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13. Temporal changes in secondary prevention and cardiovascular outcomes after revascularization for peripheral arterial disease in Denmark

Author

Trinder, M., Wang, Y.A., Madsen, C.M., Ponomarev, T., Bohunek, L., Daisely, B.A., Kong, H.J., Blauw, L.L., Nordestgaard, B.G., Tybjaerg-Hansen, A., Wurfel, M.M., Russell, J.A., Walley, K.R., Rensen, P.C.N., Boyd, J.H., and Brunham, L.R.

Subjects
peripheral arterial disease, incidence, epidemiology, prognosis, cardiovascular diseases
Abstract

Background:Patients with peripheral arterial disease (PAD) are at increased risk of cardiovascular morbidity and mortality. Medical prevention with antithrombotic and statin therapies is a mainstay of treatment to prevent adverse outcomes; nevertheless, patients with PAD are often undertreated. This study describes the temporal changes in medical prevention and adverse outcomes in a national cohort of patients with symptomatic PAD after revascularization.Methods:We identified all patients with a first open surgical or endovascular revascularization procedure in the lower extremities or abdomen in Denmark, from 2000 to 2016. We examined temporal changes in the use of aspirin, clopidogrel, and statins and 1-year cause-specific hazard ratios for adverse clinical outcomes, after adjusting for procedure type, treatment indication, age, sex, and cardiovascular risk factors. The analyses were performed overall and within strata of index procedure (endovascular versus surgical), treatment indication, age, sex, and high-risk comorbidities.Results:Between 2000 and 2016, we identified 32 911 patients who underwent revascularization for symptomatic PAD. The mean age was 69 years and increased over time, as did the burden of comorbidity. The cumulative incidence of medication use increased between 2000 to 2004 and 2013 to 2016, respectively, from 57.3% to 64.3% for aspirin, 3.6% to 24.8% for clopidogrel, and 36.2% to 77.1% for statins. Concurrently, the 1-year outcome rates declined. Compared with 2000 to 2004, the adjusted hazard ratios in 2013 to 2016 were 0.73 (95% CI, 0.62-0.84) for major adverse cardiovascular events, 0.92 (95% CI, 0.85-1.00) for major adverse limb events, 0.60 (95% CI, 0.48-0.74) for myocardial infarction, 0.94 (95% CI, 0.75-1.18) for ischemic stroke, 0.92 (95% CI, 0.75-1.12) for major bleeding, 0.54 (95% CI, 0.39-0.76) for cardiovascular death, and 0.80 (95% CI, 0.72-0.88) for all-cause death. These improvements in prognosis were most prominent from 2000 to 2004 to 2005 to 2008 and occurred in all strata of index procedure, treatment indication, sex, age, and comorbidity. In contrast, the adjusted hazard ratio for major amputations was 1.00 (95% CI, 0.90-1.11) when comparing 2013 to 2016 to 2000 to 2004.Conclusions:Medical prevention of adverse events has increased considerably over time in patients who underwent revascularization for symptomatic PAD. This increase was accompanied by reductions in all adverse outcomes, except major amputations.

Published
2021

18. SMPD scenarios of spatial distribution of human population in China

Author

Yue, T.X., Wang, Y.A., Liu, J.Y., Chen, S.P., Tian, Y.Z., and Su, B.P.

Subjects
Environmental issues, Social sciences, Sociology and social work
Abstract

Three scenarios of spatial distribution of human population in China are developed in the years 2010 and 2020, respectively by means of the method of surface modeling of population distribution (SMPD). Each one of the SMPD scenarios is defined as a plausible alternative future under particular assumptions of elevation, water system, net primary productivity (NPP), urbanization, transport infrastructure development, and population growth. The SMPD scenarios show that if population could freely migrate within the whole China, the balanced ratios of population in the western region, the middle region and the eastern region to total population in the whole China would be 16%, 33% and 52%, respectively. KEY WORDS: Spatial distribution; surface modeling; scenarios; GIS.

Published
2005

20. Numerical simulation of population distribution in China

Author

Yue, T.X., Wang, Y.A., Chen, S.P., Liu, J.Y., Qiu, D.S., Deng, X.Z., Liu, M.L., and Tian, Y.Z.

Subjects
Population geography -- Models, Environmental issues, Social sciences, Sociology and social work
Abstract

A model for simulating population distribution (MSPD) of China is developed based on the grid generation method and the Control of MapObjects of geographical information system. Elevation, net primary productivity, land use and land cover, city sizes and their spatial distribution, and spatial distribution of transport infrastructures are taken into full account in the MSPD. The result from the MSPD shows that in 2000, 90.8% of the total population of China distributed on the southeastern side of the Heihe-Tengchong line. The ratio of population on the northwestern side to total population of China has been increasing since 1935. The yearly growth rate was 0.8% from 1935 to 1990 and 6.1% from 1990 to 2000. One important advantage of the MSPD is that when scenarios of land cover, spatial distributions of transport infrastructures and cities are available, scenarios of spatial population distribution can be developed on the basis of total population forecast. KEY WORDS: population distribution; numerical simulation; grid generation; geographical information system.

Published
2003

25. 465P Single nucleotide polymorphism (SNP) analysis identifies potential prognostic and predictive biomarker in patients (pts) with metastatic colorectal cancer (mCRC) treated with regorafenib in the phase III CORRECT trial

Author

Battaglin, F., primary, Zhang, W., additional, Skubala, A., additional, Arai, H., additional, Wang, J., additional, Soni, S., additional, Wang, Y.A., additional, Köchert, K., additional, Schulz, A., additional, Teufel, M., additional, Millstein, J., additional, and Lenz, H.J., additional

Published
2020
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30. Prediction of outcomes of extremely low gestational age newborns in Australia and New Zealand.

Author

Yeo K.T., Wang Y.A., Le Marsney R., Schindler T., Bolisetty S., Haslam R., Lui K., Marshall P., Schmidt P., Craven P., De Waal K., Simmer K., Gill A., Pillow J., Stack J., Cooke L., Casalaz D., Holberton J., Barfield C., Downe L., Singde V., Stewart M., Berry A., Carmo K.B., Darlow B., Broadbent R., Mildenhall L., Buksh M., Bourchier D., Carpenter L., Richardson V., Chambers G., Buckmaster A., Rajadurai V.S., Bajuk B., Safi N., Hunt R., Kilburn C., De Paoli T., Paradisis M., Rieger I., Lutz T., Reid S., Cartwright D., Koorts P., Kuschel C., Doyle L., Numa A., Carlisle H., Badawi N., Koh G., Resnick S., Luig M., Andersen C., Lyn A., Yeo K.T., Wang Y.A., Le Marsney R., Schindler T., Bolisetty S., Haslam R., Lui K., Marshall P., Schmidt P., Craven P., De Waal K., Simmer K., Gill A., Pillow J., Stack J., Cooke L., Casalaz D., Holberton J., Barfield C., Downe L., Singde V., Stewart M., Berry A., Carmo K.B., Darlow B., Broadbent R., Mildenhall L., Buksh M., Bourchier D., Carpenter L., Richardson V., Chambers G., Buckmaster A., Rajadurai V.S., Bajuk B., Safi N., Hunt R., Kilburn C., De Paoli T., Paradisis M., Rieger I., Lutz T., Reid S., Cartwright D., Koorts P., Kuschel C., Doyle L., Numa A., Carlisle H., Badawi N., Koh G., Resnick S., Luig M., Andersen C., and Lyn A.

Abstract

Objective To determine the accuracy of the National Institute of Child Health and Human Development (NICHD) calculator in predicting death and neurodevelopmental impairment in Australian and New Zealand infants. Design Population-based cohort study. setting Australia and New Zealand. Patients Preterm infants 22-25 completed weeks gestation. Interventions Comparison of NICHD calculator predicted rates of death and death or neurodevelopmental impairment, with actual rates recorded in the Australian and New Zealand Neonatal Network cohort. Main outcome measures Infant death and death or neurodevelopmental impairment rates. results A total of 714 infants were included in the study. Of these infants, 100 (14.0%) were <24 weeks, 389 (54.5%) male, 529 (74.1%) were singletons, 42 (5.9%) had intrauterine growth restriction, 563 (78.9%) received antenatal steroids and 625 (87.5 %) were born in a tertiary hospital. There were 288 deaths (40.3%), 75 infants (10.5%) with neurodevelopment impairment and 363 (50.8%) with death or neurodevelopmental impairment. The area under the curve (AUC) for prediction of death and the composite death or neurodevelopmental impairment by the NICHD calculator in our population was 0.65(95% CI 0.61 to 0.69) and 0.65 (95% CI 0.61 to 0.69), respectively. When stratified and compared with gestational age outcomes, the AUC did not change substantially for the outcomes investigated. The calculator was less accurate with outcome predictions at the extreme categories of predicted outcomes-underestimation of outcomes for those predicted to have the lowest risk (<20%) and overestimation for those in the highest risk category (>>80%). conclusion In our recent cohort of extremely preterm infants, the NICHD model does not accurately predict outcomes and is marginally better than gestational age based outcomes.Copyright © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved.

Published
2018

31. Comparing very low birth weight versus very low gestation cohort methods for outcome analysis of high risk preterm infants.

