, Eugene, Soderberg, Stefan, Soemantri, Agustinus, Sofat, Reecha, Solfrizzi, Vincenzo, Somi, Mohammad Hossein, Sonestedt, Emily, Song, Yi, Sorensen, Thorkild I. A., Sorgjerd, Elin P., Soric, Maroje, Jerome, Charles Sossa, Soumare, Aicha, Sparboe-Nilsen, Bente, Sparrenberger, Karen, Staessen, Jan A., Starc, Gregor, Stavreski, Bill, Steene-Johannessen, Jostein, Stehle, Peter, Stein, Aryeh D., Stergiou, George S., Stessman, Jochanan, Stieber, Jutta, Stoeckl, Doris, Stocks, Tanja, Stokwiszewski, Jakub, Stronks, Karien, Strufaldi, Maria Wany, Suka, Machi, Sun, Chien-An, Sung, Yn-Tz, Suriyawongpaisal, Paibul, Sy, Rody G., Syddall, Holly E., Sylva, Rene Charles, Szklo, Moyses, Tai, E. Shyong, Tammesoo, Mari-Liis, Tamosiunas, Abdonas, Tan, Eng Joo, Tang, Xun, Tanser, Frank, Tao, Yong, Tarawneh, Mohammed Rasoul, Tarqui-Mamani, Carolina B., Taylor, Anne, Taylor, Julie, Tebar, William R., Tell, Grethe S., Tello, Tania, Tham, Yih Chung, Thankappan, K. R., Theobald, Holger, Theodoridis, Xenophon, Thinggaard, Mikael, Thomas, Nihal, Thorand, Barbara, Thuesen, Betina H., Timmermans, Erik J., Tjandrarini, Dwi H., Tjonneland, Anne, Toft, Ulla, Tolonen, Hanna K., Tolstrup, Janne S., Topbas, Murat, Topor-Madry, Roman, Jose Tormo, Maria, Tornaritis, Michael J., Torrent, Maties, Torres-Collado, Laura, Touloumi, Giota, Traissac, Pierre, Triantafyllou, Areti, Trichopoulos, Dimitrios, Trichopoulou, Antonia, Trinh, Oanh T. H., Trivedi, Atul, Tshepo, Lechaba, Tsugane, Shoichiro, Tuliakova, Azaliia M., Tulloch-Reid, Marshall K., Tullu, Fikru, Tuomainen, Tomi-Pekka, Tuomilehto, Jaakko, Turley, Maria L., Twig, Gilad, Tynelius, Per, Tzourio, Christophe, Ueda, Peter, Ugel, Eunice, Ulmer, Hanno, Uusitalo, Hannu M. T., Valdivia, Gonzalo, Valvi, Damaskini, van Dam, Rob M., van den Born, Bert-Jan, Van der Heyden, Johan, van der Schouw, Yvonne T., Van Herck, Koen, Hoang Van Minh, Van Schoor, Natasja M., van Valkengoed, Irene G. M., van Zutphen, Elisabeth M., Vanuzzo, Diego, Varbo, Anette, Vasan, Senthil K., Vega, Tomas, Veidebaum, Toomas, Velasquez-Melendez, Gustavo, Veronesi, Giovanni, Verschuren, W. M. Monique, Verstraeten, Roosmarijn, Victora, Cesar G., Viet, Lucie, Villalpando, Salvador, Vineis, Paolo, Vioque, Jesus, Virtanen, Jyrki K., Visvikis-Siest, Sophie, Viswanathan, Bharathi, Vlasoff, Tiina, Vollenweider, Peter, Voutilainen, Ari, Wade, Alisha N., Walton, Janette, Wambiya, Elvis O. A., Bebakar, Wan Mohamad Wan, Mohamud, Wan Nazaimoon Wan, Wanderley Junior, Rildo de Souza, Wang, Ming-Dong, Wang, Ningli, Wang, Qian, Wang, Xiangjun, Wang, Ya Xing, Wang, Ying-Wei, Wannamethee, S. Goya, Wareham, Nicholas, Wei, Wenbin, Weres, Aneta, Werner, Bo, Whincup, Peter H., Widhalm, Kurt, Wiecek, Andrzej, Wilks, Rainford J., Willeit, Johann, Willeit, Peter, Williams, Emmanuel A., Wilsgaard, Tom, Wojtyniak, Bogdan, Wong-McClure, Roy A., Wong, Andrew, Wong, Tien Yin, Woo, Jean, Wu, Frederick C., Wu, Shouling, Wyszynska, Justyna, Xu, Haiquan, Xu, Liang, Yaacob, Nor Azwany, Yan, Weili, Yang, Ling, Yang, Xiaoguang, Yang, Yang, Yasuharu, Tabara, Ye, Xingwang, Yiallouros, Panayiotis K., Yoosefi, Moein, Yoshihara, Akihiro, You, San-Lin, Younger-Coleman, Novie O., Yusoff, Ahmad Faudzi, Zainuddin, Ahmad A., Zakavi, Seyed Rasoul, Zamani, Farhad, Zambon, Sabina, Zampelas, Antonis, Elisa Zapata, Maria, Zaw, Ko Ko, Zejglicova, Kristyna, Vrkic, Tajana Zeljkovic, Zeng, Yi, Zhang, Luxia, Zhao, Dong, Zhao, Ming-Hui, Zhen, Shiqi, Zheng, Yingfeng, Zholdin, Bekbolat, Zhu, Dan, Zins, Marie, Zitt, Emanuel, Zocalo, Yanina, Zoghlami, Nada, Zuniga Cisneros, Julio., School of Medicine, ACS - Diabetes & metabolism, APH - Global Health, Pulmonology, Medical Informatics, Adult Psychiatry, Global Health, APH - Quality of Care, APH - Methodology, Vascular Medicine, ACS - Atherosclerosis & ischemic syndromes, Anesthesiology, Graduate School, and ACS - Heart failure & arrhythmias
Subjects: Male, Latin Americans, Nutrition and Disease, Epidemiology, [SDV]Life Sciences [q-bio], Medizin, BLOOD-PRESSURE, 030204 cardiovascular system & hematology, Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-representative studies with 104 million participants, Hypertension, Prevalence, Control, Tretament, GUIDELINES, Global Health, Worldwide trends, 0302 clinical medicine, Hypertension prevalence, Voeding en Ziekte, Medicine and Health Sciences, kohonnut verenpaine, Medicine, 030212 general & internal medicine, Prevention and Control, 11 Medical and Health Sciences, ComputingMilieux_MISCELLANEOUS, education.field_of_study, food and beverages, Public Health, Global Health, Social Medicine and Epidemiology, General Medicine, Noncommunicable diseases, Period prevalence, Middle Aged, kansainvälinen vertailu, 3142 Public health care science, environmental and occupational health, 3. Good health, MIDDLE-INCOME, Pooled analysis, SYSTEMATIC ANALYSIS, INCOME COUNTRIES, ADULTS, PREVENTION, MANAGEMENT, ADHERENCE, DIAGNOSIS, Western europe, [SDE]Environmental Sciences, Hypertension/diagnosis, NCD Risk Factor Collaboration (NCD-RisC), Female, B990 Subjects Allied to Medicine not elsewhere classified, Life Sciences & Biomedicine, Adult, health-care, esiintyvyys, Central asia, Population, Nursing, 3121 Internal medicine, 03 medical and health sciences, Medicine, General & Internal, Drug Therapy, General & Internal Medicine, Life Science, Humans, ddc:610, education, Antihypertensive Agents, VLAG, Aged, Science & Technology, Antihypertensive Agents/therapeutic use, business.industry, Omvårdnad, fungi, General and internal medicine, Estados de Saúde e de Doença, Taking medication, Treatment, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Blood pressure, Faculdade de Ciências Sociais, 3121 General medicine, internal medicine and other clinical medicine, lääkehoito, 1182 Biochemistry, cell and molecular biology, business, Demography
Abstract: Background: hypertension can be detected at the primary health-care level and low-cost treatments can effectively control hypertension. We aimed to measure the prevalence of hypertension and progress in its detection, treatment, and control from 1990 to 2019 for 200 countries and territories. Methods: we used data from 1990 to 2019 on people aged 30-79 years from population-representative studies with measurement of blood pressure and data on blood pressure treatment. We defined hypertension as having systolic blood pressure 140 mm Hg or greater, diastolic blood pressure 90 mm Hg or greater, or taking medication for hypertension. We applied a Bayesian hierarchical model to estimate the prevalence of hypertension and the proportion of people with hypertension who had a previous diagnosis (detection), who were taking medication for hypertension (treatment), and whose hypertension was controlled to below 140/90 mm Hg (control). The model allowed for trends over time to be non-linear and to vary by age. Findings: the number of people aged 30-79 years with hypertension doubled from 1990 to 2019, from 331 (95% credible interval 306-359) million women and 317 (292-344) million men in 1990 to 626 (584-668) million women and 652 (604-698) million men in 2019, despite stable global age-standardised prevalence. In 2019, age-standardised hypertension prevalence was lowest in Canada and Peru for both men and women; in Taiwan, South Korea, Japan, and some countries in western Europe including Switzerland, Spain, and the UK for women; and in several low-income and middle-income countries such as Eritrea, Bangladesh, Ethiopia, and Solomon Islands for men. Hypertension prevalence surpassed 50% for women in two countries and men in nine countries, in central and eastern Europe, central Asia, Oceania, and Latin America. Globally, 59% (55-62) of women and 49% (46-52) of men with hypertension reported a previous diagnosis of hypertension in 2019, and 47% (43-51) of women and 38% (35-41) of men were treated. Control rates among people with hypertension in 2019 were 23% (20-27) for women and 18% (16-21) for men. In 2019, treatment and control rates were highest in South Korea, Canada, and Iceland (treatment >70%; control >50%), followed by the USA, Costa Rica, Germany, Portugal, and Taiwan. Treatment rates were less than 25% for women and less than 20% for men in Nepal, Indonesia, and some countries in sub-Saharan Africa and Oceania. Control rates were below 10% for women and men in these countries and for men in some countries in north Africa, central and south Asia, and eastern Europe. Treatment and control rates have improved in most countries since 1990, but we found little change in most countries in sub-Saharan Africa and Oceania. Improvements were largest in high-income countries, central Europe, and some upper-middle-income and recently high-income countries including Costa Rica, Taiwan, Kazakhstan, South Africa, Brazil, Chile, Turkey, and Iran. Interpretation Improvements in the detection, treatment, and control of hypertension have varied substantially across countries, with some middle-income countries now outperforming most high-income nations. The dual approach of reducing hypertension prevalence through primary prevention and enhancing its treatment and control is achievable not only in high-income countries but also in low-income and middle-income settings., British Heart Foundation Centre of Research Excellence Grant; World Health Organization (WHO); Abdul Latif Jameel Institute for Disease and Emergency Analytics Fellowship
Published: 2021

28. Low serum magnesium concentrations predict cardiovascular and all-cause mortality

Author: Reffelmann, Thorsten, Ittermann, Till, Dörr, Marcus, Völzke, Henry, Reinthaler, Markus, Petersmann, Astrid, and Felix, Stephan B.
Subjects: *SERUM, *MAGNESIUM, *HYPERTROPHY, *LEFT heart ventricle, *CARDIOVASCULAR diseases risk factors, *ANTIHYPERTENSIVE agents, *FOLLOW-up studies (Medicine), CARDIOVASCULAR disease related mortality
Abstract: Abstract: Background: Low serum magnesium (Mg++) levels are associated with future development of left ventricular hypertrophy independently of common cardiovascular risk factors, as recently demonstrated in the five-year follow-up of the population-based Study of Health in Pomerania (SHIP). As left ventricular hypertrophy has significant prognostic implications, we hypothesized that serum Mg++ levels are associated with cardiovascular mortality. Method and results: All-cause mortality and cardiovascular mortality were analyzed in relationship to serum Mg++ concentrations at baseline by Cox proportional hazard model in SHIP (n =4203, exclusion of subjects with Mg++ supplementation). The median duration of mortality follow-up was 10.1 years (25th percentile: 9.4 years, 75th percentile: 10.8 years; 38,075person-years). During the follow-up, 417 deaths occurred. Mortality in subjects with Mg++ ≤0.73mmol/l was significantly higher for all-cause deaths (10.95 death per 1000 person years), and cardiovascular deaths (3.44 deaths per 1000 person years) in comparison to higher Mg++ concentrations (1.45 deaths from all-cause per 1000 person years, 1.53 deaths from cardiovascular cause per 1000 person years). This association remained statistically significant after adjustment for multiple cardiovascular risk factors, including arterial hypertension, and antihypertensive therapy including diuretics (log-rank-test p =0.0001 for all-cause mortality, and p =0.0174 for cardiovascular mortality). Conclusions: Low serum Mg++ levels are associated with higher all-cause mortality and cardiovascular mortality. This corresponds well with recent findings that hypomagnesemia is associated with the increase of left ventricular mass over the following years. [Copyright &y& Elsevier]
Published: 2011
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29. Association between glycosylated haemoglobin A1c and endothelial function in an adult non-diabetic population

Author: Lorbeer, Roberto, Empen, Klaus, Dörr, Marcus, Arndt, Maria, Schipf, Sabine, Nauck, Matthias, Wallaschofski, Henri, Felix, Stephan B., and Völzke, Henry
Subjects: *GLYCOSYLATED hemoglobin, *VASCULAR endothelium, *PEOPLE with diabetes, *ATHEROSCLEROSIS, *CARDIOVASCULAR diseases risk factors, *BRACHIAL artery, *HYPERTENSION, *LABORATORY dogs
Abstract: Abstract: Objective: Endothelial dysfunction precedes apparent atherosclerosis in humans and is associated with a number of cardiovascular risk factors, including Type 2 diabetes. To investigate the impact of long-term glucose homeostasis on endothelial function in an adult non-diabetic population, we analysed the association of serum HbA1c levels with endothelial function. Methods: We studied cross-sectional data from 1384 subjects (696 women), aged 25–85, without diabetes, from the population-based Study of Health in Pomerania (SHIP-1). Flow-mediated dilation (FMD) and nitrate-mediated dilation (NMD) measurements of the brachial artery were performed using standardised ultrasound techniques. Linear regression models were carried out to assess the association between serum HbA1c levels and FMD/NMD. Results: Multivariable analyses disclosed an inverse association between serum HbA1c levels and FMD in women, but not in men. In women without current use of antihypertensive medication, increasing serum HbA1c levels were associated with decreasing FMD levels after adjustment for age, body mass index, smoking status, hypertension, low-density lipoprotein cholesterol, and sex-hormone medication (β =−1.17; 95% CI −2.03; −0.30, p =0.009). There was an inverse association between serum HbA1c levels and NMD in men (β =−1.68; 95% CI −2.83; −0.52, p =0.005), but not in women. Conclusion: We conclude that higher serum HbA1c levels in non-diabetic subjects are inversely associated with FMD in women without antihypertensive medication, but not in men. The gender-specific aspects concerning the association of HbA1c levels and NMD in this population should be investigated in further studies. Our results support current considerations that subclinical disorders of glucose metabolism measured by serum HbA1c are associated with subclinical cardiovascular diseases detected by FMD, especially in women. [Copyright &y& Elsevier]
Published: 2011
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30. Low serum magnesium concentrations predict increase in left ventricular mass over 5 years independently of common cardiovascular risk factors

Author: Reffelmann, Thorsten, Dörr, Marcus, Ittermann, Till, Schwahn, Christian, Völzke, Henry, Ruppert, Jörg, Robinson, Daniel, and Felix, Stephan B.
Subjects: *MAGNESIUM in the body, *LEFT heart ventricle, *CARDIOVASCULAR diseases risk factors, *EPIDEMIOLOGY, *HYPERTENSION, *CARDIAC hypertrophy, *PATHOLOGICAL physiology, *ECHOCARDIOGRAPHY
Abstract: Abstract: Objective: Left ventricular hypertrophy (LVH) is a significant predictor of adverse cardiovascular events. Experimental studies suggest a pathophysiological role of magnesium (Mg2+) in the development of arterial hypertension and LVH. Methods: In subjects with complete echocardiographic data from the population-based longitudinal “Study of Health in Pomerania” (n =1 348), the difference in left ventricular mass (LVM) over 5 years (echocardiography) was analyzed in relationship to serum Mg2+ at baseline. Results: Mg2+ at baseline (0.790±0.003mmol/l, mean±SEM) inversely correlated with the difference in LVM over 5 years (p <0.0001, females: p <0.002, males: p <0.024). In the lowest Mg2+-quintile (Mg2+ < =0.73mmol/l), LVM (187.4±3.1g at baseline) increased by 14.9±1.2g, while in the highest Mg2+-quintile (Mg2+ > =0.85mmol/l) LVM (186.7±3.4g at baseline) decreased by −0.5±2.8g (p <0.0001 between quintiles). By multivariable analysis including several cardiovascular risk factors and antihypertensive treatment, serum Mg2+ was associated with the increase in LVM at a statistically high significant level (p <0.0001). LVM after 5 years was significantly higher in subjects within the lower Mg2+-quintiles. This association remained highly significant after adjustment for several cardiovascular risk factors including arterial hypertension and diabetes mellitus. Conclusions: Hypomagnesemia is one of the strongest predictors of gain in LVM over the following 5 years. [ABSTRACT FROM AUTHOR]
Published: 2010
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31. Urinary albumin excretion, even within the normal range, predicts an increase in left ventricular mass over the following 5 years.

Author: Reffelmann, Thorsten, Dörr, Marcus, Völzke, Henry, Friedrich, Nele, Krebs, Alexander, Ittermann, Till, and Felix, Stephan B.
Subjects: *URINALYSIS, *EXCRETION, *ALBUMINS, *ALBUMINURIA, *CREATININE, *KIDNEY diseases
Abstract: There is increasing evidence that urinary albumin excretion, even when below the accepted threshold values for normal excretion, may have significant impact on future cardiovascular risks. To further define this, a total of 1086 patients, aged 45 years and older from the population-based, longitudinal ‘Study of Health in Pomerania’ were evaluated. Patients had echocardiographic analysis at baseline and 5-year follow-up, and were grouped into quartiles according to their baseline urinary albumin-to-creatinine ratio. At baseline, left ventricular mass in the first three quartiles was similar; however, the fourth quartile was significantly elevated and further increased over the 5-year follow-up. In the first quartile, the albumin-to-creatinine ratio and left ventricular mass did not significantly change over 5 years. In the second and third quartiles, the left ventricular mass progressively increased and was significantly correlated with the albumin-to-creatinine ratio. In multivariable analysis, this association was independent of other common cardiovascular risk factors and applicable to both genders. Our study found that the urinary albumin-to-creatinine ratio, even below the current threshold for definition of microalbuminuria, is significantly associated with increased left ventricular mass. [ABSTRACT FROM AUTHOR]
Published: 2010
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32. Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries

Author: Rico Rueedi, Yuri Milaneschi, Brenda W.J.H. Penninx, Neil Poulter, Karen Schwander, Marco Brumat, Kenneth Rice, Yize Li, Veronique Vitart, Ioanna Ntalla, Michele K. Evans, Jeffrey R. O'Connell, Nilesh J. Samani, Colleen M. Sitlani, W. James Gauderman, Xuan Deng, Paul M. Ridker, Yun J. Sung, Yukihide Momozawa, Archie Campbell, Tin Louie, Nona Sotoodehnia, Yii-Der Ida Chen, Cornelia M. van Duijn, Tanika N. Kelly, Peter S. Sever, André G. Uitterlinden, Brigitte Kühnel, John M. Starr, Lawrence F. Bielak, Christopher P. Nelson, Wanqing Wen, Stephan B. Felix, Stefan Weiss, Daniel Levy, Nicholette D. Palmer, Alisa K. Manning, Salman M. Tajuddin, Jill M. Norris, Marie Loh, M. Abdullah Said, Alena Stančáková, Anuradhani Kasturiratne, John M. C. Connell, Jian'an Luan, Tuomas O. Kilpeläinen, Amy R. Bentley, Stephen Sidney, Alan B. Zonderman, Karin Leander, David J. Porteous, Jianjun Liu, Tin Aung, Charles B. Eaton, Sharon L.R. Kardia, Rajkumar Dorajoo, Stephen Turner, Michael Boehnke, Diane M. Becker, Cora E. Lewis, Ozren Polasek, Mickaël Canouil, Kurt Lohman, Georg Ehret, Sarah E. Harris, Robert A. Scott, Claude Bouchard, Lynne E. Wagenknecht, Mohsen Ghanbari, Stephen B. Kritchevsky, Jin-Fang Chai, Gregory L. Burke, Jiang He, Federica Laguzzi, Michael R. Brown, Walter Palmas, Lili Milani, Thomas T. Perls, Tibor V. Varga, José Eduardo Krieger, Erin B. Ware, Tamara B. Harris, Tomohiro Katsuya, Nicole Schupf, Mika Kähönen, Nana Matoba, Hugues Aschard, Ilaria Gandin, Jennifer A. Smith, Traci M. Bartz, James Scott, Tuomo Rankinen, Yuan Shi, Meian He, Timo A. Lakka, Helen R. Warren, Mike A. Nalls, Kent D. Taylor, Woon-Puay Koh, Ya Xing Wang, Muhammad Riaz, Sandosh Padmanabhan, Mary F. Feitosa, Jost B. Jonas, Paul Elliott, Christian Gieger, Terho Lehtimäki, Kaare Christensen, Maris Alver, Pirjo Komulainen, Pamela J. Schreiner, M. Arfan Ikram, David R. Weir, Charles Kooperberg, Oscar H. Franco, Yongmei Liu, Lisa de las Fuentes, Nancy L. Pedersen, Thomas W. Winkler, Bruna Gigante, Göran Hallmans, Ingrid B. Borecki, Shiow Lin, Ian J. Deary, Wei Zheng, Yajuan Wang, Bernardo L. Horta, Heather M. Stringham, Bruce M. Psaty, Paul W. Franks, Weihua Zhang, Nora Franceschini, Adolfo Correa, Nita G. Forouhi, Xiuqing Guo, Fumihiko Takeuchi, L. Adrienne Cupples, William R. Scott, Zoltán Kutalik, He Gao, Nicholas J. Wareham, E. Shyong Tai, Aravinda Chakravarti, C. Charles Gu, Paolo Gasparini, Albertine J. Oldehinkel, Xueling Sim, Norihiro Kato, Evangelos Evangelou, Philippe Froguel, Colin A. McKenzie, Qing Duan, Aldi T. Kraja, Carsten Oliver Schmidt, Bamidele O. Tayo, Xiaofeng Zhu, Thomas Meitinger, Mary K. Wojczynski, Markku Laakso, Mark J. Caulfield, Carl D. Langefeld, Jingzhong Ding, Yechiel Friedlander, Tien Yin Wong, Virginia Fisher, Raymond Noordam, Caizheng Yu, Pim van der Harst, Yik Ying Teo, Ervin R. Fox, Sabanayagam Charumathi, Jonathan Marten, Nicholas Y.Q. Tan, Jerome I. Rotter, Harold Snieder, Karen L. Mohlke, Christine Williams, Olli T. Raitakari, Renée de Mutsert, Lihua Wang, Kathryn Roll, Jingmin Liu, Dongfeng Gu, Wei Zhao, Lynda M. Rose, Michael A. Province, Fernando Pires Hartwig, Rob M. van Dam, Barry I. Freedman, Andres Metspalu, Donald W. Bowden, Andrea R. V. R. Horimoto, Martin Farrall, Frits R. Rosendaal, Rainer Rauramaa, Konstantin Strauch, Albert V. Smith, Yanick Hagemeijer, Michiaki Kubo, Ilja M. Nolte, Tõnu Esko, Yih Chung Tham, Cathy C. Laurie, Antonietta Robino, Anne U. Jackson, Chuan Gao, Dabeeru C. Rao, Xiao-Ou Shu, H. Janaka de Silva, Morris J. Brown, Alanna C. Morrison, Peter J. van der Most, Jian-Min Yuan, Melanie Waldenberger, Leslie J. Raffel, Ulrich John, Fang-Chi Hsu, Reedik Mägi, Solomon K. Musani, Chiea Chuen Khor, Mario Sims, Ruben N. Eppinga, Melissa A. Richard, Yoichiro Kamatani, Changwei Li, Qiuyin Cai, Daniel I. Chasman, Mathilde Boissel, Claudia Langenberg, Sami Heikkinen, Jasmin Divers, Saima Afaq, Wen Bin Wei, Jaspal S. Kooner, Terrence Forrester, Hua Tang, Charles N. Rotimi, Anuj Goel, Annette Peters, Tangchun Wu, Dennis O. Mook-Kanamori, Caroline Hayward, Ching-Yu Cheng, Lisa R. Yanek, Ananda R. Wickremasinghe, Chew-Kiat Heng, Myriam Fornage, Dina Vojinovic, Najaf Amin, Lenore J. Launer, Hugh Watkins, Johanna Kuusisto, Jing Hua Zhao, Barbara V. Howard, Vilmundur Gudnason, Ulrich Broeckel, Eric Boerwinkle, Saskia P. Hagenaars, Dan E. Arking, Peter Vollenweider, Alexandre C. Pereira, Jie Yao, Makoto Hirata, Patricia B. Munroe, Patricia A. Peyser, Jessica D. Faul, Xu Chen, Patrik K. E. Magnusson, John C. Chambers, Tamar Sofer, Marzyeh Amini, Benjamin Lehne, Epidemiology, Erasmus MC other, Neurology, Radiology & Nuclear Medicine, Internal Medicine, Læknadeild (HÍ), Faculty of Medicine (UI), School of Health Sciences (UI), Heilbrigðisvísindasvið (HÍ), Háskóli Íslands (HÍ), University of Iceland (UI), Life Course Epidemiology (LCE), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Cardiovascular Centre (CVC), Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), Brigham and Women's Hospital [Boston], Harvard Medical School [Boston] (HMS), University of Regensburg, Queen Mary University of London (QMUL), Harbor UCLA Medical Center [Torrance, Ca.], Department of Epidemiology, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC)-University of North Carolina System (UNC)-UNC Gillings School of Global Public Health-Carolina Center for Genome Sciences, Northwestern Polytechnical University [Xi'an] (NPU), Centre for Molecular Epidemiology, National University of Singapore (NUS), Harvard School of Public Health, Centre de Bioinformatique, Biostatistique et Biologie Intégrative (C3BI), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), European Genomic Institute for Diabetes - FR 3508 (EGID), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP), National Institutes of Health [Bethesda] (NIH), The following authors declare commercial private and/or governmental affiliations: Bruce M. Psaty (BMP) serves on the DSMB of a clinical trial funded by Zoll Lifecor and on the Steering Committee of the Yale Open Data Access Project funded by Johnson & Johnson. Barbara V. Howard (BVH) has a contract from National Heart, Lung, and Blood Institute (NHLBI). Brenda W.J.H. Penninx (BWJHP) has received research funding (non-related to the work reported here) from Jansen Research and Boehringer Ingelheim. Mike A. Nalls (MAN) is supported by a consulting contract between Data Tecnica International LLC and the National Institute on Aging (NIA), National Institutes of Health (NIH), Bethesda, MD, USA. MAN also consults for Illumina Inc., the Michael J. Fox Foundation, and the University of California Healthcare. MAN also has commercial affiliation with Data Tecnica International, Glen Echo, MD, USA. Mark J. Caulfield (MJC) has commercial affiliation and is Chief Scientist for Genomics England, a UK government company. Oscar H Franco (OHF) is supported by grants from Metagenics (on women's health and epigenetics) and from Nestlé (on child health). Peter S. Sever (PSS) is financial supported from several pharmaceutical companies which manufacture either blood pressure lowering or lipid lowering agents, or both, and consultancy fees. Paul W. Franks (PWF) has been a paid consultant in the design of a personalized nutrition trial (PREDICT) as part of a private-public partnership at Kings College London, UK, and has received research support from several pharmaceutical companies as part of European Union Innovative Medicines Initiative (IMI) projects. Fimlab LTD provided support in the form of salaries for author Terho Lehtimäki (TL) but did not have any additional role in the study design to publish, or preparation of the manuscript. Gen‐info Ltd provided support in the form of salaries for author Ozren Polašek (OP) but did not have any additional role in the study design to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section. There are no patents, products in development, or marked products to declare. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript., AGES (Age Gene/Environment Susceptibility Reykjavik Study) is approved by the Icelandic National Bioethics Committee, VSN: 00–063. The researchers are indebted to the participants for their willingness to participate in the study. ARIC (Atherosclerosis Risk in Communities): The authors thank the staff and participants of the ARIC study for their important contributions. CARDIA (Coronary Artery Risk Development in Young Adults): This manuscript has been reviewed and approved by CARDIA for scientific content. CHS (Cardiovascular Health Study): A full list of principal CHS investigators and institutions can be found at CHS-NHLBI.org. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. IGMM (Institute of Genetics and Molecular Medicine): CROATIA-Korcula: We would like to acknowledge the staff of several institutions in Croatia that supported the field work, including but not limited to The University of Split and Zagreb Medical Schools and the Croatian Institute for Public Health. We would like to acknowledge the invaluable contributions of the recruitment team in Korcula, the administrative teams in Croatia and Edinburgh and the participants. The SNP genotyping for the CROATIA-Korcula cohort was performed in Helmholtz Zentrum München, Neuherberg, Germany. CROATIA-Vis: We would like to acknowledge the staff of several institutions in Croatia that supported the field work, including but not limited to The University of Split and Zagreb Medical Schools, the Institute for Anthropological Research in Zagreb and Croatian Institute for Public Health. The SNP genotyping for the CROATIA-Vis cohort was performed in the core genotyping laboratory of the Wellcome Trust Clinical Research Facility at the Western General Hospital, Edinburgh, Scotland. GS:SFHS: Generation Scotland received core support from the Chief Scientist Office of the Scottish Government Health Directorates [CZD/16/6] and the Scottish Funding Council [HR03006]. Genotyping of the GS:SFHS samples was carried out by the Genetics Core Laboratory at the Wellcome Trust Clinical Research Facility, Edinburgh, Scotland. ERF (Erasmus Rucphen Family study): We are grateful to all study participants and their relatives, general practitioners and neurologists for their contributions and to P. Veraart for her help in genealogy, J. Vergeer for the supervision of the laboratory work, P. Snijders for his help in data collection and E.M. van Leeuwen for genetic imputation. GENOA (Genetic Epidemiology Network of Arteriopathy): Genotyping was performed at the Mayo Clinic (Stephen T. Turner, MD, Mariza de Andrade PhD, Julie Cunningham, PhD). We thank Eric Boerwinkle, PhD and Megan L. Grove from the Human Genetics Center and Institute of Molecular Medicine and Division of Epidemiology, University of Texas Health Science Center, Houston, Texas, USA for their help with genotyping. We would also like to thank the families that participated in the GENOA study. HANDLS (Healthy Aging in Neighborhoods of Diversity across the Life Span): Data analyses for the HANDLS study utilized the high-performance computational resources of the Biowulf Linux cluster at the National Institutes of Health, Bethesda, MD. http://hpc.nih.gov HUFS (Howard University Family Study): We thank the participants of the study. The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official view of the National Institutes of Health. HyperGEN (Hypertension Genetic Epidemiology Network): The study involves: University of Utah: (Network Coordinating Center, Field Center, and Molecular Genetics Lab), Univ. of Alabama at Birmingham: (Field Center and Echo Coordinating and Analysis Center), Medical College of Wisconsin: (Echo Genotyping Lab), Boston University: (Field Center), University of Minnesota: (Field Center and Biochemistry Lab), University of North Carolina: (Field Center), Washington University: (Data Coordinating Center), Weil Cornell Medical College: (Echo Reading Center), National Heart, Lung, & Blood Institute. For a complete list of HyperGEN Investigators: http://www.biostat.wustl.edu/hypergen/Acknowledge.html JHS (Jackson Heart Study): The authors wish to thank the staffs and participants of the JHS. MESA (Multi-Ethnic Study of Atherosclerosis): MESA and the MESA SHARe project are conducted in collaboration with MESA investigators. Genotyping was performed at Affymetrix (Santa Clara, California, USA) and the Broad Institute of Harvard and MIT (Boston, Massachusetts, USA) using the Affymetrix Genome-Wide Human SNP Array 6.0. NEO (The Netherlands Epidemiology of Obesity study): The authors of the NEO study thank all individuals who participated in the Netherlands Epidemiology in Obesity study, all participating general practitioners for inviting eligible participants and all research nurses for collection of the data. We thank the NEO study group, Petra Noordijk, Pat van Beelen and Ingeborg de Jonge for the coordination, lab and data management of the NEO study. RS (Rotterdam Study) was funded by Erasmus Medical Center and Erasmus University, Rotterdam, Netherlands Organization for the Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam. The authors are grateful to the study participants, the staff from the Rotterdam Study and the participating general practitioners and pharmacists. The generation and management of GWAS genotype data for the Rotterdam Study was executed by the Human Genotyping Facility of the Genetic Laboratory of the Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands. We thank Pascal Arp, Mila Jhamai, Marijn Verkerk, Lizbeth Herrera, Marjolein Peters and Carolina Medina-Gomez for their help in creating the GWAS database, and Karol Estrada, Yurii Aulchenko and Carolina Medina-Gomez for the creation and analysis of imputed data. WHI (Women’s Health Initiative): The authors thank the WHI investigators and staff for their dedication, and the study participants for making the program possible. A full listing of WHI investigators can be found at: http://www.whi.org/researchers/Documents%20%20Write%20a%20Paper/WHI%20Investigator%20Short%20List.pdf Replication: AA-DHS (African American Diabetes Heart Study): The investigators acknowledge the cooperation of our Diabetes Heart Study (DHS) and AA-DHS participants. ASCOT (Anglo-Scandinavian Cardiac Outcomes Trial): We thank all ASCOT trial participants, physicians, nurses, and practices in the participating countries for their important contribution to the study. In particular, we thank Clare Muckian and David Toomey for their help in DNA extraction, storage, and handling. We would also like to acknowledge the Barts and The London Genome Centre staff for genotyping the Exome chip array. P.B.M, M.J.C and H.R.W wish to acknowledge the support of the NIHR Cardiovascular Biomedical Research Centre at Barts and Queen Mary University of London, UK. BBJ (Biobank Japan Project): We thank all the participants, medical coordinators of the cooperating hospitals for collecting samples and clinical information in the project. BRIGHT (British Genetics of Hypertension): The BRIGHT study is extremely grateful to all the patients who participated in the study and the BRIGHT nursing team. P.B.M, M.J.C and H.R.W wish to acknowledge the support of the NIHR Cardiovascular Biomedical Research Centre at Barts and Queen Mary University of London, UK. CoLaus (Cohorte Lausannoise Study): The authors would like to thank all the people who participated in the recruitment of the participants, data collection and validation, particularly Nicole Bonvin, Yolande Barreau, Mathieu Firmann, François Bastardot, Julien Vaucher, Panagiotis Antiochos and Cédric Gubelmann. DESIR (Data from an Epidemiological Study on the Insulin Resistance): The DESIR Study Group is composed of Inserm-U1018 (Paris: B. Balkau, P. Ducimetière, E. Eschwège), Inserm-U367 (Paris: F. Alhenc-Gelas), CHU d’Angers (A. Girault), Bichat Hospital (Paris: F. Fumeron, M. Marre, R. Roussel), CHU de Rennes (F. Bonnet), CNRS UMR-8199 (Lille: A. Bonnefond, P. Froguel), Medical Examination Services (Alençon, Angers, Blois, Caen, Chartres, Chateauroux, Cholet, LeMans, Orléans and Tours), Research Institute for General Medicine (J. Cogneau), the general practitioners of the region and the Cross- Regional Institute for Health (C. Born, E. Caces, M. Cailleau, N. Copin, J.G. Moreau, F. Rakotozafy, J. Tichet, S. Vol). DHS (Diabetes Heart Study): The authors thank the investigators, staff, and participants of the DHS for their valuable contributions. EGCUT Estonian Genome Center—University of Tartu (Estonian Biobank): Data analyzes were carried out in part in the High Performance Computing Center of University of Tartu. EPIC (European Prospective Investigation into Cancer and Nutrition)-Norfolk: We thank all EPIC participants and staff for their contribution to the study. FENLAND (The Fenland Study): We are grateful to all the volunteers for their time and help, and to the General Practitioners and practice staff for assistance with recruitment. We thank the Fenland Study Investigators, Fenland Study Co-ordination team and the Epidemiology Field, Data and Laboratory teams. We further acknowledge support from the Medical research council (MC_UU_12015/1). GeneSTAR (Genetic Studies of Atherosclerosis