Author

Austin N., Andersen C., Darlow B., Broadbent R., Corban J., Mildenhall L., Battin M., Bourchier D., Richardson V., Haslam R., Rajadurai V.S., Kajetanowicz A., Synnes A., Rouvinez-Bouali N., Piedboeuf B., Bertelle V., Bulleid B., Yee W., Shivananda S., Lee K.-S., Seshia M., Barrington K., Lefebvre F., McMillan D., Andrews W., Kovacs L., Dow K., da Silva O., Riley P., Peliowski A., Aziz K., Cieslak Z., Kalapesi Z., Sankaran K., Faucher D., Alvaro R., Canning R., Ojah C., Monterrosa L., Dunn M., Sorokan T., Harrison A., Nwaesei C., Adie M., Hakansson S., Segerdahl N., Morad T., Moren S., Stenberg A., Simonsson C., Stigsson L., Christensen J.L., Amasn L., Ingemanson F., osterdal L., Ellstrom K.-G., Abrahamsson T., Heimdahl I., Hagg T., Hedlund A., Lund E.E., Westrup B., Sarman I., Jobe A.S., Fredsriksson M., Palm A., Malmstrom B., Lindberg E., Ljungdahl O., Eriksson K., Koller-Smith L.I.M., Shah P., Ye X.Y., Sjors G., Wang Y.A., Chow S.S.W., Darlow B.A., Lee S.K., Hakanson S., Lui K., Marshall P., Craven P., Simmer K., Stack J., Knight D., Watkins A., Ramsden A., Tan K., Bawden K., Downe L., Singde V., Stewart M., Berry A., Hunt R., Kilburn C., Dargaville P., Paradisis M., Evans N., Reid S., Cartwright D., Kuschel C., Doyle L., Numa A., Kecskes Z., Badawi N., Koh G., Resnick S., Tracy M., Tarnow-Mordi W., Austin N., Andersen C., Darlow B., Broadbent R., Corban J., Mildenhall L., Battin M., Bourchier D., Richardson V., Haslam R., Rajadurai V.S., Kajetanowicz A., Synnes A., Rouvinez-Bouali N., Piedboeuf B., Bertelle V., Bulleid B., Yee W., Shivananda S., Lee K.-S., Seshia M., Barrington K., Lefebvre F., McMillan D., Andrews W., Kovacs L., Dow K., da Silva O., Riley P., Peliowski A., Aziz K., Cieslak Z., Kalapesi Z., Sankaran K., Faucher D., Alvaro R., Canning R., Ojah C., Monterrosa L., Dunn M., Sorokan T., Harrison A., Nwaesei C., Adie M., Hakansson S., Segerdahl N., Morad T., Moren S., Stenberg A., Simonsson C., Stigsson L., Christensen J.L., Amasn L., Ingemanson F., osterdal L., Ellstrom K.-G., Abrahamsson T., Heimdahl I., Hagg T., Hedlund A., Lund E.E., Westrup B., Sarman I., Jobe A.S., Fredsriksson M., Palm A., Malmstrom B., Lindberg E., Ljungdahl O., Eriksson K., Koller-Smith L.I.M., Shah P., Ye X.Y., Sjors G., Wang Y.A., Chow S.S.W., Darlow B.A., Lee S.K., Hakanson S., Lui K., Marshall P., Craven P., Simmer K., Stack J., Knight D., Watkins A., Ramsden A., Tan K., Bawden K., Downe L., Singde V., Stewart M., Berry A., Hunt R., Kilburn C., Dargaville P., Paradisis M., Evans N., Reid S., Cartwright D., Kuschel C., Doyle L., Numa A., Kecskes Z., Badawi N., Koh G., Resnick S., Tracy M., and Tarnow-Mordi W.

Abstract

Background: Compared to very low gestational age (<32 weeks, VLGA) cohorts, very low birth weight (<1500 g; VLBW) cohorts are more prone to selection bias toward small-for-gestational age (SGA) infants, which may impact upon the validity of data for benchmarking purposes. Method(s): Data from all VLGA or VLBW infants admitted in the 3 Networks between 2008 and 2011 were used. Two-thirds of each network cohort was randomly selected to develop prediction models for mortality and composite adverse outcome (CAO: mortality or cerebral injuries, chronic lung disease, severe retinopathy or necrotizing enterocolitis) and the remaining for internal validation. Areas under the ROC curves (AUC) of the models were compared. Result(s): VLBW cohort (24,335 infants) had twice more SGA infants (20.4% vs. 9.3%) than the VLGA cohort (29,180 infants) and had a higher rate of CAO (36.5% vs. 32.6%). The two models had equal prediction power for mortality and CAO (AUC 0.83), and similarly for all other cross-cohort validations (AUC 0.81-0.85). Neither model performed well for the extremes of birth weight for gestation (<1500 g and >=32 weeks, AUC 0.50-0.65; >=1500 g and <32 weeks, AUC 0.60-0.62). Conclusion(s): There was no difference in prediction power for adverse outcome between cohorting VLGA or VLBW despite substantial bias in SGA population. Either cohorting practises are suitable for international benchmarking.Copyright © 2017 The Author(s).

Published
2017

32. Genome-Wide Association Study for Incident Myocardial Infarction and Coronary Heart Disease in Prospective Cohort Studies: The CHARGE Consortium

Author

Dehghan, A. (Abbas), Bis, J.C. (Joshua), White, C.C. (Charles), Smith, A.V. (Albert V.), Morrison, A.C. (Alanna), Cupples, L.A. (Adrienne), Trompet, S. (Stella), Chasman, D.I. (Daniel I.), Lumley, T. (Thomas), Völker, U. (Uwe), Buckley, B.M. (Brendan M.), Ding, J. (Jingzhong), Jensen, M.K. (Majken K.), Folsom, A.R. (Aaron R.), Kritchevsky, S.B. (Stephen), Girman, C.J. (Cynthia J.), Ford, I., Dörr, M. (Marcus), Salomaa, V. (Veikko), Uitterlinden, A.G. (André), Eiriksdottir, G. (Gudny), Vasan, R.S. (Ramachandran S.), Franceschini, N. (Nora), Carty, C. (Cara), Virtamo, J. (Jarmo), Demissie, S. (Serkalem), Amouyel, P. (Philippe), Arveiler, D. (Dominique), Heckbert, S.R. (Susan), Ferrieres, J. (Jean), Ducimetiere, P. (P.), Smith, N.L. (Nicholas), Wang, Y.A. (Ying), Siscovick, D.S. (David), Rice, K.M. (Kenneth), Wiklund, P.-G. (Per-Gunnar), Taylor, K.D. (Kent), Evans, A. (Alun), Kee, F. (Frank), Rotter, J.I. (Jerome I.), Karvanen, J. (Juha), Kuulasmaa, K. (Kari), Heiss, G. (Gerardo), Kraft, P. (Peter), Launer, L.J. (Lenore), Hofman, A. (Albert), Markus, M.R.P. (Marcello R.P.), Rose, L.M. (Lynda), Silander, K. (Kaisa), Wagner, P.J. (Peter), Benjamin, E.J. (Emelia), Lohman, K. (Kurt), Stott, D.J. (David. J.), Rivadeneira Ramirez, F. (Fernando), Harris, T.B. (Tamara), Levy, D. (Daniel), Liu, Y. (YongMei), Rimm, E.B. (Eric B.), Jukema, J.W. (Jan Wouter), Volzke, H. (Henry), Ridker, P.M. (Paul M.), Blankenberg, S. (Stefan), Franco, O.H. (Oscar), Gudnason, V. (Vilmundur), Psaty, B.M. (Bruce), Boerwinkle, E.A. (Eric), O'Donnell, C.J. (Christopher J.), Dehghan, A. (Abbas), Bis, J.C. (Joshua), White, C.C. (Charles), Smith, A.V. (Albert V.), Morrison, A.C. (Alanna), Cupples, L.A. (Adrienne), Trompet, S. (Stella), Chasman, D.I. (Daniel I.), Lumley, T. (Thomas), Völker, U. (Uwe), Buckley, B.M. (Brendan M.), Ding, J. (Jingzhong), Jensen, M.K. (Majken K.), Folsom, A.R. (Aaron R.), Kritchevsky, S.B. (Stephen), Girman, C.J. (Cynthia J.), Ford, I., Dörr, M. (Marcus), Salomaa, V. (Veikko), Uitterlinden, A.G. (André), Eiriksdottir, G. (Gudny), Vasan, R.S. (Ramachandran S.), Franceschini, N. (Nora), Carty, C. (Cara), Virtamo, J. (Jarmo), Demissie, S. (Serkalem), Amouyel, P. (Philippe), Arveiler, D. (Dominique), Heckbert, S.R. (Susan), Ferrieres, J. (Jean), Ducimetiere, P. (P.), Smith, N.L. (Nicholas), Wang, Y.A. (Ying), Siscovick, D.S. (David), Rice, K.M. (Kenneth), Wiklund, P.-G. (Per-Gunnar), Taylor, K.D. (Kent), Evans, A. (Alun), Kee, F. (Frank), Rotter, J.I. (Jerome I.), Karvanen, J. (Juha), Kuulasmaa, K. (Kari), Heiss, G. (Gerardo), Kraft, P. (Peter), Launer, L.J. (Lenore), Hofman, A. (Albert), Markus, M.R.P. (Marcello R.P.), Rose, L.M. (Lynda), Silander, K. (Kaisa), Wagner, P.J. (Peter), Benjamin, E.J. (Emelia), Lohman, K. (Kurt), Stott, D.J. (David. J.), Rivadeneira Ramirez, F. (Fernando), Harris, T.B. (Tamara), Levy, D. (Daniel), Liu, Y. (YongMei), Rimm, E.B. (Eric B.), Jukema, J.W. (Jan Wouter), Volzke, H. (Henry), Ridker, P.M. (Paul M.), Blankenberg, S. (Stefan), Franco, O.H. (Oscar), Gudnason, V. (Vilmundur), Psaty, B.M. (Bruce), Boerwinkle, E.A. (Eric), and O'Donnell, C.J. (Christopher J.)

Abstract

Background Data are limited on genome-wide association studies (GWAS) for incident coronary heart disease (CHD). Moreover, it is not known whether genetic variants identified to date also associate with risk of CHD in a prospective setting. Methods We performed a two-stageGWAS analysis of incident myocardial infarction (MI) and CHD in a total of 64,297 individuals (including 3898MI cases, 5465 CHD cases). SNPs that passed an arbitrary threshold of 5×10-6 in Stage I were taken to Stage II for further discovery. Furthermore, in an analysis of prognosis, we studied whether known SNPs from former GWAS were associated with totalmortality in individuals who experienced MI during follow-up. Results In Stage I 15 loci passed the threshold of 5×10-6; 8 loci for MI and 8 loci for CHD, for which one locus overlapped and none were reported in previous GWAS meta-analyses. We took 60 SNPs representing these 15 loci to Stage II of discovery. Four SNPs near QKI showed nominally significant association with MI (p-value<8.8×10-3) and three exceeded the genome-wide significance threshold when Stage I and Stage II results were combined (top SNP rs6941513: p = 6.2×10-9). Despite excellent power, the 9p21 locus SNP (rs1333049) was only modestly associated with MI (HR = 1.09, p-value = 0.02) and marginally with CHD (HR = 1.06, p-value = 0.08). Among an inception cohort of those who experienced MI during follow-up, the risk allele of rs1333049 was associated with a decreased risk of subsequent mortality (HR = 0.90, p-value = 3.2×10-3). Conclusions QKI represents a novel locus that may serve as a predictor of incident CHD in prospective studies. The association of the 9p21 locus both with increased risk of first myocardial infarction and longer survival after MI highlights the importance of study design in investigating genetic determinants of complex disorders.