Risk): We are very grateful to all of our participants for their long-term involvement. GLACIER (Gene x Lifestyle Interactions and Complex Traits Involved in Elevated Disease Risk): We thank the participants, health professionals and data managers involved in the Västerbottens Intervention Project. We are also grateful to the staff of the Northern Sweden Biobank for preparing materials and to K Enqvist and T Johansson (Västerbottens County Council, Umeå, Sweden) for DNA preparation. HCHS/SOL (Hispanic Community Health Study/Study of Latinos): We thank the participants and staff of the HCHS/SOL study for their contributions to this study. HRS (Health & Retirement Study): Our genotyping was conducted by the NIH Center for Inherited Disease Research (CIDR) at Johns Hopkins University. Genotyping quality control and final preparation of the data were performed by the Genetics Coordinating Center at the University of Washington. HyperGEN-AXIOM (Hypertension Genetic Epidemiology Network—Axiom Chip GWAS): We thank the study investigators, staff and participants for their value contributions. INGI (Italian Network Genetic Isolate): We thank all the inhabitants who participated to the projects. InterAct (The EPIC-InterAct Case-Cohort Study): We thank all EPIC participants and staff for their contribution to the study. IRAS (Insulin Resistance Atherosclerosis Study): The authors thank study investigators, staff, and participants for their valuable contributions. KORA (Cooperative Health Research in the Augsburg Region): We thank all KORA participants and staff for their contribution to the study. LBC1921 (Lothian Birth Cohort 1921): We thank the LBC1921 cohort participants and team members who contributed to these studies. Funding from the Biological Sciences Research Council (BBSRC) and Medical Research Council (MRC) is gratefully acknowledged. LBC1936 (Lothian Birth Cohort 1936): We thank the LBC1936 cohort participants and team members who contributed to these studies. Funding from the Biological Sciences Research Council (BBSRC) and Medical Research Council (MRC) is gratefully acknowledged. LifeLines (Lifelines Cohort Study): The authors wish to acknowledge the services of the Lifelines, the contributing research centers delivering data to Lifelines, and all the study participants. The authors wish to acknowledge the services of the Lifelines, the contributing research centers delivering data to Lifelines, and all the study participants. Also, Lifelines acknowledges the contributions from Behrooz Z Alizadeh (Department of Epidemiology, University of Groningen, University Medical Center Groningen, The Netherlands), H Marike Boezen (Department of Epidemiology, University of Groningen, University Medical Center Groningen, The Netherlands), Lude Franke (Department of Genetics, University of Groningen, University Medical Center Groningen, The Netherlands), Pim van der Harst (Department of Cardiology, University of Groningen, University Medical Center Groningen, The Netherlands), Gerjan Navis (Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, The Netherlands), Marianne Rots (Department of Medical Biology, University of Groningen, University Medical Center Groningen, The Netherlands), Harold Snieder (Department of Epidemiology, University of Groningen, University Medical Center Groningen, The Netherlands), Morris Swertz (Department of Genetics, University of Groningen, University Medical Center Groningen, The Netherlands), Bruce HR Wolffenbuttel (Department of Endocrinology, University of Groningen, University Medical Center Groningen, The Netherlands), Cisca Wijmenga (Department of Genetics, University of Groningen, University Medical Center Groningen, The Netherlands). LLFS (Long Life Family Study): The LLFS would like to thank the participants and research staff who make the study possible. LOLIPOP (London Life Sciences Prospective Population Study): We acknowledge support of the MRC-PHE Centre for Environment and Health, and the NIHR Health Protection Research Unit on Health Impact of Environmental Hazards. The work was carried out in part at the NIHR/Wellcome Trust Imperial Clinical Research Facility. The views expressed are those of the author(s) and not necessarily those of the Imperial College Healthcare NHS Trust, the NHS, the NIHR or the Department of Health. We thank the participants and research staff who made the study possible. PROCARDIS (Precocious Coronary Artery Disease): The PROCARDIS researchers thank the patients for their selfless participation in this project. RHS (Ragama Health Study): The RHS was supported by the Grant of National Center for Global Health and Medicine (NCGM), Japan. SWHS/SMHS (Shanghai Women's Health Study/ Shanghai Men's Health Study): We thank all the individuals who took part in these studies and all the researchers who have enabled this work to be carried out. TRAILS (TRacking Adolescents’ Individual Lives Survey): TRAILS is a collaborative project involving various departments of the University Medical Center and University of Groningen, the Erasmus University Medical Center Rotterdam, the University of Utrecht, the Radboud Medical Center Nijmegen, and the Parnassia Bavo group, all in the Netherlands. We are grateful to all adolescents who participated in this research and to everyone who worked on this project and made it possible. UKB (United Kingdom Biobank, www.ukbiobank.ac.uk): This research has been conducted using the UK Biobank Resource. The UK Biobank data were analyzed from the data set corresponding to UK Biobank access application no. 236, application title 'Genome-wide association study of blood pressure', with Paul Elliott as the PI/applicant. This work was supported by the UK-CMC and the BP working group., InterAct Consortium, Marten, Jonathan [0000-0001-6916-2014], Luan, Jian'an [0000-0003-3137-6337], Zhao, Jing Hua [0000-0003-4930-3582], Forouhi, Nita [0000-0002-5041-248X], Langenberg, Claudia [0000-0002-5017-7344], Wareham, Nicholas [0000-0003-1422-2993], Apollo - University of Cambridge Repository, Lee Kong Chian School of Medicine (LKCMedicine), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 (EGID), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Feitosa, Mary F., Kraja, Aldi T., Chasman, Daniel I., Sung, Yun J., Winkler, Thomas W., Ntalla, Ioanna, Guo, Xiuqing, Franceschini, Nora, Cheng, Ching-Yu, Sim, Xueling, Vojinovic, Dina, Marten, Jonathan, Musani, Solomon K., Li, Changwei, Bentley, Amy R., Brown, Michael R., Schwander, Karen, Richard, Melissa A., Noordam, Raymond, Aschard, Hugue, Bartz, Traci M., Bielak, Lawrence F., Dorajoo, Rajkumar, Fisher, Virginia, Hartwig, Fernando P., Horimoto, Andrea R. V. R., Lohman, Kurt K., Manning, Alisa K., Rankinen, Tuomo, Smith, Albert V., Tajuddin, Salman M., Wojczynski, Mary K., Alver, Mari, Boissel, Mathilde, Cai, Qiuyin, Campbell, Archie, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Gao, Chuan, Goel, Anuj, Hagemeijer, Yanick, Harris, Sarah E., He, Meian, Hsu, Fang-Chi, Jackson, Anne U., Kähönen, Mika, Kasturiratne, Anuradhani, Komulainen, Pirjo, Kühnel, Brigitte, Laguzzi, Federica, Luan, Jian'An, Matoba, Nana, Nolte, Ilja M., Padmanabhan, Sandosh, Riaz, Muhammad, Rueedi, Rico, Robino, Antonietta, Said, M. Abdullah, Scott, Robert A., Sofer, Tamar, Stančáková, Alena, Takeuchi, Fumihiko, Tayo, Bamidele O., Van Der Most, Peter J., Varga, Tibor V., Vitart, Veronique, Wang, Yajuan, Ware, Erin B., Warren, Helen R., Weiss, Stefan, Wen, Wanqing, Yanek, Lisa R., Zhang, Weihua, Zhao, Jing Hua, Afaq, Saima, Amin, Najaf, Amini, Marzyeh, Arking, Dan E., Aung, Tin, Boerwinkle, Eric, Borecki, Ingrid, Broeckel, Ulrich, Brown, Morri, Brumat, Marco, Burke, Gregory L., Canouil, Mickaël, Chakravarti, Aravinda, Charumathi, Sabanayagam, Chen, Yii-Der Ida, Connell, John M., Correa, Adolfo, De Las Fuentes, Lisa, De Mutsert, Renée, De Silva, H. Janaka, Deng, Xuan, Ding, Jingzhong, Duan, Qing, Eaton, Charles B., Ehret, Georg, Eppinga, Ruben N., Evangelou, Evangelo, Faul, Jessica D., Felix, Stephan B., Forouhi, Nita G., Forrester, Terrence, Franco, Oscar H., Friedlander, Yechiel, Gandin, Ilaria, Gao, He, Ghanbari, Mohsen, Gigante, Bruna, Gu, C. Charle, Gu, Dongfeng, Hagenaars, Saskia P., Hallmans, Göran, Harris, Tamara B., He, Jiang, Heikkinen, Sami, Heng, Chew-Kiat, Hirata, Makoto, Howard, Barbara V., Ikram, M. Arfan, John, Ulrich, Katsuya, Tomohiro, Khor, Chiea Chuen, Kilpeläinen, Tuomas O., Koh, Woon-Puay, Krieger, José E., Kritchevsky, Stephen B., Kubo, Michiaki, Kuusisto, Johanna, Lakka, Timo A., Langefeld, Carl D., Langenberg, Claudia, Launer, Lenore J., Lehne, Benjamin, Lewis, Cora E., Li, Yize, Lin, Shiow, Liu, Jianjun, Liu, Jingmin, Loh, Marie, Louie, Tin, Mägi, Reedik, Mckenzie, Colin A., Meitinger, Thoma, Metspalu, Andre, Milaneschi, Yuri, Milani, Lili, Mohlke, Karen L., Momozawa, Yukihide, Nalls, Mike A., Nelson, Christopher P., Sotoodehnia, Nona, Norris, Jill M., O'Connell, Jeff R., Palmer, Nicholette D., Perls, Thoma, Pedersen, Nancy L., Peters, Annette, Peyser, Patricia A., Poulter, Neil, Raffel, Leslie J., Raitakari, Olli T., Roll, Kathryn, Rose, Lynda M., Rosendaal, Frits R., Rotter, Jerome I., Schmidt, Carsten O., Schreiner, Pamela J., Schupf, Nicole, Scott, William R., Sever, Peter S., Shi, Yuan, Sidney, Stephen, Sims, Mario, Sitlani, Colleen M., Smith, Jennifer A., Snieder, Harold, Starr, John M., Strauch, Konstantin, Stringham, Heather M., Tan, Nicholas Y. Q., Tang, Hua, Taylor, Kent D., Teo, Yik Ying, Tham, Yih Chung, Turner, Stephen T., Uitterlinden, André G., Vollenweider, Peter, Waldenberger, Melanie, Wang, Lihua, Wang, Ya Xing, Wei, Wen Bin, Williams, Christine, Yao, Jie, Yu, Caizheng, Yuan, Jian-Min, Zhao, Wei, Zonderman, Alan B., Becker, Diane M., Boehnke, Michael, Bowden, Donald W., Chambers, John C., Deary, Ian J., Esko, Tõnu, Farrall, Martin, Franks, Paul W., Freedman, Barry I., Froguel, Philippe, Gasparini, Paolo, Gieger, Christian, Jonas, Jost Bruno, Kamatani, Yoichiro, Kato, Norihiro, Kooner, Jaspal S., Kutalik, Zoltán, Laakso, Markku, Laurie, Cathy C., Leander, Karin, Lehtimäki, Terho, Magnusson, Patrik K. E., Oldehinkel, Albertine J., Penninx, Brenda W. J. H., Polasek, Ozren, Porteous, David J., Rauramaa, Rainer, Samani, Nilesh J., Scott, Jame, Shu, Xiao-Ou, Van Der Harst, Pim, Wagenknecht, Lynne E., Wareham, Nicholas J., Watkins, Hugh, Weir, David R., Wickremasinghe, Ananda R., Wu, Tangchun, Zheng, Wei, Bouchard, Claude, Christensen, Kaare, Evans, Michele K., Gudnason, Vilmundur, Horta, Bernardo L., Kardia, Sharon L. R., Liu, Yongmei, Pereira, Alexandre C., Psaty, Bruce M., Ridker, Paul M., Van Dam, Rob M., Gauderman, W. Jame, Zhu, Xiaofeng, Mook-Kanamori, Dennis O., Fornage, Myriam, Rotimi, Charles N., Cupples, L. Adrienne, Kelly, Tanika N., Fox, Ervin R., Hayward, Caroline, Van Duijn, Cornelia M., Tai, E. Shyong, Wong, Tien Yin, Kooperberg, Charle, Palmas, Walter, Rice, Kenneth, Morrison, Alanna C., Elliott, Paul, Caulfield, Mark J., Munroe, Patricia B., Rao, Dabeeru C., Province, Michael A., Levy, Daniel, Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, Surgery, APH - Mental Health, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Digital Health, and Ehret, Georg Benedikt
Subjects: Genetics and Molecular Biology (all), Male, Erfðagreining, Áfengissýki, LOCI, Social Sciences, Blood Pressure, Genome-wide association study, Biochemistry, Vascular Medicine, TRANSCRIPTION FACTOR GATA4, Biochemistry, Genetics and Molecular Biology (all), Agricultural and Biological Sciences (all), DEPENDENCE, HEPATOCELLULAR-CARCINOMA, 80 and over, Psychology, Public and Occupational Health, Alcohol consumption, Cardiac and Cardiovascular Systems, Gene–environment interaction, ddc:616, Aged, 80 and over, [STAT.AP]Statistics [stat]/Applications [stat.AP], MESH: Middle Aged, Kardiologi, MESH: Polymorphism, Single Nucleotide, Áfengisneysla, MESH: Gene-Environment Interaction, COMMON VARIANTS, Genomics, MESH: Blood Pressure, Pedigree, 3. Good health, Näringslära, MESH: Young Adult, Physical Sciences, Medicine, Medical genetics, Erfðarannsóknir, Statistics (Mathematics), medicine.medical_specialty, Blood Pressure/genetics, Alcohol Drinking, MESH: Pedigree, Science, Genetic loci, ta3111, Genome Complexity, 03 medical and health sciences, Gene mapping, Genetics, Humans, Polymorphism, Statistical Methods, GENOME-WIDE ASSOCIATION, Molecular Biology Techniques, Molecular Biology, Alleles, Aged, MESH: Adolescent, MESH: Humans, Adolescent, Adult, Alcohol Drinking/epidemiology, Alcohol Drinking/genetics, Cohort Studies, Continental Population Groups/genetics, Continental Population Groups/statistics & numerical data, Female, Gene-Environment Interaction, Genetic Predisposition to Disease/epidemiology, Genetic Predisposition to Disease/genetics, Genome-Wide Association Study, Hypertension/epidemiology, Hypertension/genetics, Middle Aged, Polymorphism, Single Nucleotide, Young Adult, Gene Mapping, Racial Groups, ta1182, Biology and Life Sciences, Computational Biology, MESH: Adult, Meta-analysis, 030104 developmental biology, Genetic Loci, MESH: Genome-Wide Association Study, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], MESH: Female, Mathematics, MESH: Alcohol Drinking, Meta-Analysis, 0301 basic medicine, MESH: Continental Population Groups, MESH: Hypertension, Mathematical and Statistical Techniques, MESH: Aged, 80 and over, Polymorphism (computer science), Medicine and Health Sciences, FUNCTIONAL VARIATION, MESH: Cohort Studies, MESH: Aged, Alcohol Consumption, Multidisciplinary, Nutrition and Dietetics, MESH: Genetic Predisposition to Disease, Genetic Predisposition to Disease/epidemiology/genetics, Single Nucleotide, Blóðþrýstingur, ENVIRONMENT INTERACTION, PTP4A1-PHF3-EYS VARIANTS, Alcoholism, ANCESTRAIS, Háþrýstingur, Hypertension, Blood pressure, [STAT.ME]Statistics [stat]/Methodology [stat.ME], Medical Genetics, Research Article, Substance-Related Disorders, Addiction, RISK, METAANALYSIS, Research and Analysis Methods, Mental Health and Psychiatry, medicine, Medicine [Science], Genetic Predisposition to Disease, Allele, Hypertension/epidemiology/genetics, Nutrition, Medicinsk genetik, Continental Population Groups/genetics/statistics & numerical data, business.industry, Alcohol Drinking/epidemiology/genetics, Genetic architecture, MESH: Male, Introns, Diet, BODY-MASS INDEX, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract: Publisher's version (útgefin grein)., Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in ≈131K individuals across several ancestry groups yielded 3,514 SNVs (245 loci) with suggestive evidence of association (P < 1.0 x 10−5). In Stage 2, these SNVs were tested for independent external replication in ≈440K individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2,159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 x 10−8). For African ancestry samples, we detected 18 potentially novel BP loci (P < 5.0 x 10−8) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2) have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension., The following authors declare commercial private and/or governmental affiliations: Bruce M. Psaty (BMP) serves on the DSMB of a clinical trial funded by Zoll Lifecor and on the Steering Committee of the Yale Open Data Access Project funded by Johnson & Johnson. Barbara V. Howard (BVH) has a contract from National Heart, Lung, and Blood Institute (NHLBI). Brenda W.J.H. Penninx (BWJHP) has received research funding (non-related to the work reported here) from Jansen Research and Boehringer Ingelheim. Mike A. Nalls (MAN) is supported by a consulting contract between Data Tecnica International LLC and the National Institute on Aging (NIA), National Institutes of Health (NIH), Bethesda, MD, USA. MAN also consults for Illumina Inc., the Michael J. Fox Foundation, and the University of California Healthcare. MAN also has commercial affiliation with Data Tecnica International, Glen Echo, MD, USA. Mark J. Caulfield (MJC) has commercial affiliation and is Chief Scientist for Genomics England, a UK government company. Oscar H Franco (OHF) is supported by grants from Metagenics (on women's health and epigenetics) and from Nestlé (on child health). Peter S. Sever (PSS) is financial supported from several pharmaceutical companies which manufacture either blood pressure lowering or lipid lowering agents, or both, and consultancy fees. Paul W. Franks (PWF) has been a paid consultant in the design of a personalized nutrition trial (PREDICT) as part of a private-public partnership at Kings College London, UK, and has received research support from several pharmaceutical companies as part of European Union Innovative Medicines Initiative (IMI) projects. Fimlab LTD provided support in the form of salaries for author Terho Lehtimäki (TL) but did not have any additional role in the study design to publish, or preparation of the manuscript. Gen‐info Ltd provided support in the form of salaries for author Ozren Polašek (OP) but did not have any additional role in the study design to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section. There are no patents, products in development, or marked products to declare. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Published: 2018

33. Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function

Author: Peter Kovacs, Alan F. Wright, Stephen Turner, Michèle M. Sale, Siim Sõber, Janoš Terzić, Elin Org, Richard S. Cooper, Alena Stančáková, Jerome I. Rotter, W. H. Linda Kao, Albert Hofman, Andrew B. Singleton, Florian Kronenberg, Jianjun Liu, Nicole L. Glazer, Christopher W. Knouff, Jennifer L. Bragg-Gresham, Juha Karjalainen, Li Ching Chang, Benjamin J. Wright, Jacqueline C.M. Witteman, Martin G. Larson, Klaus Stark, Richard J. Rodeheffer, Sharon L.R. Kardia, Douglas M. Ruderfer, Sheila Ulivi, Madhumathi Rao, Andrew A. Hicks, Eva Brand, Viviane Nicaud, Stephen G. Ball, Anna Köttgen, Germaine C. Verwoert, Anders Hamsten, Nick Shrine, Uwe Völker, Stefan Kloiber, Stephen Hancock, Emelia J. Benjamin, Bok Ghee Han, Kenneth Rice, Mark Woodward, Veronique Vitart, Karl Andersen, Nicholas J. Wareham, Robert Roberts, Maja Barbalić, David Couper, Yukinori Okada, André G. Uitterlinden, Sekar Kathiresan, Leo-Pekka Lyytikäinen, Pankaj Arora, Tatijana Zemunik, David S. Siscovick, Simonetta Guarrera, Dawn M. Waterworth, Tatjana Stojakovic, Braxton D. Mitchell, Devin Absher, Carmen A. Peralta, Mika Kivimäki, Xueling Sim, Norihiro Kato, Philippe Froguel, Keith L. Keene, Donna K. Arnett, Naoyuki Kamatani, Tazeen H. Jafar, Idris Guessous, Gunnar Jacobs, Michael M. Hoffmann, Kari Stefansson, Christian Hengstenberg, Tomonori Okamura, Inga Prokopenko, Christina Willenborg, Peter S. Braund, Rainer Rettig, Francesco U.S. Mattace-Raso, Vikal Tripathy, F. Gerald R. Fowkes, Laura R. Loehr, Harry Campbell, Margherita Cavalieri, Olle Melander, Hao Mei, I. Mateo Leach, Nicholette D. Palmer, Eva Albrecht, Naoharu Iwai, Stefan Martin Brand, Toshiko Tanaka, Jackie A. Cooper, Omri Gottesman, Manuela Uda, Angelo Scuteri, Aroon D. Hingorani, Cristiano Fava, Yusuke Nakamura, Jiang He, Min Jin Go, Serge Hercberg, Wendy L. McArdle, Philipp S. Wild, Florian Ernst, Paul Mitchell, Wolfgang Koenig, Caroline S. Fox, S. J.Cathy Fann, Janine F. Felix, Anna F. Dominiczak, Mike A. Nalls, Erik Ingelsson, Mario A. Morken, Susana Eyheramendy, Christopher Newton-Cheh, Igor Rudan, D. G. Vinay, Christopher P. Nelson, Ervin R. Fox, Xiuqing Guo, Jing Hua Zhao, Rick Twee-Hee Ong, Margaret M. Redfield, Oscar H. Franco, Yongmei Liu, Fulvio Ricceri, Mark A. Hlatky, Bernhard Paulweber, Mingyao Li, Themistocles L. Assimes, Karl Winkler, Inês Barroso, Sylvia E. Rosas, M Walker, Richard W Morris, Bo Hedblad, Hakon Hakonarson, Sonny Dandona, Peter H. Whincup, Martin Adam, Vilmundur Gudnason, Daniel Ackermann, Qiong Yang, Cuno S. P. M. Uiterwaal, Paul M. Ridker, George Davey Smith, Li Chen, C. Sinning, Terri L. Young, Jer-Yuarn Wu, Walter Palmas, Will Longstreth, Joe Devaney, Pavel Hamet, Xiaofeng Zhu, Fredrik Nyberg, Wilfried Renner, Anuj Goel, L. Adrienne Cupples, Nish Chaturvedi, Iftikhar J. Kullo, Nicholas D. Hastie, Aude Saint-Pierre, Panos Deloukas, Smita R. Kulkarni, Eric Boerwinkle, Wolfram Goessling, Gian Andri Thun, Eric J.G. Sijbrands, Shih-Jen Hwang, Carole Proust, Hirotsugu Ueshima, Kristian Hveem, Pierre Meneton, Joshua C. Denny, Olivier Devuyst, Kerri L. Wiggins, Ming-Huei Chen, Robert W. Lawrence, Robert L. Wilensky, Andre Franke, Nicole Soranzo, Simon Heath, Margot Haun, Karlhans Endlich, David Altshuler, Harald Grallert, Laurence Tiret, Luigi Ferrucci, Caroline Hayward, Sudha Seshadri, Bénédicte Stengel, Lynne E. Wagenknecht, John Attia, Andreas Ziegler, Renate B. Schnabel, Stefan Schreiber, Santosh Dahgam, Kurt Lohman, Christian M. Shaffer, Barbara Ludwig, Katalin Susztak, Chien-Hsiun Chen, Michele K. Evans, Paolo Vineis, Guo Li, Thomas J. Wang, Meena Kumari, Heather M. Stringham, Bruce M. Psaty, Norman Klopp, Halit Ongen, Ben A. Oostra, Stefan Coassin, Petra Bruse, Wei-Min Chen, Unnur Thorsteinsdottir, Charles N. Rotimi, Robert J. Carroll, Muredach P. Reilly, Niek Verweij, Dena G. Hernandez, Amy J. Swift, Barbara Kollerits, Hyung Lae Kim, Cristian Pattaro, Ivana Kolcic, Ronit Katz, John M. C. Connell, Dan E. Arking, Albert W. Dreisbach, Peter Vollenweider, C. S. Janipalli, Jian'an Luan, Erkki Vartiainen, James T. Willerson, John R. Thompson, Daniela Toniolo, Lyle J. Palmer, Alexander Teumer, Serkalem Demissie-Banjaw, Stella Trompet, James E. Hixson, Sue Shaw-Hawkins, Rossella Sorice, Bernhard R. Winkelmann, John Danesh, Anthony J. Balmforth, Toshio Ogihara, Jyotika K. Fernandes, Ulf Gyllensten, Ville Aalto, Åsa Johansson, Andres Metspalu, John F. Peden, Diana Kuh, Medea Imboden, Antonio Lupo, Su Chi Lim, Young-Jin Kim, Giovanni Malerba, Yurii S. Aulchenko, Satoshi Umemura, Ioanna Tzoulaki, Alan B. Weder, Helena Schmidt, Gerjan Navis, Susan R. Heckbert, Hans J. Rupprecht, Edward G. Lakatta, Christian Gieger, Najaf Amin, Paul Muntner, Lenore J. Launer, Ivana Persico, Hugh Watkins, Ian Ford, K. Radha Mani, Sylvia Stracke, Johanna Kuusisto, John Chalmers, Muhammad Islam, Lars Lind, Stefan R. Bornstein, Marjo-Riitta Järvelin, J. H. Young, Reiner Biffar, Santhi K. Ganesh, Kazuhiko Yamamoto, Annette Peters, Linda S. Adair, Tõnu Esko, Rebecca Hardy, Olga Jarinova, Antonietta Robino, Ruth McPherson, Benjamin F. Voight, Anne U. Jackson, Gang Shi, Stefania Bandinelli, Peter J. van der Most, John S. Gottdiener, Ying A. Wang, Mariza de Andrade, Joshua C. Bis, Leslie J. Raffel, Man Li, Jemma C. Hopewell, Bernhard O. Böhm, Aaron R. Folsom, Noël P. Burtt, S. Sidney, Diana Zelenika, Yuri Milaneschi, Pilar Galan, Iris M. Heid, Bernhard K. Krämer, Jean-Michel Gaspoz, Lynda M. Rose, Massimiliano Cocca, Jaap W. Deckers, Martin Farrall, Kent D. Taylor, Albert V. Smith, Candace Guiducci, Alan R. Shuldiner, Shiro Maeda, Liming Qu, Marilyn C. Cornelis, Xiaoling Wang, Daniel Shriner, Jutta Palmen, Yingchang Lu, Heyo K. Kroemer, Pio D'Adamo, Stephan J. L. Bakker, Tamara B. Harris, Myriam Rheinberger, Tetsuro Miki, Audrey Y. Chu, Ramachandran S. Vasan, Fuu Jen Tsai, Jan A. Staessen, Daniel I. Chasman, Jan Stritzke, Jasmin Divers, Meredith C. Foster, Jeanette M. Stafford, Maksim Struchalin, Arne Schillert, Jacques S. Beckmann, Mark E. Cooper, Jean-Charles Lambert, Mario Pirastu, Katja Butterbach, Carl G. P. Platou, Yan V. Sun, Marcus Fischer, Maciej Tomaszewski, Karl Werdan, Peng Chen, Daniel J. Rader, Thomas Münzel, Lowell F. Satler, Tom R. Gaunt, Brenda W.J.H. Penninx, William H. Matthai, John Whitfield, Rita P.S. Middelberg, Margus Viigimaa, Toshihiro Tanaka, Ida Yii Der Chen, Morris J. Brown, Valur Emilsson, J. Viikari, Wolfgang Lieb, Stephen E. Epstein, Harald Dobnig, Aravinda Chakravarti, Patrick Linsel-Nitschke, Stefan Pilz, Angela Doering, Sarah H. Wild, Patricia B. Munroe, Megan E. Rudock, Nicole Probst-Hensch, Danish Saleheen, Diederick E. Grobbee, Anke Tönjes, Narisu Narisu, Annika Rosengren, Masato Isono, Catherine Helmer, M. J.Kranthi Kumar, Alanna C. Morrison, Kay-Tee Khaw, Tanja Zeller, Jeffrey R. O'Connell, Christian Müller, Georg Homuth, Giriraj R. Chandak, Pankaj Sharma, Marcus Dörr, Veikko Salomaa, Paul F. O'Reilly, David Hadley, Hermann Brenner, Paolo Gasparini, Nanette R. Lee, Bamidele O. Tayo, Robert Clarke, Henri Wallaschofski, Marketa Sjögren, Abbas Dehghan, Melanie Waldenberger, Neil Risch, Vasyl Pihur, Jessica D. Faul, François Cambien, Christian Fuchsberger, Nicholas G. Martin, John C. Chambers, Zouhair Aherrahrou, Karl J. Lackner, Leif Groop, Matthias Olden, Wiek H. van Gilst, Mathias Gorski, Yvonne T. van der Schouw, Patrick Diemert, Christoph Bickel, Yik Ying Teo, Giorgio Pistis, Ruth J. F. Loos, Gudrun Veldre, Thorsten Reffelmann, Lude Franke, Karen L. Mohlke, Stefan Blankenberg, Massimo Mangino, Ian N. M. Day, Atsushi Takahashi, Alan B. Zonderman, Hua Tang, Reijo Laaksonen, Holly Kramer, Gary C. Curhan, Adrienne Tin, Talin Haritunians, Loic Yengo, Philip Howard, Arnika Kathleen Wagner, Anna Maria Corsi, Yen Pei C. Chang, Karin Halina Greiser, Jeanette Erdmann, Solveig Gretarsdottir, Sanjay Kinra, Alex Parker, Belen Ponte, Marina Ciullo, Michael Preuss, Tin Aung, Nicholas L. Smith, Michiaki Kubo, Richard N. Bergman, Alan S. Go, Patricia P. Chang, Gudmundur Thorgeirsson, Christa Meisinger, Gonçalo R. Abecasis, Maria Blettner, Jaana Laitinen, Daniel Taliun, Carlos Iribarren, Paavo Zitting, Thomas Lumley, Andreas Meinitzer, Wayne D. Rosamond, Daehee Kang, Johanne Tremblay, Stephan B. Felix, Colin A. McKenzie, Yuan-Tsong Chen, Lyudmyla Kedenko, Mladen Boban, Fadi J. Charchar, Adebowale Adeyemo, Brendan M. Buckley, Jennifer A. Smith, Reinhold Schmidt, Jaspal S. Kooner, Gavin Lucas, Paul Elliott, Dorairajan Prabhakaran, Tune H. Pers, Tunde Salako, Terrence Forrester, Paul Burton, Jeffrey R. Gulcher, Kelly A. Volcik, Richard M. Myers, Andreas Tomaschitz, H.-Erich Wichmann, Jie Yao, Giuseppe Matullo, Carsten A. Böger, Henry Völzke, Daniela Ruggiero, Federico Murgia, Yoshikuni Kita, Augustine Kong, Giovanni Gambaro, Cinzia Sala, Peter P. Pramstaller, James Scott, Maris Laan, Laura J. Scott, Alistair S. Hall, Sanaz Sedaghat, James F. Wilson, Joanne M. Murabito, Yi-An Ko, Honghuang Lin, Mark Seielstad, Leena Peltonen, Sven Bergmann, Thomas Meitinger, Matthias Nauck, María Soler Artigas, Thomas Illig, Nanette I. Steinle, Samer S. Najjar, Christina Loley, Debbie A Lawlor, Steven C. Hunt, Yali Li, Weihua Zhang, Jie Jin Wang, Daniele Cusi, Marco Orrù, Stephen P. Fortmann, Melissa Garcia, Barry I. Freedman, Joseph M. Lindsay, Juan P. Casas, Tomohiro Katsuya, Grant W. Montgomery, Hubert Scharnagl, Khanh-Dung H. Nguyen, Steven M. Schwartz, Afshin Parsa, Elizabeth G. Holliday, Murielle Bochud, Kiran Musunuru, Bruno H. Stricker, Lori L. Bonnycastle, Ilja M. Nolte, Timothy M. Frayling, Stefan Enroth, Michiel L. Bots, Mark J. Caulfield, Laura Portas, Vincent Chouraki, Carl D. Langefeld, Eran Halperin, Shufeng Chen, Philippa J. Talmud, Terho Lehtimäki, Steve E. Humphries, Gudmar Thorleifsson, Anika Grosshennig, Norbert Watzinger, Fumihiko Takeuchi, Pim van der Harst, Takayoshi Ohkubo, Nabila Bouatia-Naji, Erwin P. Bottinger, Roberto Elosua, Andrew Wong, Vladan Mijatovic, Maija K. Garnaas, Robert Zweiker, Joel N. Hirschhorn, Winfried März, Nilesh J. Samani, Inke R. König, Frank B. Hu, Marcus E. Kleber, Francis S. Collins, Elena Rochtchina, Ewa Zukowska-Szczechowska, Yong Li, Ayse Demirkan, Gina Hilton, G. Ehret, Thomas H. Mosley, Markus Perola, Alexandre F.R. Stewart, Josef Coresh, Olli T. Raitakari, Feng Zhang, Mark Lathrop, Michael Marmot, Yanbin Dong, Christopher J. O'Donnell, Kristin D. Marciante, Asif Rasheed, Mary F. Feitosa, Mary Susan Burnett, Rory Collins, J. Wouter Jukema, Nele Friedrich, Aida Karina Dieffenbach, Ying Wu, Yoon Shin Cho, Aaron Isaacs, Haidong Zhu, Marie Metzger, Myriam Alexander, Tanja B. Grammer, Tatiana Kuznetsova, Dabeeru C. Rao, Jayashri Aragam, Augusto D. Pichard, Jaakko Tuomilehto, Louise V. Wain, Elizabeth J. Atkinson, Tim D. Spector, Reedik Mägi, Tiit Nikopensius, Kenneth M. Kent, Guangju Zhai, Andrew D. Johnson, Menno Pruijm, David P. Strachan, Martin D. Tobin, Joban Sehmi, Janja Nahrstedt, E. Shyong Tai, Thor Aspelund, Jürgen Grässler, Hilma Holm, Matthew Denniff, Joshua W. Knowles, Tien Yin Wong, Erika Salvi, James F. Meschia, Dongfeng Gu, Ron Waksman, Stacey Gabriel, Judith A. Hoffman Bolton, Michael Boehnke, Johannes Haerting, Darina Czamara, Heribert Schunkert, Thomas Quertermous, Peter M. Nilsson, Jong-Young Lee, Yasuharu Tabara, Chittaranjan S. Yajnik, Daniel Levy, John Beilby, Fernando Rivadeneira, Claire Perret, Gudny Eiriksdottir, Jingzhong Ding, George A. Wells, Harold Snieder, Ayo P. Doumatey, Dag S. Thelle, Anja Medack, N. Charlotte Onland-Moret, Michael Stumvoll, David Ellinghaus, Ingrid B. Borecki, Tatsuhiko Tsunoda, Ian H. de Boer, M. Arfan Ikram, Andrew M. Taylor, Johannes H. Smit, Gary F. Mitchell, Anna-Liisa Hartikainen, Markku Laakso, Mark McEvoy, Andrew S. Plump, Toby Johnson, Cornelia M. van Duijn, Ozren Polasek, Wilmar Igl, Vincent Mooser, Rodney J. Scott, Mika Kähönen, Peter Schwarz, Psychiatry, EMGO - Mental health, Pattaro, Cristian, Teumer, Alexander, Gorski, Mathia, Chu, Audrey Y., Li, Man, Mijatovic, Vladan, Garnaas, Maija, Tin, Adrienne, Sorice, Rossella, Li, Yong, Taliun, Daniel, Olden, Matthia, Foster, Meredith, Yang, Qiong, Chen, Ming Huei, Pers, Tune H., Johnson, Andrew D., Ko, Yi An, Fuchsberger, Christian, Tayo, Bamidele, Nalls, Michael, Feitosa, Mary F., Isaacs, Aaron, Dehghan, Abba, D'Adamo, ADAMO PIO, Adeyemo, Adebowale, Dieffenbach, Aida Karina, Zonderman, Alan B., Nolte, Ilja M., Van Der Most, Peter J., Wright, Alan F., Shuldiner, Alan R., Morrison, Alanna C., Hofman, Albert, Smith, Albert V., Dreisbach, Albert W., Franke, Andre, Uitterlinden, Andre G., Metspalu, Andre, Tonjes, Anke, Lupo, Antonio, Robino, Antonietta, Johansson, Åsa, Demirkan, Ayse, Kollerits, Barbara, Freedman, Barry I., Ponte, Belen, Oostra, Ben A., Paulweber, Bernhard, Krämer, Bernhard K., Mitchell, Braxton D., Buckley, Brendan M., Peralta, Carmen A., Hayward, Caroline, Helmer, Catherine, Rotimi, Charles N., Shaffer, Christian M., Müller, Christian, Sala, Cinzia, Van Duijn, Cornelia M., Saint Pierre, Aude, Ackermann, Daniel, Shriner, Daniel, Ruggiero, Daniela, Toniolo, Daniela, Lu, Yingchang, Cusi, Daniele, Czamara, Darina, Ellinghaus, David, Siscovick, David S., Ruderfer, Dougla, Gieger, Christian, Grallert, Harald, Rochtchina, Elena, Atkinson, Elizabeth J., Holliday, Elizabeth G., Boerwinkle, Eric, Salvi, Erika, Bottinger, Erwin P., Murgia, Federico, Rivadeneira, Fernando, Ernst, Florian, Kronenberg, Florian, Hu, Frank B., Navis, Gerjan J., Curhan, Gary C., Ehret, George B., Homuth, Georg, Coassin, Stefan, Thun, Gian Andri, Pistis, Giorgio, Gambaro, Giovanni, Malerba, Giovanni, Montgomery, Grant W., Eiriksdottir, Gudny, Jacobs, Gunnar, Li, Guo, Wichmann, H. Erich, Campbell, Harry, Schmidt, Helena, Wallaschofski, Henri, Völzke, Henry, Brenner, Hermann, Kroemer, Heyo K., Kramer, Holly, Lin, Honghuang, Leach, I. Mateo, Ford, Ian, Guessous, Idri, Rudan, Igor, Prokopenko, Inga, Borecki, Ingrid, Heid, Iris M., Kolcic, Ivana, Persico, Ivana, Jukema, J. Wouter, Wilson, James F., Felix, Janine F., Divers, Jasmin, Lambert, Jean Charle, Stafford, Jeanette M., Gaspoz, Jean Michel, Smith, Jennifer A., Faul, Jessica D., Wang, Jie Jin, Ding, Jingzhong, Hirschhorn, Joel N., Attia, John, Whitfield, John B., Chalmers, John, Viikari, Jorma, Coresh, Josef, Denny, Joshua C., Karjalainen, Juha, Fernandes, Jyotika K., Endlich, Karlhan, Butterbach, Katja, Keene, Keith L., Lohman, Kurt, Portas, Laura, Launer, Lenore J., Lyytikäinen, Leo Pekka, Yengo, Loic, Franke, Lude, Ferrucci, Luigi, Rose, Lynda M., Kedenko, Lyudmyla, Rao, Madhumathi, Struchalin, Maksim, Kleber, Marcus E., Cavalieri, Margherita, Haun, Margot, Cornelis, Marilyn C., Ciullo, Marina, Pirastu, Mario, De Andrade, Mariza, Mcevoy, Mark A., Woodward, Mark, Adam, Martin, Cocca, Massimiliano, Nauck, Matthia, Imboden, Medea, Waldenberger, Melanie, Pruijm, Menno, Metzger, Marie, Stumvoll, Michael, Evans, Michele K., Sale, Michele M., Kähönen, Mika, Boban, Mladen, Bochud, Murielle, Rheinberger, Myriam, Verweij, Niek, Bouatia Naji, Nabila, Martin, Nicholas G., Hastie, Nick, Probst Hensch, Nicole, Soranzo, Nicole, Devuyst, Olivier, Raitakari, Olli, Gottesman, Omri, Franco, Oscar H., Polasek, Ozren, Gasparini, Paolo, Munroe, Patricia B., Ridker, Paul M., Mitchell, Paul, Muntner, Paul, Meisinger, Christa, Smit, Johannes H., Abecasis, Goncalo R., Adair, Linda S., Alexander, Myriam, Altshuler, David, Amin, Najaf, Arking, Dan E., Arora, Pankaj, Aulchenko, Yurii, Bakker, Stephan J. L., Bandinelli, Stefania, Barroso, Ine, Beckmann, Jacques S., Beilby, John P., Bergman, Richard N., Bergmann, Sven, Bis, Joshua C., Boehnke, Michael, Bonnycastle, Lori L., Bornstein, Stefan R., Bots, Michiel L., Bragg Gresham, Jennifer L., Brand, Stefan Martin, Brand, Eva, Braund, Peter S., Brown, Morris J., Burton, Paul R., Casas, Juan P., Caulfield, Mark J., Chakravarti, Aravinda, Chambers, John C., Chandak, Giriraj R., Chang, Yen Pei C., Charchar, Fadi J., Chaturvedi, Nish, Cho, Yoon Shin, Clarke, Robert, Collins, Francis S., Collins, Rory, Connell, John M., Cooper, Jackie A., Cooper, Matthew N., Cooper, Richard S., Corsi, Anna Maria, Dörr, Marcu, Dahgam, Santosh, Danesh, John, Smith, George Davey, Day, Ian N. M., Deloukas, Pano, Denniff, Matthew, Dominiczak, Anna F., Dong, Yanbin, Doumatey, Ayo, Elliott, Paul, Elosua, Roberto, Erdmann, Jeanette, Eyheramendy, Susana, Farrall, Martin, Fava, Cristiano, Forrester, Terrence, Fowkes, F. Gerald R., Fox, Ervin R., Frayling, Timothy M., Galan, Pilar, Ganesh, Santhi K., Garcia, Melissa, Gaunt, Tom R., Glazer, Nicole L., Go, Min Jin, Goel, Anuj, Grässler, Jürgen, Grobbee, Diederick E., Groop, Leif, Guarrera, Simonetta, Guo, Xiuqing, Hadley, David, Hamsten, Ander, Han, Bok Ghee, Hardy, Rebecca, Hartikainen, Anna Liisa, Heath, Simon, Heckbert, Susan R., Hedblad, Bo, Hercberg, Serge, Hernandez, Dena, Hicks, Andrew A., Hilton, Gina, Hingorani, Aroon D., Hoffman Bolton, Judith A., Hopewell, Jemma C., Howard, Philip, Humphries, Steve E., Hunt, Steven C., Hveem, Kristian, Ikram, M. Arfan, Islam, Muhammad, Iwai, Naoharu, Jarvelin, Marjo Riitta, Jackson, Anne U., Jafar, Tazeen H., Janipalli, Charles S., Johnson, Toby, Kathiresan, Sekar, Khaw, Kay Tee, Kim, Hyung Lae, Kinra, Sanjay, Kita, Yoshikuni, Kivimaki, Mika, Kooner, Jaspal S., Kumar, M. J. Kranthi, Kuh, Diana, Kulkarni, Smita R., Kumari, Meena, Kuusisto, Johanna, Kuznetsova, Tatiana, Laakso, Markku, Laan, Mari, Laitinen, Jaana, Lakatta, Edward G., Langefeld, Carl D., Larson, Martin G., Lathrop, Mark, Lawlor, Debbie A., Lawrence, Robert W., Lee, Jong Young, Lee, Nanette R., Levy, Daniel, Li, Yali, Longstreth, Will T., Luan, Jian'An, Lucas, Gavin, Ludwig, Barbara, Mangino, Massimo, Mani, K. Radha, Marmot, Michael G., Mattace Raso, Francesco U. S., Matullo, Giuseppe, Mcardle, Wendy L., Mckenzie, Colin A., Meitinger, Thoma, Melander, Olle, Meneton, Pierre, Meschia, James F., Miki, Tetsuro, Milaneschi, Yuri, Mohlke, Karen L., Mooser, Vincent, Morken, Mario A., Morris, Richard W., Mosley, Thomas H., Najjar, Samer, Narisu, Narisu, Newton Cheh, Christopher, Nguyen, Khanh Dung Hoang, Nilsson, Peter, Nyberg, Fredrik, O'Donnell, Christopher J., Ogihara, Toshio, Ohkubo, Takayoshi, Okamura, Tomonori, Ong, Rick Twee Hee, Ongen, Halit, Onland Moret, N. Charlotte, O'Reilly, Paul F., Org, Elin, Orru, Marco, Palmas, Walter, Palmen, Jutta, Palmer, Lyle J., Palmer, Nicholette D., Parker, Alex N., Peden, John F., Peltonen, Leena, Perola, Marku, Pihur, Vasyl, Platou, Carl G. P., Plump, Andrew, Prabhakaran, Dorairajan, Psaty, Bruce M., Raffel, Leslie J., Rao, Dabeeru C., Rasheed, Asif, Ricceri, Fulvio, Rice, Kenneth M., Rosengren, Annika, Rotter, Jerome I., Rudock, Megan E., Sõber, Siim, Salako, Tunde, Saleheen, Danish, Salomaa, Veikko, Samani, Nilesh J., Schwartz, Steven M., Schwarz, Peter E. H., Scott, Laura J., Scott, Jame, Scuteri, Angelo, Sehmi, Joban S., Seielstad, Mark, Seshadri, Sudha, Sharma, Pankaj, Shaw Hawkins, Sue, Shi, Gang, Shrine, Nick R. G., Sijbrands, Eric J. G., Sim, Xueling, Singleton, Andrew, Sjögren, Marketa, Smith, Nicholas L., Artigas, Maria Soler, Spector, Tim D., Staessen, Jan A., Stancakova, Alena, Steinle, Nanette I., Strachan, David P., Stringham, Heather M., Sun, Yan V., Swift, Amy J., Tabara, Yasuharu, Tai, E. Shyong, Talmud, Philippa J., Taylor, Andrew, Terzic, Jano, Thelle, Dag S., Tobin, Martin D., Tomaszewski, Maciej, Tripathy, Vikal, Tuomilehto, Jaakko, Tzoulaki, Ioanna, Uda, Manuela, Ueshima, Hirotsugu, Uiterwaal, Cuno S. P. M., Umemura, Satoshi, Van Der Harst, Pim, Van Der Schouw, Yvonne T., Van Gilst, Wiek H., Vartiainen, Erkki, Vasan, Ramachandran S., Veldre, Gudrun, Verwoert, Germaine C., Viigimaa, Margu, Vinay, D. G., Vineis, Paolo, Voight, Benjamin F., Vollenweider, Peter, Wagenknecht, Lynne E., Wain, Louise V., Wang, Xiaoling, Wang, Thomas J., Wareham, Nicholas J., Watkins, Hugh, Weder, Alan B., Whincup, Peter H., Wiggins, Kerri L., Witteman, Jacqueline C. M., Wong, Andrew, Wu, Ying, Yajnik, Chittaranjan S., Yao, Jie, Young, J. H., Zelenika, Diana, Zhai, Guangju, Zhang, Weihua, Zhang, Feng, Zhao, Jing Hua, Zhu, Haidong, Zhu, Xiaofeng, Zitting, Paavo, Zukowska Szczechowska, Ewa, Okada, Yukinori, Wu, Jer Yuarn, Gu, Dongfeng, Takeuchi, Fumihiko, Takahashi, Atsushi, Maeda, Shiro, Tsunoda, Tatsuhiko, Chen, Peng, Lim, Su Chi, Wong, Tien Yin, Liu, Jianjun, Young, Terri L., Aung, Tin, Teo, Yik Ying, Kim, Young Jin, Kang, Daehee, Chen, Chien Hsiun, Tsai, Fuu Jen, Chang, Li Ching, Fann, S. J. Cathy, Mei, Hao, Hixson, James E., Chen, Shufeng, Katsuya, Tomohiro, Isono, Masato, Albrecht, Eva, Yamamoto, Kazuhiko, Kubo, Michiaki, Nakamura, Yusuke, Kamatani, Naoyuki, Kato, Norihiro, He, Jiang, Chen, Yuan Tsong, Tanaka, Toshihiro, Reilly, Muredach P., Schunkert, Heribert, Assimes, Themistocles L., Hall, Alistair, Hengstenberg, Christian, König, Inke R., Laaksonen, Reijo, Mcpherson, Ruth, Thompson, John R., Thorsteinsdottir, Unnur, Ziegler, Andrea, Absher, Devin, Chen, Li, Cupples, L. Adrienne, Halperin, Eran, Li, Mingyao, Musunuru, Kiran, Preuss, Michael, Schillert, Arne, Thorleifsson, Gudmar, Wells, George A., Holm, Hilma, Roberts, Robert, Stewart, Alexandre F. R., Fortmann, Stephen, Go, Alan, Hlatky, Mark, Iribarren, Carlo, Knowles, Joshua, Myers, Richard, Quertermous, Thoma, Sidney, Steven, Risch, Neil, Tang, Hua, Blankenberg, Stefan, Schnabel, Renate, Sinning, Christoph, Lackner, Karl J., Tiret, Laurence, Nicaud, Viviane, Cambien, Francoi, Bickel, Christoph, Rupprecht, Hans J., Perret, Claire, Proust, Carole, Münzel, Thomas F., Barbalic, Maja, Chen, Ida Yii Der, Demissie Banjaw, Serkalem, Folsom, Aaron, Lumley, Thoma, Marciante, Kristin, Taylor, Kent D., Volcik, Kelly, Gretarsdottir, Solveig, Gulcher, Jeffrey R., Kong, Augustine, Stefansson, Kari, Thorgeirsson, Gudmundur, Andersen, Karl, Fischer, Marcu, Grosshennig, Anika, Linsel Nitschke, Patrick, Stark, Klau, Schreiber, Stefan, Aherrahrou, Zouhair, Bruse, Petra, Doering, Angela, Klopp, Norman, Diemert, Patrick, Loley, Christina, Medack, Anja, Nahrstedt, Janja, Peters, Annette, Wagner, Arnika