Published
2016
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33. Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function

Author

UCL - SSS/IREC/NEFR - Pôle de Néphrologie, UCL - (SLuc) Service de néphrologie, Pattaro, C., Teumer, A., Gorski, M., Chu, A.Y., Li, M., Mijatovic, V., Garnaas, M., Tin, A., Sorice, R., Li, Y., Taliun, D., Olden, M., Foster, M., Yang, Q., Chen, M.-H., Pers, T.H., Johnson, A.D., Ko, Y.-A., Fuchsberger, C., Tayo, B., Nalls, M., Feitosa, M.F., Isaacs, A., Dehghan, A., D'Adamo, P., Adeyemo, A., Dieffenbach, A.K., Zonderman, A.B., Nolte, I.M., Van Der Most, P.J., Wright, A.F., Shuldiner, A.R., Morrison, A.C., Hofman, A., Smith, A.V., Dreisbach, A.W., Franke, A., Uitterlinden, A.G., Metspalu, A., Tonjes, A., Lupo, A., Robino, A., Johansson, Å., Demirkan, A., Kollerits, B., Freedman, B.I., Ponte, B., Oostra, B.A., Paulweber, B., Krämer, B.K., Mitchell, B.D., Buckley, B.M., Peralta, C.A., Hayward, C., Helmer, C., Rotimi, C.N., Shaffer, C.M., Müller, C., Sala, C., Van Duijn, C.M., Saint-Pierre, A., Ackermann, D., Shriner, D., Ruggiero, D., Toniolo, D., Lu, Y., Cusi, D., Czamara, D., Ellinghaus, D., Siscovick, D.S., Ruderfer, D., Gieger, C., Grallert, H., Rochtchina, E., Atkinson, E.J., Holliday, E.G., Boerwinkle, E., Salvi, E., Bottinger, E.P., Murgia, F., Rivadeneira, F., Ernst, F., Kronenberg, F., Hu, F.B., Navis, G.J., Curhan, G.C., Ehret, G.B., Homuth, G., Coassin, S., Thun, G.-A., Pistis, G., Gambaro, G., Malerba, G., Montgomery, G.W., Eiriksdottir, G., Jacobs, G., Li, G., Wichmann, H.-E., Campbell, H., Schmidt, H., Wallaschofski, H., Völzke, H., Brenner, H., Kroemer, H.K., Kramer, H., Lin, H., Leach, I.M., Ford, I., Guessous, I., Rudan, I., Prokopenko, I., Borecki, I., Heid, I.M., Kolcic, I., Persico, I., Jukema, J.W., Wilson, J.F., Felix, J.F., Divers, J., Lambert, J.-C., Stafford, J.M., Gaspoz, J.-M., Smith, J.A., Faul, J.D., Wang, J.J., Ding, J., Hirschhorn, J.N., Attia, J., Whitfield, J.B., Chalmers, J., Viikari, J., Coresh, J., Denny, J.C., Karjalainen, J., Fernandes, J.K., Endlich, K., Butterbach, K., Keene, K.L., Lohman, K., Portas, L., Launer, L.J., Lyytikäinen, L.-P., Yengo, L., Franke, L., Ferrucci, L., Rose, L.M., Kedenko, L., Rao, M., Struchalin, M., Kleber, M.E., Cavalieri, M., Haun, M., Cornelis, M.C., Ciullo, M., Pirastu, M., De Andrade, M., McEvoy, M.A., Woodward, M., Adam, M., Cocca, M., Nauck, M., Imboden, M., Waldenberger, M., Pruijm, M., Metzger, M., Stumvoll, M., Evans, M.K., Sale, M.M., Kähönen, M., Boban, M., Bochud, M., Rheinberger, M., Verweij, N., Bouatia-Naji, N., Martin, N.G., Hastie, N., Probst-Hensch, N., Soranzo, N., Devuyst, O., Raitakari, O., Gottesman, O., Franco, O.H., Polasek, O., Gasparini, P., Munroe, P.B., Ridker, P.M., Mitchell, P., Muntner, P., Meisinger, C., Smit, J.H., Abecasis, G.R., Adair, L.S., Alexander, M., Altshuler, D., Amin, N., Arking, D.E., Arora, P., Aulchenko, Y., Bakker, S.J.L., Bandinelli, S., Barroso, I., Beckmann, J.S., Beilby, J.P., Bergman, R.N., Bergmann, S., Bis, J.C., Boehnke, M., Bonnycastle, L.L., Bornstein, S.R., Bots, M.L., Bragg-Gresham, J.L., Brand, S.-M., Brand, E., Braund, P.S., Brown, M.J., Burton, P.R., Casas, J.P., Caulfield, M.J., Chakravarti, A., Chambers, J.C., Chandak, G.R., Chang, Y.-P.C., Charchar, F.J., Chaturvedi, N., Cho, Y.S., Clarke, R., Collins, F.S., Collins, R., Connell, J.M., Cooper, J.A., Cooper, M.N., Cooper, R.S., Corsi, A.M., Dörr, M., Dahgam, S., Danesh, J., Smith, G.D., Day, I.N.M., Deloukas, P., Denniff, M., Dominiczak, A.F., Dong, Y., Doumatey, A., Elliott, P., Elosua, R., Erdmann, J., Eyheramendy, S., Farrall, M., Fava, C., Forrester, T., Fowkes, F.G.R., Fox, E.R., Frayling, T.M., Galan, P., Ganesh, S.K., Garcia, M., Gaunt, T.R., Glazer, N.L., Go, M.J., Goel, A., Grässler, J., Grobbee, D.E., Groop, L., Guarrera, S., Guo, X., Hadley, D., Hamsten, A., Han, B.-G., Hardy, R., Hartikainen, A.-L., Heath, S., Heckbert, S.R., Hedblad, B., Hercberg, S., Hernandez, D., Hicks, A.A., Hilton, G., Hingorani, A.D., Hoffman Bolton, J.A., Hopewell, J.C., Howard, P., Humphries, S.E., Hunt, S.C., Hveem, K., Ikram, M.A., Islam, M., Iwai, N., Jarvelin, M.-R., Jackson, A.U., Jafar, T.H., Janipalli, C.S., Johnson, T., Kathiresan, S., Khaw, K.-T., Kim, H.-L., Kinra, S., Kita, Y., Kivimaki, M., Kooner, J.S., Kumar, M.J.K., Kuh, D., Kulkarni, S.R., Kumari, M., Kuusisto, J., Kuznetsova, T., Laakso, M., Laan, M., Laitinen, J., Lakatta, E.G., Langefeld, C.D., Larson, M.G., Lathrop, M., Lawlor, D.A., Lawrence, R.W., Lee, J.-Y., Lee, N.R., Levy, D., Longstreth, W.T., Luan, J., Lucas, G., Ludwig, B., Mangino, M., Mani, K.R., Marmot, M.G., Mattace-Raso, F.U.S., Matullo, G., McArdle, W.L., McKenzie, C.A., Meitinger, T., Melander, O., Meneton, P., Meschia, J.F., Miki, T., Milaneschi, Y., Mohlke, K.L., Mooser, V., Morken, M.A., Morris, R.W., Mosley, T.H., Najjar, S., Narisu, N., Newton-Cheh, C., Nguyen, K.-D.H., Nilsson, P., Nyberg, F., O'Donnell, C.J., Ogihara, T., Ohkubo, T., Okamura, T., Ong, R.T.-H., Ongen, H., Onland-Moret, N.C., O'Reilly, P.F., Org, E., Orru, M., Palmas, W., Palmen, J., Palmer, L.J., Palmer, N.D., Parker, A.N., Peden, J.F., 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Wong, T.-Y., Liu, J., Young, T.L., Aung, T., Teo, Y.-Y., Kim, Y.J., Kang, D., Chen, C.-H., Tsai, F.-J., Chang, L.-C., Fann, S.-J.C., Mei, H., Hixson, J.E., Chen, S., Katsuya, T., Isono, M., Albrecht, E., Yamamoto, K., Kubo, M., Nakamura, Y., Kamatani, N., Kato, N., He, J., Chen, Y.-T., Tanaka, T., Reilly, M.P., Schunkert, H., Assimes, T.L., Hall, A., Hengstenberg, C., König, I.R., Laaksonen, R., McPherson, R., Thompson, J.R., Thorsteinsdottir, U., Ziegler, A., Absher, D., Chen, L., Cupples, L.A., Halperin, E., Musunuru, K., Preuss, M., Schillert, A., Thorleifsson, G., Wells, G.A., Holm, H., Roberts, R., Stewart, A.F.R., 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, K.J., Tiret, L., Nicaud, V., Cambien, F., Bickel, C., Rupprecht, H.J., Perret, C., Proust, C., Münzel, T.F., Barbalic, M., Chen, I.Y.-D., Demissie-Banjaw, S., Folsom, A., Lumley, T., Marciante, K., Taylor, K.D., Volcik, K., Gretarsdottir, S., Gulcher, J.R., 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, A.K., Willenborg, C., Böhm, B.O., Dobnig, H., Grammer, T.B., Hoffmann, M.M., Meinitzer, A., Winkelmann, B.R., Pilz, S., Renner, W., Scharnagl, H., Stojakovic, T., Tomaschitz, A., Winkler, K., Guiducci, C., Burtt, N., Gabriel, S.B., Dandona, S., Jarinova, O., Qu, L., Wilensky, R., Matthai, W., Hakonarson, H.H., Devaney, J., Burnett, M.S., Pichard, A.D., Kent, K.M., Satler, L., Lindsay, J.M., Waksman, R., Knouff, C.W., Waterworth, D.M., Walker, M.C., Epstein, S.E., Rader, D.J., Nelson, C.P., Wright, B.J., Balmforth, A.J., Ball, S.G., Loehr, L.R., Rosamond, W.D., Benjamin, E., Haritunians, T., Couper, D., Murabito, J., Wang, Y.A., Stricker, B.H., Chang, P.P., Willerson, J.T., Felix, S.B., Watzinger, N., Aragam, J., Zweiker, R., Lind, L., Rodeheffer, R.J., Greiser, K.H., Deckers, J.W., Stritzke, J., Ingelsson, E., Kullo, I., Haerting, J., Reffelmann, T., Redfield, M.M., Werdan, K., Mitchell, G.F., Arnett, D.K., Gottdiener, J.S., Blettner, M., Friedrich, N., Kovacs, P., Wild, P.S., Froguel, P., Rettig, R., Mägi, R., Biffar, R., Schmidt, R., Middelberg, R.P.S., Carroll, R.J., Penninx, B.W., Scott, R.J., Katz, R., Sedaghat, S., Wild, S.H., Kardia, S.L.R., Ulivi, S., Hwang, S.-J., Enroth, S., Kloiber, S., Trompet, S., Stengel, B., Hancock, S.J., Turner, S.T., Rosas, S.E., Stracke, S., Harris, T.B., Zeller, T., Zemunik, T., Lehtimäki, T., Illig, T., Aspelund, T., Nikopensius, T., Esko, T., Gyllensten, U., Völker, U., Emilsson, V., Vitart, V., Aalto, V., Gudnason, V., Chouraki, V., Chen, W.-M., Igl, W., März, W., Koenig, W., Lieb, W., Loos, R.J.F., Liu, Y., Snieder, H., Pramstaller, P.P., Parsa, A., O'Connell, J.R., Susztak, K., Hamet, P., Tremblay, J., De Boer, I.H., Böger, C.A., Goessling, W., Chasman, D.I., Köttgen, A., Kao, W.H.L., and Fox, C.S.