K., Willenborg, Christina, Böhm, Bernhard O., Dobnig, Harald, Grammer, Tanja B., Hoffmann, Michael M., Meinitzer, Andrea, Winkelmann, Bernhard R., Pilz, Stefan, Renner, Wilfried, Scharnagl, Hubert, Stojakovic, Tatjana, Tomaschitz, Andrea, Winkler, Karl, Guiducci, Candace, Burtt, Noel, Gabriel, Stacey B., Dandona, Sonny, Jarinova, Olga, Qu, Liming, Wilensky, Robert, Matthai, William, Hakonarson, Hakon H., Devaney, Joe, Burnett, Mary Susan, Pichard, Augusto D., Kent, Kenneth M., Satler, Lowell, Lindsay, Joseph M., Waksman, Ron, Knouff, Christopher W., Waterworth, Dawn M., Walker, Max C., Epstein, Stephen E., Rader, Daniel J., Nelson, Christopher P., Wright, Benjamin J., Balmforth, Anthony J., Ball, Stephen G., Loehr, Laura R., Rosamond, Wayne D., Benjamin, Emelia, Haritunians, Talin, Couper, David, Murabito, Joanne, Wang, Ying A., Stricker, Bruno H., Chang, Patricia P., Willerson, James T., Felix, Stephan B., Watzinger, Norbert, Aragam, Jayashri, Zweiker, Robert, Lind, Lar, Rodeheffer, Richard J., Greiser, Karin Halina, Deckers, Jaap W., Stritzke, Jan, Ingelsson, Erik, Kullo, Iftikhar, Haerting, Johanne, Reffelmann, Thorsten, Redfield, Margaret M., Werdan, Karl, Mitchell, Gary F., Arnett, Donna K., Gottdiener, John S., Blettner, Maria, Friedrich, Nele, Kovacs, Peter, Wild, Philipp S., Froguel, Philippe, Rettig, Rainer, Mägi, Reedik, Biffar, Reiner, Schmidt, Reinhold, Middelberg, Rita P. S., Carroll, Robert J., Penninx, Brenda W., Scott, Rodney J., Katz, Ronit, Sedaghat, Sanaz, Wild, Sarah H., Kardia, Sharon L. R., Ulivi, Sheila, Hwang, Shih Jen, Enroth, Stefan, Kloiber, Stefan, Trompet, Stella, Stengel, Benedicte, Hancock, Stephen J., Turner, Stephen T., Rosas, Sylvia E., Stracke, Sylvia, Harris, Tamara B., Zeller, Tanja, Zemunik, Tatijana, Lehtimäki, Terho, Illig, Thoma, Aspelund, Thor, Nikopensius, Tiit, Esko, Tonu, Tanaka, Toshiko, Gyllensten, Ulf, Völker, Uwe, Emilsson, Valur, Vitart, Veronique, Aalto, Ville, Gudnason, Vilmundur, Chouraki, Vincent, Chen, Wei Min, Igl, Wilmar, März, Winfried, Koenig, Wolfgang, Lieb, Wolfgang, Loos, Ruth J. F., Liu, Yongmei, Snieder, Harold, Pramstaller, Peter P., Parsa, Afshin, O'Connell, Jeffrey R., Susztak, Katalin, Hamet, Pavel, Tremblay, Johanne, De Boer, Ian H., Böger, Carsten A., Goessling, Wolfram, Chasman, Daniel I., Köttgen, Anna, Kao, W. H. Linda, Fox, Caroline S., RS: CARIM - R1.06 - Genetic Epidemiology and Genomics of cardiovascular diseases, Biochemie, RS: FHML MaCSBio, Ehret, Georg Benedikt, Guessous, Idris, Gaspoz, Jean-Michel, Life Course Epidemiology (LCE), Lifestyle Medicine (LM), Groningen Kidney Center (GKC), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Polymer Chemistry and Bioengineering, Value, Affordability and Sustainability (VALUE), Stem Cell Aging Leukemia and Lymphoma (SALL), Epidemiology, Public Health, Internal Medicine, Clinical Genetics, Erasmus MC other, Genetic Identification, ICBP Consortium, AGEN Consortium, CHARGe-Heart Failure Group, ECHOGen Consortium, CARDIOGRAM, Abecasis, GR., Adair, LS., Alexander, M., Altshuler, D., Amin, N., Arking, DE., Arora, P., Aulchenko, Y., Bakker, SJ., Bandinelli, S., Barroso, I., Beckmann, JS., Beilby, JP., Bergman, RN., Bergmann, S., Bis, JC., Boehnke, M., Bonnycastle, LL., Bornstein, SR., Bots, ML., Bragg-Gresham, JL., Brand, SM., Brand, E., Braund, PS., Brown, MJ., Burton, PR., Casas, JP., Caulfield, MJ., Chakravarti, A., Chambers, JC., Chandak, GR., Chang, YP., Charchar, FJ., Chaturvedi, N., Shin Cho, Y., Clarke, R., Collins, FS., Collins, R., Connell, JM., Cooper, JA., Cooper, MN., Cooper, RS., Corsi, AM., Dörr, M., Dahgam, S., Danesh, J., Davey Smith, G., Day, IN., Deloukas, P., Denniff, M., Dominiczak, AF., Dong, Y., Doumatey, A., Elliott, P., Elosua, R., Erdmann, J., Eyheramendy, S., Farrall, M., Fava, C., Forrester, T., Fowkes, FG., Fox, ER., Frayling, TM., Galan, P., Ganesh, SK., Garcia, M., Gaunt, TR., Glazer, NL., Go, MJ., Goel, A., Grässler, J., Grobbee, DE., Groop, L., Guarrera, S., Guo, X., Hadley, D., Hamsten, A., Han, BG., Hardy, R., Hartikainen, AL., Heath, S., Heckbert, SR., Hedblad, B., Hercberg, S., Hernandez, D., Hicks, AA., Hilton, G., Hingorani, AD., Bolton, JA., Hopewell, JC., Howard, P., Humphries, SE., Hunt, SC., Hveem, K., Ikram, MA., Islam, M., Iwai, N., Jarvelin, MR., Jackson, AU., Jafar, TH., Janipalli, CS., Johnson, T., Kathiresan, S., Khaw, KT., Kim, HL., Kinra, S., Kita, Y., Kivimaki, M., Kooner, JS., Kumar, MJ., Kuh, D., Kulkarni, SR., Kumari, M., Kuusisto, J., Kuznetsova, T., Laakso, M., Laan, M., Laitinen, J., Lakatta, EG., Langefeld, CD., Larson, MG., Lathrop, M., Lawlor, DA., Lawrence, RW., Lee, JY., Lee, NR., Levy, D., Li, Y., Longstreth, WT., Luan£££Jian'an£££ J., Lucas, G., Ludwig, B., Mangino, M., Mani, KR., Marmot, MG., Mattace-Raso, FU., Matullo, G., McArdle, WL., McKenzie, CA., Meitinger, T., Melander, O., Meneton, P., Meschia, JF., Miki, T., Milaneschi, Y., Mohlke, KL., Mooser, V., Morken, MA., Morris, RW., Mosley, TH., Najjar, S., Narisu, N., Newton-Cheh, C., Nguyen, KD., Nilsson, P., Nyberg, F., O'Donnell, CJ., Ogihara, T., Ohkubo, T., Okamura, T., Ong, RT., Ongen, H., Onland-Moret, NC., O'Reilly, PF., Org, E., Orru, M., Palmas, W., Palmen, J., Palmer, LJ., Palmer, ND., Parker, AN., Peden, JF., Peltonen, L., Perola, M., Pihur, V., Platou, CG., Plump, A., Prabhakaran, D., Psaty, BM., Raffel, LJ., Rao, DC., Rasheed, A., Ricceri, F., Rice, KM., Rosengren, A., Rotter, JI., Rudock, ME., Sõber, S., Salako, T., Saleheen, D., Salomaa, V., Samani, NJ., Schwartz, SM., Schwarz, PE., Scott, LJ., Scott, J., Scuteri, A., Sehmi, JS., Seielstad, M., Seshadri, S., Sharma, P., Shaw-Hawkins, S., Shi, G., Shrine, NR., Sijbrands, EJ., Sim, X., Singleton, A., Sjögren, M., Smith, NL., Soler Artigas, M., Spector, TD., Staessen, JA., Stancakova, A., Steinle, NI., Strachan, DP., Stringham, HM., Sun, YV., Swift, AJ., Tabara, Y., Tai, ES., Talmud, PJ., Taylor, A., Terzic, J., Thelle, DS., Tobin, MD., Tomaszewski, M., Tripathy, V., Tuomilehto, J., Tzoulaki, I., Uda, M., Ueshima, H., Uiterwaal, CS., Umemura, S., van der Harst, P., van der Schouw YT., van Gilst WH., Vartiainen, E., Vasan, RS., Veldre, G., Verwoert, GC., Viigimaa, M., Vinay, DG., Vineis, P., Voight, BF., Vollenweider, P., Wagenknecht, LE., Wain, LV., Wang, X., Wang, TJ., Wareham, NJ., Watkins, H., Weder, AB., Whincup, PH., Wiggins, KL., Witteman, JC., Wong, A., Wu, Y., Yajnik, CS., Yao, J., Young, JH., Zelenika, D., Zhai, G., Zhang, W., Zhang, F., Zhao, JH., Zhu, H., Zhu, X., Zitting, P., Zukowska-Szczechowska, E., Okada, Y., Wu, JY., Gu, D., Takeuchi, F., Takahashi, A., Maeda, S., Tsunoda, T., Chen, P., Lim, SC., Wong, TY., Liu, J., Young, TL., Aung, T., Teo, YY., Kim, YJ., Kang, D., Chen, CH., Tsai, FJ., Chang, LC., Fann, SJ., Mei, H., Hixson, JE., Chen, S., Katsuya, T., Isono, M., Albrecht, E., Yamamoto, K., Kubo, M., Nakamura, Y., Kamatani, N., Kato, N., He, J., Chen, YT., Tanaka, T., Reilly, MP., Schunkert, H., Assimes, TL., Hall, A., Hengstenberg, C., König, IR., Laaksonen, R., McPherson, R., Thompson, JR., Thorsteinsdottir, U., Ziegler, A., Absher, D., Chen, L., Cupples, LA., Halperin, E., Li, M., Musunuru, K., Preuss, M., Schillert, A., Thorleifsson, G., Wells, GA., Holm, H., Roberts, R., Stewart, AF., Fortmann, S., Go, A., Hlatky, M., Iribarren, C., Knowles, J., Myers, R., Quertermous, T., Sidney, S., Risch, N., Tang, H., Blankenberg, S., Schnabel, R., Sinning, C., Lackner, KJ., Tiret, L., Nicaud, V., Cambien, F., Bickel, C., Rupprecht, HJ., Perret, C., Proust, C., Münzel, TF., Barbalic, M., Chen, IY., Demissie-Banjaw, S., Folsom, A., Lumley, T., Marciante, K., Taylor, KD., Volcik, K., Gretarsdottir, S., Gulcher, JR., Kong, A., Stefansson, K., Thorgeirsson, G., Andersen, K., Fischer, M., Grosshennig, A., Linsel-Nitschke, P., Stark, K., Schreiber, S., Aherrahrou, Z., Bruse, P., Doering, A., Klopp, N., Diemert, P., Loley, C., Medack, A., Nahrstedt, J., Peters, A., Wagner, AK., Willenborg, C., Böhm, BO., Dobnig, H., Grammer, TB., Hoffmann, MM., Meinitzer, A., Winkelmann, BR., Pilz, S., Renner, W., Scharnagl, H., Stojakovic, T., Tomaschitz, A., Winkler, K., Guiducci, C., Burtt, N., Gabriel, SB., Dandona, S., Jarinova, O., Qu, L., Wilensky, R., Matthai, W., Hakonarson, HH., Devaney, J., Burnett, MS., Pichard, AD., Kent, KM., Satler, L., Lindsay, JM., Waksman, R., Knouff, CW., Waterworth, DM., Walker, MC., Epstein, SE., Rader, DJ., Nelson, CP., Wright, BJ., Balmforth, AJ., Ball, SG., Loehr, LR., Rosamond, WD., Benjamin, E., Haritunians, T., Couper, D., Murabito, J., Wang, YA., Stricker, BH., Chang, PP., Willerson, JT., Felix, SB., Watzinger, N., Aragam, J., Zweiker, R., Lind, L., Rodeheffer, RJ., Greiser, KH., Deckers, JW., Stritzke, J., Ingelsson, E., Kullo, I., Haerting, J., Reffelmann, T., Redfield, MM., Werdan, K., Mitchell, GF., Arnett, DK., Gottdiener, JS., Blettner, M., and Friedrich, N.
Subjects: 0301 basic medicine, Nephrology, Genetics and Molecular Biology (all), estimated glomerular filtration rate, estimated glomerular filtration rate, chronic kidney disease, genetic determinants, General Physics and Astronomy, Kidney development, Genome-wide association study, Biochemistry, Settore MED/14 - NEFROLOGIA, Renal Insufficiency, Chronic, Genetics, AGEN Consortium, ddc:616, education.field_of_study, Kidney, Stage renal-disease, Multidisciplinary, Genome-wide association, CHARGe-Heart Failure Group, Gene Expression Regulation, Genome-Wide Association Study, Genotype, Humans, Renal Insufficiency, Chronic, Genetic Predisposition to Disease, Biochemistry, Genetics and Molecular Biology (all), Chemistry (all), Physics and Astronomy (all), Metaanalysis, Renal Insufficiency, Chronic/genetics, Biological sciences, Serum creatinine, medicine.anatomical_structure, Efficient, Ronyons -- Fisiologia, Hypertension, ICBP Consortium, Transmembrane transporter activity, genetic association, loci, kidney function, CARDIOGRAM, Human, medicine.medical_specialty, Science, Population, Renal function, ECHOGen Consortium, Replication, Biology, Environment, Research Support, General Biochemistry, Genetics and Molecular Biology, N.I.H, genetic determinants, 03 medical and health sciences, GENOME-WIDE ASSOCIATION, FALSE DISCOVERY RATES, STAGE RENAL-DISEASE, SERUM CREATININE, METAANALYSIS, VARIANTS, INDIVIDUALS, POPULATION, RISK, HYPERTENSION, Kidney function, Research Support, N.I.H., Extramural, Internal medicine, MD Multidisciplinary, medicine, Journal Article, eGFRcrea, eGFRcys, ddc:610, Genetik, Mortality, education, ddc:613, urogenital system, Individuals, Extramural, General Chemistry, ta3121, medicine.disease, R1, 030104 developmental biology, 570 Life sciences, biology, Genètica, chronic kidney disease, Kidney disease, Meta-Analysis
Abstract: Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways. J.T. and P.H. are consultants for Servier. J.C. received research grants and honoraria from Servier. K.S. obtained research support from Boehringer Ingelheim. The remaining authors declared no competing financial interests.
Published: 2016

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33 results on '"Felix, Stephan B"'

1. Left ventricular hypertrophy as a risk factor for accelerated brain aging: Results from the Study of Health in Pomerania.

2. The Correlation of Lung Function Parameters, Blood Pressure and Beta-Blocker Medication in a General Population.

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

4. [Blood pressure measurement in the NAKO German National Cohort (GNC) - differences in methods, distribution of blood pressure values, and awareness of hypertension compared to other population-based studies in Germany].

5. Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries.

6. Transcriptome-Wide Analysis Identifies Novel Associations With Blood Pressure.

7. Genetic Interactions with Age, Sex, Body Mass Index, and Hypertension in Relation to Atrial Fibrillation: The AFGen Consortium.

8. Hypertension in Germany.

9. Assessing cutoff values for increased exercise blood pressure to predict incident hypertension in a general population.

10. A meta-analysis of gene expression signatures of blood pressure and hypertension.

11. A new, accurate predictive model for incident hypertension.

12. Molecular changes in the early phase of renin-dependent cardiac hypertrophy in hypertensive cyp1a1ren-2 transgenic rats.

13. Quinaprilat: a review of its pharmacokinetics, pharmacodynamics, toxicological data and clinical application.

14. The association between subclinical hyperthyroidism and blood pressure in a population-based study.

15. Gender differences in the relation between number of teeth and systolic blood pressure.

16. Endothelial nitric oxide synthase Glu298Asp gene polymorphism, blood pressure and hypertension in a general population sample.

17. Meta-analysis identifies common and rare variants influencing blood pressure and overlapping with metabolic trait loci

18. The Association of Serum Testosterone Levels and Ventricular Repolarization

19. Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure

20. Hypertension in Germany: Data From Seven Population-Based Epidemiological Studies (1994–2012)

21. Subclinical hyperthyroidism and blood pressure in a populationbased prospective cohort study.

22. Prevalence and association analysis of obstructive sleep apnea with gender and age differences – Results of SHIP‐Trend.

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

24. A meta-analysis of gene expression signatures of blood pressure and hypertension

25. Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries

26. Riociguat for Patients With Pulmonary Hypertension Caused by Systolic Left Ventricular Dysfunction A Phase lib Double-Blind, Randomized, Placebo-Controlled, Dose-Ranging Hemodynamic Study.

27. Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-representative studies with 104 million participants

28. Low serum magnesium concentrations predict cardiovascular and all-cause mortality

29. Association between glycosylated haemoglobin A1c and endothelial function in an adult non-diabetic population

30. Low serum magnesium concentrations predict increase in left ventricular mass over 5 years independently of common cardiovascular risk factors

31. Urinary albumin excretion, even within the normal range, predicts an increase in left ventricular mass over the following 5 years.

32. Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries

33. Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function

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