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. © 2016, Nature Publishing Group. All rights reserved.

Published
2016

35. Common variation in fatty acid metabolic genes and risk of incident sudden cardiac arrest

Author

Lemaitre, R.N. (Rozenn ), Johnson, C.O. (Catherine), Hesselson, S. (Stephanie), Sotoodhenia, N. (Nona), McKnight, B. (Barbara), Sitlani, C.M. (Colleen), Rea, D. (Dan), King, I.B. (Irena), Kwok, P.-Y. (Pui-Yan), Mak, A. (Angel), Li, G. (Guo), Brody, J.A. (Jennifer A.), Larson, E.B. (Eric), Mozaffarian, D. (Dariush), Psaty, B.M. (Bruce), Huertas-Vazquez, A. (Adriana), Tardif, J.-C. (Jean-Claude), Albert, C.M. (Christine), Lyytikäinen, L.-P. (Leo-Pekka), Arking, D.E. (Dan), Kääb, S. (Stefan), Huikuri, H.V. (Heikki), Krijthe, B.P. (Bouwe), Eijgelsheim, M. (Mark), Wang, Y.A. (Ying), Reinier, K. (Kyndaron), Lehtimäki, T. (Terho), Pulit, S.L. (Sara), Brugada, R. (Ramon), Müller-Nurasyid, M. (Martina), Newton-Cheh, C. (Christopher), Karhunen, P.J. (Pekka), Stricker, B.H.Ch. (Bruno), Goyette, P. (Philippe), Rotter, J.I. (Jerome), Chugh, S.S. (Sumeet), Chakravarti, A. (Aravinda), Jouven, X. (Xavier), Siscovick, D.S. (David), Lemaitre, R.N. (Rozenn ), Johnson, C.O. (Catherine), Hesselson, S. (Stephanie), Sotoodhenia, N. (Nona), McKnight, B. (Barbara), Sitlani, C.M. (Colleen), Rea, D. (Dan), King, I.B. (Irena), Kwok, P.-Y. (Pui-Yan), Mak, A. (Angel), Li, G. (Guo), Brody, J.A. (Jennifer A.), Larson, E.B. (Eric), Mozaffarian, D. (Dariush), Psaty, B.M. (Bruce), Huertas-Vazquez, A. (Adriana), Tardif, J.-C. (Jean-Claude), Albert, C.M. (Christine), Lyytikäinen, L.-P. (Leo-Pekka), Arking, D.E. (Dan), Kääb, S. (Stefan), Huikuri, H.V. (Heikki), Krijthe, B.P. (Bouwe), Eijgelsheim, M. (Mark), Wang, Y.A. (Ying), Reinier, K. (Kyndaron), Lehtimäki, T. (Terho), Pulit, S.L. (Sara), Brugada, R. (Ramon), Müller-Nurasyid, M. (Martina), Newton-Cheh, C. (Christopher), Karhunen, P.J. (Pekka), Stricker, B.H.Ch. (Bruno), Goyette, P. (Philippe), Rotter, J.I. (Jerome), Chugh, S.S. (Sumeet), Chakravarti, A. (Aravinda), Jouven, X. (Xavier), and Siscovick, D.S. (David)

Abstract

Background There is limited information on genetic factors associated with sudden cardiac arrest (SCA). Objective To assess the association of common variation in genes in fatty acid pathways with SCA risk. Methods We selected 85 candidate genes and 1155 single nucleotide polymorphisms (SNPs) tagging common variation in each gene. We investigated the SNP associations with SCA in a population-based case-control study. Cases (n = 2160) were from a repository of SCA in the greater Seattle area. Controls (n = 2615), frequency-matched on age and sex, were from the same area. We used linear logistic regression to examine SNP associations with SCA. We performed permutation-based p-min tests to account for multiple comparisons within each gene. The SNP associations with a corrected P value of <.05 were then examined in a meta-analysis of these SNP associations in 9 replication studies totaling 2129 SCA cases and 23,833 noncases. Results Eight SNPs in or near 8 genes were associated with SCA risk in the discovery study, one of which was nominally significant in the replication phase (rs7737692, minor allele frequency 36%, near the LPCAT1 gene). For each copy of the minor allele, rs7737692 was associated with 13% lower SCA risk (95% confidence interval -21% to -5%) in the discovery phase and 9% lo

Published
2014
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36. Discovery and fine mapping of serum protein loci through transethnic meta-analysis

Author

Franceschini, N. (Nora), Rooij, F.J.A. (Frank) van, Prins, B.P. (Bram), Feitosa, M.F. (Mary Furlan), Karakas, M. (Mahir), Eckfeldt, J.H. (John), Folsom, A.R. (Aaron), Kopp, J. (Jeffrey), Vaez, A. (Ahmad), Andrews, J.S. (Jeanette), Baumert, J. (Jens), Boraska, V. (Vesna), Broer, L. (Linda), Hayward, C. (Caroline), Ngwa, J.S., Okada, Y. (Yukinori), Polasek, O. (Ozren), Westra, H.J. (Harm-Jan), Wang, Y.A. (Ying), Del Greco, F. (Fabiola), Glazer, N.L. (Nicole), Kapur, K. (Karen), Kema, I.P. (Ido), Lopez, L.M. (Lorna), Schillert, A. (Arne), Smith, A.V. (Davey), Winkler, C.A. (Cheryl), Zgaga, L. (Lina), Bandinelli, S. (Stefania), Bergmann, S.M. (Sven), Boban, M. (Mladen), Bochud, M. (Murielle), Chen, Y.D. (Y.), Davies, G. (Gail), Dehghan, A. (Abbas), Ding, J. (Jingzhong), Doering, A. (Angela), Durda, J.P. (J. Peter), Ferrucci, L. (Luigi), Franco, O.H. (Oscar), Franke, L. (Lude), Gunjaca, G. (Grog), Hofman, A. (Albert), Hsu, F.-C. (Fang-Chi), Kolcic, I. (Ivana), Kraja, A. (Aldi), Kubo, M. (Michiaki), Lackner, K.J. (Karl), Launer, L.J. (Lenore), Loehr, L.R. (Laura), Li, G. (Guo), Meisinger, C. (Christa), Nakamura, Y. (Yusuke), Schwienbacher, C. (Christine), Starr, J.M. (John), Takahashi, A. (Atsushi), Torlak, V. (Vesela), Uitterlinden, A.G. (André), Vitart, V. (Veronique), Waldenberger, M. (Melanie), Wild, P.S. (Philipp), Kirin, M. (Mirna), Zeller, T. (Tanja), Zemunik, T. (Tatijana), Zhang, Q. (Qunyuan), Ziegler, A. (Andreas), Blankenberg, S. (Stefan), Boerwinkle, E.A. (Eric), Borecki, I.B. (Ingrid), Campbell, H. (Harry), Deary, I.J. (Ian), Frayling, T.M. (Timothy), Gieger, C. (Christian), Harris, T.B. (Tamara), Hicks, A.A. (Andrew), Koenig, W. (Wolfgang), O'Donnell, C.J. (Christopher), Fox, C. (Craig), Pramstaller, P.P. (Peter Paul), Psaty, B.M. (Bruce), Reiner, A. (Alexander), Rotter, J.I. (Jerome), Rudan, I. (Igor), Snieder, H. (Harold), Tanaka, T. (Toshiko), Duijn, C.M. (Cornelia) van, Vollenweider, P. (Peter), Waeber, G. (Gérard), Wilson, J.F. (James), Witteman, J.C.M. (Jacqueline), Wolffenbuttel, B.H.R. (Bruce), Wright, A.F. (Alan), Wu, Q. (Qingyu), Liu, Y. (YongMei), Jenny, N.S. (Nancy), North, K.E. (Kari), Felix, J.F. (Janine), Alizadeh, B.Z. (Behrooz), Cupples, L.A. (Adrienne), Perry, J.R.B. (John), Morris, A.P. (Andrew), Franceschini, N. (Nora), Rooij, F.J.A. (Frank) van, Prins, B.P. (Bram), Feitosa, M.F. (Mary Furlan), Karakas, M. (Mahir), Eckfeldt, J.H. (John), Folsom, A.R. (Aaron), Kopp, J. (Jeffrey), Vaez, A. (Ahmad), Andrews, J.S. (Jeanette), Baumert, J. (Jens), Boraska, V. (Vesna), Broer, L. (Linda), Hayward, C. (Caroline), Ngwa, J.S., Okada, Y. (Yukinori), Polasek, O. (Ozren), Westra, H.J. (Harm-Jan), Wang, Y.A. (Ying), Del Greco, F. (Fabiola), Glazer, N.L. (Nicole), Kapur, K. (Karen), Kema, I.P. (Ido), Lopez, L.M. (Lorna), Schillert, A. (Arne), Smith, A.V. (Davey), Winkler, C.A. (Cheryl), Zgaga, L. (Lina), Bandinelli, S. (Stefania), Bergmann, S.M. (Sven), Boban, M. (Mladen), Bochud, M. (Murielle), Chen, Y.D. (Y.), Davies, G. (Gail), Dehghan, A. (Abbas), Ding, J. (Jingzhong), Doering, A. (Angela), Durda, J.P. (J. Peter), Ferrucci, L. (Luigi), Franco, O.H. (Oscar), Franke, L. (Lude), Gunjaca, G. (Grog), Hofman, A. (Albert), Hsu, F.-C. (Fang-Chi), Kolcic, I. (Ivana), Kraja, A. (Aldi), Kubo, M. (Michiaki), Lackner, K.J. (Karl), Launer, L.J. (Lenore), Loehr, L.R. (Laura), Li, G. (Guo), Meisinger, C. (Christa), Nakamura, Y. (Yusuke), Schwienbacher, C. (Christine), Starr, J.M. (John), Takahashi, A. (Atsushi), Torlak, V. (Vesela), Uitterlinden, A.G. (André), Vitart, V. (Veronique), Waldenberger, M. (Melanie), Wild, P.S. (Philipp), Kirin, M. (Mirna), Zeller, T. (Tanja), Zemunik, T. (Tatijana), Zhang, Q. (Qunyuan), Ziegler, A. (Andreas), Blankenberg, S. (Stefan), Boerwinkle, E.A. (Eric), Borecki, I.B. (Ingrid), Campbell, H. (Harry), Deary, I.J. (Ian), Frayling, T.M. (Timothy), Gieger, C. (Christian), Harris, T.B. (Tamara), Hicks, A.A. (Andrew), Koenig, W. (Wolfgang), O'Donnell, C.J. (Christopher), Fox, C. (Craig), Pramstaller, P.P. (Peter Paul), Psaty, B.M. (Bruce), Reiner, A. (Alexander), Rotter, J.I. (Jerome), Rudan, I. (Igor), Snieder, H. (Harold), Tanaka, T. (Toshiko), Duijn, C.M. (Cornelia) van, Vollenweider, P. (Peter), Waeber, G. (Gérard), Wilson, J.F. (James), Witteman, J.C.M. (Jacqueline), Wolffenbuttel, B.H.R. (Bruce), Wright, A.F. (Alan), Wu, Q. (Qingyu), Liu, Y. (YongMei), Jenny, N.S. (Nancy), North, K.E. (Kari), Felix, J.F. (Janine), Alizadeh, B.Z. (Behrooz), Cupples, L.A. (Adrienne), Perry, J.R.B. (John), and Morris, A.P. (Andrew)

Abstract

Many disorders are associated with altered serum protein concentrations, including malnutrition, cancer, and cardiovascular, kidney, and inflammatory diseases. Although these protein concentrations are highly heritable, relatively little is known about their underlying genetic determinants. Through transethnic meta-analysis of European-ancestry and Japanese genome-wide association studies, we identified six loci at genome-wide significance (p < 5 × 10-8) for serum albumin (HPN-SCN1B, GCKR-FNDC4, SERPINF2-WDR81, TNFRSF11A-ZCCHC2, FRMD5-WDR76, and RPS11-FCGRT, in up to 53,190 European-ancestry and 9,380 Japanese individuals) and three loci for total protein (TNFRS13B, 6q21.3, and ELL2, in up to 25,539 European-ancestry and 10,168 Japanese individuals). We observed little evidence of heterogeneity in allelic effects at these loci between groups of European and Japanese ancestry but obtained substantial improvements in the resolution of fine mapping of potential causal variants by leveraging transethnic differences in the distribution of linkage disequilibrium. We demonstrated a functional role for the most strongly associated serum albumin locus, HPN, for which Hpn knockout mice manifest low plasma albumin concentrations.

Published
2012
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37. Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.

Author

International Consortium for Blood Pressure Genome-Wide Association Studies, CARDIoGRAM consortium, CKDGen Consortium, KidneyGen Consortium, EchoGen consortium, CHARGE-HF consortium, Ehret, G.B., Munroe, P.B., Rice, K.M., Bochud, M., Johnson, A.D., Chasman, D.I., Smith, A.V., Tobin, M.D., Verwoert, G.C., Hwang, S.J., Pihur, V., Vollenweider, P., O'Reilly, P.F., Amin, N., Bragg-Gresham, J.L., Teumer, A., Glazer, N.L., Launer, L., Zhao, J.H., Aulchenko, Y., Heath, S., Sõber, S., Parsa, A., Luan, J., Arora, P., Dehghan, A., Zhang, F., Lucas, G., Hicks, A.A., Jackson, A.U., Peden, J.F., Tanaka, T., Wild, S.H., Rudan, I., Igl, W., Milaneschi, Y., Parker, A.N., Fava, C., Chambers, J.C., Fox, E.R., Kumari, M., Go, M.J., van der Harst, P., Kao, W.H., Sjögren, M., Vinay, D.G., Alexander, M., Tabara, Y., Shaw-Hawkins, S., Whincup, P.H., Liu, Y., Shi, G., Kuusisto, J., Tayo, B., Seielstad, M., Sim, X., Nguyen, K.D., Lehtimäki, T., Matullo, G., Wu, Y., Gaunt, T.R., Onland-Moret, N.C., Cooper, M.N., Platou, C.G., Org, E., Hardy, R., Dahgam, S., Palmen, J., Vitart, V., Braund, P.S., Kuznetsova, T., Uiterwaal, C.S., Adeyemo, A., Palmas, W., Campbell, H., Ludwig, B., Tomaszewski, M., Tzoulaki, I., Palmer, N.D., Aspelund, T., Garcia, M., Chang, Y.P., O'Connell, J.R., Steinle, N.I., Grobbee, D.E., Arking, D.E., Kardia, S.L., Morrison, A.C., Hernandez, D., Najjar, S., McArdle, W.L., Hadley, D., Brown, M.J., Connell, J.M., Hingorani, A.D., Day, I.N., Lawlor, D.A., Beilby, J.P., Lawrence, R.W., Clarke, R., Hopewell, J.C., Ongen, H., Dreisbach, A.W., Li, Y., Young, J.H., Bis, J.C., Kähönen, M., Viikari, J., Adair, L.S., Lee, N.R., Chen, M.H., Olden, M., Pattaro, C., Bolton, J.A., Köttgen, A., Bergmann, S., Mooser, V., Chaturvedi, N., Frayling, T.M., Islam, M., Jafar, T.H., Erdmann, J., Kulkarni, S.R., Bornstein, S.R., Grässler, J., Groop, L., Voight, B.F., Kettunen, J., Howard, P., Taylor, A., Guarrera, S., Ricceri, F., Emilsson, V., Plump, A., Barroso, I., Khaw, K.T., Weder, A.B., Hunt, S.C., Sun, Y.V., Bergman, R.N., Collins, F.S., Bonnycastle, L.L., Scott, L.J., Stringham, H.M., Peltonen, L., Perola, M., Vartiainen, E., Brand, S.M., Staessen, J.A., Wang, T.J., Burton, P.R., Artigas, M.S., Dong, Y., Snieder, H., Wang, X., Zhu, H., Lohman, K.K., Rudock, M.E., Heckbert, S.R., Smith, N.L., Wiggins, K.L., Doumatey, A., Shriner, D., Veldre, G., Viigimaa, M., Kinra, S., Prabhakaran, D., Tripathy, V., Langefeld, C.D., Rosengren, A., Thelle, D.S., Corsi, A.M., Singleton, A., Forrester, T., Hilton, G., McKenzie, C.A., Salako, T., Iwai, N., Kita, Y., Ogihara, T., Ohkubo, T., Okamura, T., Ueshima, H., Umemura, S., Eyheramendy, S., Meitinger, T., Wichmann, H.E., Cho, Y.S., Kim, H.L., Lee, J.Y., Scott, J., Sehmi, J.S., Zhang, W., Hedblad, B., Nilsson, P., Smith, G.D., Wong, A., Narisu, N., Stančáková, A., Raffel, L.J., Yao, J., Kathiresan, S., O'Donnell, C.J., Schwartz, S.M., Ikram, M.A., Longstreth, W.T., Mosley, T.H., Seshadri, S., Shrine, N.R., Wain, L.V., Morken, M.A., Swift, A.J., Laitinen, J., Prokopenko, I., Zitting, P., Cooper, J.A., Humphries, S.E., Danesh, J., Rasheed, A., Goel, A., Hamsten, A., Watkins, H., Bakker, S.J., van Gilst, W.H., Janipalli, C.S., Mani, K.R., Yajnik, C.S., Hofman, A., Mattace-Raso, F.U., Oostra, B.A., Demirkan, A., Isaacs, A., Rivadeneira, F., Lakatta, E.G., Orru, M., Scuteri, A., Ala-Korpela, M., Kangas, A.J., Lyytikäinen, L.P., Soininen, P., Tukiainen, T., Würtz, P., Ong, R.T., Dörr, M., Kroemer, H.K., Völker, U., Völzke, H., Galan, P., Hercberg, S., Lathrop, M., Zelenika, D., Deloukas, P., Mangino, M., Spector, T.D., Zhai, G., Meschia, J.F., Nalls, M.A., Sharma, P., Terzic, J., Kumar, M.V., Denniff, M., Zukowska-Szczechowska, E., Wagenknecht, L.E., Fowkes, F.G., Charchar, F.J., Schwarz, P.E., Hayward, C., Guo, X., Rotimi, C., Bots, M.L., Brand, E., Samani, N.J., Polasek, O., Talmud, P.J., Nyberg, F., Kuh, D., Laan, M., Hveem, K., Palmer, L.J., van der Schouw, Y.T., Casas, J.P., Mohlke, K.L., Vineis, P., Raitakari, O., Ganesh, S.K., Wong, T.Y., Tai, E.S., Cooper, R.S., Laakso, M., Rao, D.C., Harris, T.B., Morris, R.W., Dominiczak, A.F., Kivimaki, M., Marmot, M.G., Miki, T., Saleheen, D., Chandak, G.R., Coresh, J., Navis, G., Salomaa, V., Han, B.G., Zhu, X., Kooner, J.S., Melander, O., Ridker, P.M., Bandinelli, S., Gyllensten, U.B., Wright, A.F., Wilson, J.F., Ferrucci, L., Farrall, M., Tuomilehto, J., Pramstaller, P.P., Elosua, R., Soranzo, N., Sijbrands, E.J., Altshuler, D., Loos, R.J., Shuldiner, A.R., Gieger, C., Meneton, P., Uitterlinden, A.G., Wareham, N.J., Gudnason, V., Rotter, J.I., Rettig, R., Uda, M., Strachan, D.P., Witteman, J.C., Hartikainen, A.L., Beckmann, J.S., Boerwinkle, E., Vasan, R.S., Boehnke, M., Larson, M.G., Järvelin, M.R., Psaty, B.M., Abecasis, G.R., Chakravarti, A., Elliott, P., van Duijn, C.M., Newton-Cheh, C., Levy, D., Caulfield, M.J., Johnson, T., Tang, H., Knowles, J., Hlatky, M., Fortmann, S., Assimes, T.L., Quertermous, T., Go, A., Iribarren, C., Absher, D., Risch, N., Myers, R., Sidney, S., Ziegler, A., Schillert, A., Bickel, C., Sinning, C., Rupprecht, H.J., Lackner, K., Wild, P., Schnabel, R., Blankenberg, S., Zeller, T., Münzel, T., Perret, C., Cambien, F., Tiret, L., Nicaud, V., Proust, C., Uitterlinden, A., van Duijn, C., Whitteman, J., Cupples, L.A., Demissie-Banjaw, S., Ramachandran, V., Smith, A., Folsom, A., Morrison, A., Chen, I.Y., Bis, J., Volcik, K., Rice, K., Taylor, K.D., Marciante, K., Smith, N., Glazer, N., Heckbert, S., Harris, T., Lumley, T., Kong, A., Thorleifsson, G., Thorgeirsson, G., Holm, H., Gulcher, J.R., Stefansson, K., Andersen, K., Gretarsdottir, S., Thorsteinsdottir, U., Preuss, M., Schreiber, S., König, I.R., Lieb, W., Hengstenberg, C., Schunkert, H., Fischer, M., Grosshennig, A., Medack, A., Stark, K., Linsel-Nitschke, P., Bruse, P., Aherrahrou, Z., Peters, A., Loley, C., Willenborg, C., Nahrstedt, J., Freyer, J., Gulde, S., Doering, A., Meisinger, C., Klopp, N., Illig, T., Meinitzer, A., Tomaschitz, A., Halperin, E., Dobnig, H., Scharnagl, H., Kleber, M., Laaksonen, R., Pilz, S., Grammer, T.B., Stojakovic, T., Renner, W., März, W., Böhm, B.O., Winkelmann, B.R., Winkler, K., Hoffmann, M.M., Siscovick, D.S., Musunuru, K., Barbalic, M., Guiducci, C., Burtt, N., Gabriel, S.B., Stewart, A.F., Wells, G.A., Chen, L., Jarinova, O., Roberts, R., McPherson, R., Dandona, S., Pichard, A.D., Rader, D.J., Devaney, J., Lindsay, J.M., Kent, K.M., Qu, L., Satler, L., Burnett, M.S., Li, M., Reilly, M.P., Wilensky, R., Waksman, R., Epstein, S., Matthai, W., Knouff, C.W., Waterworth, D.M., Hakonarson, H.H., Walker, M.C., Hall, A.S., Balmforth, A.J., Wright, B.J., Nelson, C., Thompson, J.R., Ball, S.G., Felix, J.F., Demissie, S., Loehr, L.R., Rosamond, W.D., Folsom, A.R., Benjamin, E., Aulchenko, Y.S., Haritunians, T., Couper, D., Murabito, J., Wang, Y.A., Stricker, B.H., Gottdiener, J.S., Chang, P.P., Willerson, J.T., Böger, C.A., Fuchsberger, C., Gao, X., Yang, Q., Schmidt, H., Ketkar, S., Paré, G., Atkinson, E.J., Lohman, K., Cornelis, M.C., Probst-Hensch, N.M., Kronenberg, F., Tönjes, A., Eiriksdottir, G., Launer, L.J., Rampersaud, E., Mitchell, B.D., Struchalin, M., Cavalieri, M., Giallauria, F., Metter, J., de Boer, J., Siscovick, D., Zillikens, M.C., Feitosa, M., Province, M., de Andrade, M., Turner, S.T., Wild, P.S., Schnabel, R.B., Wilde, S., Munzel, T.F., Leak, T.S., Koenig, W., Zgaga, L., Zemunik, T., Kolcic, I., Minelli, C., Hu, F.B., Johansson, A., Zaboli, G., Ellinghaus, D., Imboden, M., Nitsch, D., Brandstätter, A., Kollerits, B., Kedenko, L., Mägi, R., Stumvoll, M., Kovacs, P., Boban, M., Campbell, S., Endlich, K., Nauck, M., Badola, S., Curhan, G.C., Franke, A., Rochat, T., Paulweber, B., Wang, W., Schmidt, R., Shlipak, M.G., Borecki, I., Krämer, B.K., Gyllensten, U., Hastie, N., Heid, I.M., Fox, C.S., Felix, S.B., Watzinger, N., Homuth, G., Aragam, J., Zweiker, R., Lind, L., Rodeheffer, R.J., Greiser, K.H., Deckers, J.W., Stritzke, J., Lackner, K.J., Ingelsson, E., Kullo, I., Haerting, J., Reffelmann, T., Redfield, M.M., Werdan, K., Mitchell, G.F., Arnett, D.K., Blettner, M., Friedrich, N., Benjamin, E.J., Lord, G.M., Gale, D.P., Wass, M.N., Ahmadi, K.R., Beckmann, J., Bilo, H.J., Cook, H.T., Cotlarciuc, I., Davey Smith, G., de Silva, R., Deng, G., Devuyst, O., Dikkeschei, L.D., Dimkovic, N., Dockrell, M., Dominiczak, A., Ebrahim, S., Eggermann, T., Floege, J., Forouhi, N.G., Gansevoort, R.T., Han, X., Homan van der Heide, J.J., Hepkema, B.G., Hernandez-Fuentes, M., Hypponen, E., de Jong, P.E., Kleefstra, N., Lagou, V., Lapsley, M., Luttropp, K., Maréchal, C., Nordfors, L., Penninx, B.W., Perucha, E., Pouta, A., Roderick, P.J., Ruokonen, A., Sanna, S., Schalling, M., Schlessinger, D., Schlieper, G., Seelen, M.A., Smit, J.H., Stenvinkel, P., Sternberg, M.J., Swaminathan, R., Ubink-Veltmaat, L.J., Wallace, C., Waterworth, D., Zerres, K., Waeber, G., Maxwell, P.H., McCarthy, M.I., Jarvelin, M.R., Lightstone, L., International Consortium for Blood Pressure Genome-Wide Association Studies, CARDIoGRAM consortium, CKDGen Consortium, KidneyGen Consortium, EchoGen consortium, CHARGE-HF consortium, Ehret, G.B., Munroe, P.B., Rice, K.M., Bochud, M., Johnson, A.D., Chasman, D.I., Smith, A.V., Tobin, M.D., Verwoert, G.C., Hwang, S.J., Pihur, V., Vollenweider, P., O'Reilly, P.F., Amin, N., Bragg-Gresham, J.L., Teumer, A., Glazer, N.L., Launer, L., Zhao, J.H., Aulchenko, Y., Heath, S., Sõber, S., Parsa, A., Luan, J., Arora, P., Dehghan, A., Zhang, F., Lucas, G., Hicks, A.A., Jackson, A.U., Peden, J.F., Tanaka, T., Wild, S.H., Rudan, I., Igl, W., Milaneschi, Y., Parker, A.N., Fava, C., Chambers, J.C., Fox, E.R., Kumari, M., Go, M.J., van der Harst, P., Kao, W.H., Sjögren, M., Vinay, D.G., Alexander, M., Tabara, Y., Shaw-Hawkins, S., Whincup, P.H., Liu, Y., Shi, G., Kuusisto, J., Tayo, B., Seielstad, M., Sim, X., Nguyen, K.D., Lehtimäki, T., Matullo, G., Wu, Y., Gaunt, T.R., Onland-Moret, N.C., Cooper, M.N., Platou, C.G., Org, E., Hardy, R., 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Abstract

Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention.

Published
2011

38. Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure

Author

Wain, L.V. (Louise), Verwoert, G.C. (Germaine), O'Reilly, P.F. (Paul), Shi, G. (Gang), Johnson, T. (Toby), Bochud, M. (Murielle), Rice, K. (Kenneth), Henneman, P. (Peter), Smith, A.V. (Albert Vernon), Ehret, G.B. (Georg), Amin, N. (Najaf), Larson, M.G. (Martin), Mooser, V. (Vincent), Hadley, D. (David), Dörr, M. (Marcus), Bis, J.C. (Joshua), Aspelund, T. (Thor), Esko, T. (Tõnu), Janssens, A.C.J.W. (Cécile), Zhao, J.H. (Jing Hua), Heath, S.C. (Simon), Laan, M. (Maris), Fu, J. (Jingyuan), Pistis, G. (Giorgio), Luan, J., Lucas, G. (Gavin), Pirastu, N. (Nicola), Pichler, I. (Irene), Jackson, A.U. (Anne), Webster, R.J. (Rebecca J.), Zhang, F.F., Peden, J. (John), Schmidt, R. (Reinhold), Tanaka, T. (Toshiko), Campbell, H. (Harry), Igl, W. (Wilmar), Milaneschi, Y. (Yuri), Hottenga, J.J. (Jouke Jan), Vitart, V. (Veronique), Chasman, D.I. (Daniel), Trompet, S. (Stella), Bragg-Gresham, J.L. (Jennifer L.), Alizadeh, B.Z. (Behrooz), Chambers, J.C. (John), Guo, X. (Xiuqing), Lehtimäki, T. (Terho), Kuhnel, B. (Brigitte), Lopez, L.M., Polasek, O. (Ozren), Boban, M. (Mladen), Nelson, C.P. (Christopher P.), Morrison, A.C. (Alanna), Pihur, V. (Vasyl), Ganesh, S.K. (Santhi), Hofman, A. (Albert), Kundu, S. (Suman), Mattace Raso, F.U.S. (Francesco), Rivadeneira Ramirez, F. (Fernando), Sijbrands, E.J.G. (Eric), Uitterlinden, A.G. (André), Hwang, S.J., Vasan, R.S. (Ramachandran Srini), Wang, Y.A. (Ying), Bergmann, S.M. (Sven), Vollenweider, P. (Peter), Waeber, G. (Gérard), Laitinen, J. (Jaana), Pouta, A. (Anneli), Zitting, P. (Paavo), McArdle, W.L. (Wendy), Kroemer, H.K. (Heyo), Völker, U. (Uwe), Völzke, H. (Henry), Glazer, N.L. (Nicole), Taylor, K.D. (Kent), Harris, T.B. (Tamara), Alavere, H. (Helene), Haller, T. (Toomas), Keis, A. (Aime), Tammesoo, M.L., Aulchenko, Y.S. (Yurii), Khaw, K-T. (Kay-Tee), Galan, P. (Pilar), Hercberg, S. (Serge), Lathrop, G.M. (Mark), Eyheramendy, S. (Susana), Org, E. (Elin), Sõber, S. (Siim), Lu, X. (Xiaowen), Nolte, I.M. (Ilja), Penninx, B.W.J.H. (Brenda), Corre, T. (Tanguy), Masciullo, C. (Corrado), Sala, C. (Cinzia), Groop, L. (Leif), Voight, B.F. (Benjamin), Melander, O. (Olle), O'Donnell, C.J. (Christopher), Salomaa, V. (Veikko), Adamo, P. (Pio) d', Fabretto, A. (Antonella), Faletra, F. (Flavio), Ulivi, S. (Shelia), Del Greco, F. (Fabiola), Facheris, M.F. (Maurizio), Collins, F.S. (Francis), Bergman, R.N. (Richard), Beilby, J.P. (John), Hung, J. (Judy), Musk, A.W. (Arthur), Mangino, M. (Massimo), Shin, S.Y. (So Youn), Soranzo, N. (Nicole), Watkins, H. (Hugh), Goel, A. (Anuj), Hamsten, A. (Anders), Gider, P. (Pierre), Loitfelder, M. (Marisa), Zeginigg, M. (Marion), Hernandez, D.G. (Dena), Najjar, S.S. (Samer), Navarro, P. (Pau), Wild, S.H. (Sarah), Corsi, A.M. (Anna Maria), Singleton, A. (Andrew), Geus, E.J.C. (Eco) de, Willemsen, G.A.H.M. (Gonneke), Parker, A.N. (Alex), Rose, L.M. (Lynda), Buckley, B.M. (Brendan M.), Stott, D.J. (David. J.), Orrù, M. (Marco), Uda, M. (Manuela), Klauw, M.M. (Melanie) van der, Scott, J. (James), Chen, Y.D.I. (Yii-Der Ida), Burke, G.L. (Greg), Kähönen, M. (Mika), Viikari, J. (Jorma), Döring, A. (Angela), Meitinger, T. (Thomas), Davis, G.S., Starr, J.M. (John), Emilsson, V. (Valur), Plump, A.S. (Andrew), Lindeman, J.H. (Jan H.), Hoen, P.A.C. (Peter) 't, König, I.R. (Inke), Felix, J.F. (Janine), Clarke, R., Hopewell, J., Ongen, H. (Halit), Breteler, M.M.B. (Monique), Debette, S. (Stéphanie), DeStefano, A.L. (Anita), Fornage, M. (Myriam), Mitchell, G.F. (Gary), Holm, H. (Hilma), Stefansson, K. (Kari), Thorleifsson, G. (Gudmar), Thorsteinsdottir, U. (Unnur), Samani, N.J. (Nilesh), Preuss, M. (Michael), Rudan, I. (Igor), Hayward, C. (Caroline), Deary, I.J. (Ian), Wichmann, H.E. (Heinz Erich), Raitakari, O. (Olli), Palmas, W. (Walter), Kooner, J.S. (Jaspal), Stolk, R.P. (Ronald), Jukema, J.W. (Jan Wouter), Wright, A.F. (Alan), Boomsma, D.I. (Dorret), Bandinelli, S. (Stefania), Gyllensten, U. (Ulf), Wilson, J.F. (James), Ferrucci, L. (Luigi), Farrall, M. (Martin), Spector, T.D. (Timothy), Palmer, L.J., Tuomilehto, J. (Jaakko), Pfeufer, A. (Arne), Gasparini, P. (Paolo), Siscovick, D.S. (David), Altshuler, D. (David), Loos, R.J.F. (Ruth), Toniolo, D. (Daniela), Snieder, H. (Harold), Gieger, C. (Christian), Meneton, P. (Pierre), Wareham, N.J. (Nick), Oostra, B.A. (Ben), Metspalu, A. (Andres), Launer, L.J. (Lenore), Rettig, R. (Rainer), Strachan, D.P. (David), Beckmann, J.S. (Jacques), Witteman, J.C.M. (Jacqueline), Willems van Dijk, J.A.P. (Ko), Boerwinkle, E.A. (Eric), Boehnke, M. (Michael), Ridker, P.M. (Paul), Järvelin, M.R., Chakravarti, A. (Aravinda), Erdmann, J. (Jeanette), Gudnason, V. (Vilmundur), Newton-Cheh, C. (Christopher), Levy, D. (Daniel), Arora, P. (Pankaj), Munroe, P. (Patricia), Psaty, B.M. (Bruce), Caulfield, M. (Mark), Li, X. (Xinzhong), Rao, D.C. (Dabeeru C.), Elliott, P. (Paul), Tikka-Kleemola, P. (Päivi), Abecasis, G.R. (Gonçalo), Barroso, I.E. (Inês), Wain, L.V. (Louise), Verwoert, G.C. (Germaine), O'Reilly, P.F. (Paul), Shi, G. (Gang), Johnson, T. (Toby), Bochud, M. (Murielle), Rice, K. (Kenneth), Henneman, P. (Peter), Smith, A.V. (Albert Vernon), Ehret, G.B. (Georg), Amin, N. (Najaf), Larson, M.G. (Martin), Mooser, V. (Vincent), Hadley, D. (David), Dörr, M. (Marcus), Bis, J.C. (Joshua), Aspelund, T. (Thor), Esko, T. (Tõnu), Janssens, A.C.J.W. (Cécile), Zhao, J.H. (Jing Hua), Heath, S.C. (Simon), Laan, M. (Maris), Fu, J. (Jingyuan), Pistis, G. (Giorgio), Luan, J., Lucas, G. (Gavin), Pirastu, N. (Nicola), Pichler, I. (Irene), Jackson, A.U. (Anne), Webster, R.J. (Rebecca J.), Zhang, F.F., Peden, J. (John), Schmidt, R. (Reinhold), Tanaka, T. (Toshiko), Campbell, H. (Harry), Igl, W. (Wilmar), Milaneschi, Y. (Yuri), Hottenga, J.J. (Jouke Jan), Vitart, V. (Veronique), Chasman, D.I. (Daniel), Trompet, S. (Stella), Bragg-Gresham, J.L. (Jennifer L.), Alizadeh, B.Z. (Behrooz), Chambers, J.C. (John), Guo, X. (Xiuqing), Lehtimäki, T. (Terho), Kuhnel, B. (Brigitte), Lopez, L.M., Polasek, O. (Ozren), Boban, M. (Mladen), Nelson, C.P. (Christopher P.), Morrison, A.C. (Alanna), Pihur, V. (Vasyl), Ganesh, S.K. (Santhi), Hofman, A. (Albert), Kundu, S. (Suman), Mattace Raso, F.U.S. (Francesco), Rivadeneira Ramirez, F. (Fernando), Sijbrands, E.J.G. (Eric), Uitterlinden, A.G. (André), Hwang, S.J., Vasan, R.S. (Ramachandran Srini), Wang, Y.A. (Ying), Bergmann, S.M. (Sven), Vollenweider, P. (Peter), Waeber, G. (Gérard), Laitinen, J. (Jaana), Pouta, A. (Anneli), Zitting, P. (Paavo), McArdle, W.L. (Wendy), Kroemer, H.K. (Heyo), Völker, U. (Uwe), Völzke, H. (Henry), Glazer, N.L. (Nicole), Taylor, K.D. (Kent), Harris, T.B. (Tamara), Alavere, H. (Helene), Haller, T. (Toomas), Keis, A. (Aime), Tammesoo, M.L., Aulchenko, Y.S. (Yurii), Khaw, K-T. (Kay-Tee), Galan, P. (Pilar), Hercberg, S. (Serge), Lathrop, G.M. (Mark), Eyheramendy, S. (Susana), Org, E. (Elin), Sõber, S. (Siim), Lu, X. (Xiaowen), Nolte, I.M. (Ilja), Penninx, B.W.J.H. (Brenda), Corre, T. (Tanguy), Masciullo, C. (Corrado), Sala, C. (Cinzia), Groop, L. (Leif), Voight, B.F. (Benjamin), Melander, O. (Olle), O'Donnell, C.J. (Christopher), Salomaa, V. (Veikko), Adamo, P. (Pio) d', Fabretto, A. (Antonella), Faletra, F. (Flavio), Ulivi, S. (Shelia), Del Greco, F. (Fabiola), Facheris, M.F. (Maurizio), Collins, F.S. (Francis), Bergman, R.N. (Richard), Beilby, J.P. (John), Hung, J. (Judy), Musk, A.W. (Arthur), Mangino, M. (Massimo), Shin, S.Y. (So Youn), Soranzo, N. (Nicole), Watkins, H. (Hugh), Goel, A. (Anuj), Hamsten, A. (Anders), Gider, P. (Pierre), Loitfelder, M. (Marisa), Zeginigg, M. (Marion), Hernandez, D.G. (Dena), Najjar, S.S. (Samer), Navarro, P. (Pau), Wild, S.H. (Sarah), Corsi, A.M. (Anna Maria), Singleton, A. (Andrew), Geus, E.J.C. (Eco) de, Willemsen, G.A.H.M. (Gonneke), Parker, A.N. (Alex), Rose, L.M. (Lynda), Buckley, B.M. (Brendan M.), Stott, D.J. (David. J.), Orrù, M. (Marco), Uda, M. (Manuela), Klauw, M.M. (Melanie) van der, Scott, J. (James), Chen, Y.D.I. (Yii-Der Ida), Burke, G.L. (Greg), Kähönen, M. (Mika), Viikari, J. (Jorma), Döring, A. (Angela), Meitinger, T. (Thomas), Davis, G.S., Starr, J.M. (John), Emilsson, V. (Valur), Plump, A.S. (Andrew), Lindeman, J.H. (Jan H.), Hoen, P.A.C. (Peter) 't, König, I.R. (Inke), Felix, J.F. (Janine), Clarke, R., Hopewell, J., Ongen, H. (Halit), Breteler, M.M.B. (Monique), Debette, S. (Stéphanie), DeStefano, A.L. (Anita), Fornage, M. (Myriam), Mitchell, G.F. (Gary), Holm, H. (Hilma), Stefansson, K. (Kari), Thorleifsson, G. (Gudmar), Thorsteinsdottir, U. (Unnur), Samani, N.J. (Nilesh), Preuss, M. (Michael), Rudan, I. (Igor), Hayward, C. (Caroline), Deary, I.J. (Ian), Wichmann, H.E. (Heinz Erich), Raitakari, O. (Olli), Palmas, W. (Walter), Kooner, J.S. (Jaspal), Stolk, R.P. (Ronald), Jukema, J.W. (Jan Wouter), Wright, A.F. (Alan), Boomsma, D.I. (Dorret), Bandinelli, S. (Stefania), Gyllensten, U. (Ulf), Wilson, J.F. (James), Ferrucci, L. (Luigi), Farrall, M. (Martin), Spector, T.D. (Timothy), Palmer, L.J., Tuomilehto, J. (Jaakko), Pfeufer, A. (Arne), Gasparini, P. (Paolo), Siscovick, D.S. (David), Altshuler, D. (David), Loos, R.J.F. (Ruth), Toniolo, D. (Daniela), Snieder, H. (Harold), Gieger, C. (Christian), Meneton, P. (Pierre), Wareham, N.J. (Nick), Oostra, B.A. (Ben), Metspalu, A. (Andres), Launer, L.J. (Lenore), Rettig, R. (Rainer), Strachan, D.P. (David), Beckmann, J.S. (Jacques), Witteman, J.C.M. (Jacqueline), Willems van Dijk, J.A.P. (Ko), Boerwinkle, E.A. (Eric), Boehnke, M. (Michael), Ridker, P.M. (Paul), Järvelin, M.R., Chakravarti, A. (Aravinda), Erdmann, J. (Jeanette), Gudnason, V. (Vilmundur), Newton-Cheh, C. (Christopher), Levy, D. (Daniel), Arora, P. (Pankaj), Munroe, P. (Patricia), Psaty, B.M. (Bruce), Caulfield, M. (Mark), Li, X. (Xinzhong), Rao, D.C. (Dabeeru C.), Elliott, P. (Paul), Tikka-Kleemola, P. (Päivi), Abecasis, G.R. (Gonçalo), and Barroso, I.E. (Inês)

Abstract

Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans. We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we identified at genome-wide significance (P = 2.7 × 10 -8 to P = 2.3 × 10 -13) four new PP loci (at 4q12 near CHIC2, 7q22.3 near PIK3CG, 8q24.12 in NOV and 11q24.3 near ADAMTS8), two new MAP loci (3p21.31 in MAP4 and 10q25.3 near ADRB1) and one locus associated with both of these traits (2q24.3 near FIGN) that has also recently been associated with SBP in east Asians. For three of the new PP loci, the estimated effect for SBP was opposite of that for DBP, in contrast to the majority of common SBP- and DBP-associated variants, which show concordant effects on both traits. These findings suggest new genetic pathways underlying blood pressure variation, some of which may differentially influence SBP and DBP.

Published
2011
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39. Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk

Author

Ehret, G.B. (Georg), Munroe, P. (Patricia), Rice, K.M. (Kenneth), Bochud, M. (Murielle), Johnson, A.D. (Andrew), Chasman, D.I. (Daniel), Smith, A.V. (Albert Vernon), Tobin, M.D. (Martin), Verwoert, G.C. (Germaine), Hwang, S.J., Pihur, V. (Vasyl), Vollenweider, P. (Peter), O'Reilly, P.F. (Paul), Amin, N. (Najaf), Bragg-Gresham, J.L. (Jennifer L.), Teumer, A. (Alexander), Glazer, N.L. (Nicole), Launer, L.J. (Lenore), Zhao, J.H. (Jing Hua), Aulchenko, Y.S. (Yurii), Heath, S.C. (Simon), Sõber, S. (Siim), Parsa, A. (Afshin), Luan, J., Arora, P. (Pankaj), Dehghan, A. (Abbas), Zhang, F. (Feng), Lucas, G. (Gavin), Hicks, A.A. (Andrew), Jackson, A.U. (Anne), Peden, J. (John), Tanaka, T. (Toshiko), Wild, S.H. (Sarah), Rudan, I. (Igor), Igl, W. (Wilmar), Milaneschi, Y. (Yuri), Parker, A.N. (Alex), Fava, C. (Cristiano), Chambers, J.C. (John), Fox, E.R. (Ervin), Kumari, M. (Meena), Jin Go, M. (Min), Harst, P. (Pim) van der, Kao, W.-H.L. (Wen-Hong Linda), Sjögren, M. (Marketa), Vinay, D.G., Alexander, M. (Myriam), Tabara, Y. (Yasuharu), Shaw-Hawkins, S. (Sue), Whincup, P.H. (Peter), Liu, Y. (YongMei), Shi, G. (Gang), Kuusisto, J. (Johanna), Tayo, B. (Bamidele), Seielstad, M. (Mark), Sim, X. (Xueling), Hoang Nguyen, K.-D., Lehtimäki, T. (Terho), Matullo, G. (Giuseppe), Wu, Y. (Ying), Gaunt, T.R. (Tom), Onland-Moret, N.C. (Charlotte), Cooper, M.N. (Matthew), Platou, C. (Carl), Org, E. (Elin), Hardy, R. (Rebecca), Dahgam, S. (Santosh), Palmen, J. (Jutta), Vitart, V. (Veronique), Braund, P.S. (Peter), Kuznetsova, T. (Tatiana), Uiterwaal, C.S.P.M. (Cuno), Adeyemo, A. (Adebowale), Palmas, W. (Walter), Campbell, H. (Harry), Ludwig, B. (Barbara), Tomaszewski, M., Tzoulaki, I., Palmer, N.D. (Nicholette), Aspelund, T. (Thor), Garcia, M. (Melissa), Chang, Y.-P.C. (Yen-Pei), O´Connell, J.R., Steinle, N.I. (Nanette), Grobbee, D.E. (Diederick), Arking, D.E. (Dan), Kardia, S.L. (Sharon), Morrison, A.C. (Alanna), Hernandez, D.G. (Dena), Najjar, S.S. (Samer), McArdle, W.L. (Wendy), Hadley, D. (David), Brown, M.J. (Morris), Connell, J. (John), Hingorani, A. (Aroon), Day, I.N.M. (Ian), Lawlor, D.A. (Debbie), Beilby, J.P. (John), Lawrence, R.W. (Robert), Clarke, R., Hopewell, J., Ongen, H. (Halit), Dreisbach, A.W. (Albert), Li, Y. (Yali), Hunter Young, J., Bis, J.C. (Joshua), Kähönen, M. (Mika), Viikari, J. (Jorma), Lee, N.R. (Nanette), Chen, M-H. (Ming-Huei), Olden, M. (Matthias), Pattaro, C. (Cristian), Hoffman Bolton, J.A. (Judith), Köttgen, A. (Anna), Bergmann, S.M. (Sven), Mooser, V. (Vincent), Chaturvedi, N. (Nish), Frayling, T.M. (Timothy), Islam, M. (Muhammad), Jafar, T.H. (Tazeen), Kulkarni, S.R. (Smita), Bornstein, S.R. (Stefan), Gräßler, J. (Jürgen), Groop, L. (Leif), Voight, B.F. (Benjamin), Kettunen, J. (Johannes), Howard, P. (Philip), Taylor, A. (Andrew), Guarrera, S. (Simonetta), Ricceri, F. (Fulvio), Emilsson, V. (Valur), Plump, A.S. (Andrew), Khaw, K-T. (Kay-Tee), Weder, A.B. (Alan), Hunt, S.C. (Steven), Sun, Y.V. (Yan), Bergman, R.N. (Richard), Collins, F.S. (Francis), Bonnycastle, L.L. (Lori), Scott, L.J. (Laura), Stringham, H.M. (Heather), Peltonen, L. (Leena Johanna), Perola, M. (Markus), Vartiainen, E. (Erkki), Brand, S.-M., Staessen, J.A. (Jan), Wang, Y.A. (Ying), Burton, P.R. (Paul), Soler Artigas, M. (Maria), Dong, Y. (Yanbin), Snieder, H. (Harold), Zhu, H. (Haidong), Lohman, K. (Kurt), Rudock, M.E. (Megan), Heckbert, S.R. (Susan), Wiggins, K.L. (Kerri), Doumatey, A. (Ayo), Shriner, D. (Daniel), Veldre, G. (Gudrun), Viigimaa, M. (Margus), Kinra, S. (Sanjay), Prabhakaran, D. (Dorairaj), Tripathy, V. (Vikal), Langefeld, C.D. (Carl), Rosengren, A. (Annika), Thelle, D.S. (Dag), Corsi, A.M. (Anna Maria), Singleton, A. (Andrew), Forrester, T. (Terrence), Hilton, G. (Gina), McKenzie, C.A. (Colin), Salako, T. (Tunde), Iwai, N. (Naoharu), Kita, Y. (Yoshikuni), Ogihara, T. (Toshio), Ohkubo, T. (Takayoshi), Okamura, T. (Tomonori), Ueshima, H. (Hirotsugu), Umemura, S. (Satoshi), Eyheramendy, S. (Susana), Meitinger, T. (Thomas), Wichmann, H.E. (Heinz Erich), Shin Cho, Y. (Yoon), Kim, H.-L., Sehmi, J.S. (Joban), Hedblad, B. (Bo), Nilsson, P. (Peter), Davey-Smith, G. (George), Wong, A. (Andrew), Narisu, N. (Narisu), Stancáková, A. (Alena), Raffel, L.J. (Leslie), Yao, J. (Jie), Kathiresan, S. (Sekar), O'Donnell, C.J. (Christopher), Schwartz, S.M. (Stephen), Ikram, M.A. (Arfan), Longstreth Jr, W.T., Mosley, T.H. (Thomas), Seshadri, S. (Sudha), Shrine, N.R.G. (Nick), Wain, L.V. (Louise), Morken, M.A. (Mario), Swift, A.J. (Amy), Laitinen, J. (Jaana), Prokopenko, I. (Inga), Zitting, P. (Paavo), Humphries, S.E. (Steve), Danesh, J. (John), Rasheed, A. (Asif), Goel, A. (Anuj), Hamsten, A. (Anders), Watkins, H. (Hugh), Gilst, W.H. (Wiek) van, Janipalli, C.S. (Charles), Radha Mani, K., Yajnik, C. (Chittaranjan), Hofman, A. (Albert), Mattace Raso, F.U.S. (Francesco), Oostra, B.A. (Ben), Demirkan, A. (Ayşe), Isaacs, A.J. (Aaron), Rivadeneira Ramirez, F. (Fernando), Lakatta, E. (Edward), Orrù, M. (Marco), Scuteri, A. (Angelo), Ala-Korpela, M. (Mika), Kangas, A.J. (Antti), Lyytikäinen, L.-P. (Leo-Pekka), Soininen, P. (Pasi), Tukiainen, T. (Taru), Würtz, P. (Peter), Twee-Hee Ong, R. (Rick), Dörr, M. (Marcus), Kroemer, H.K. (Heyo), Völker, U. (Uwe), Völzke, H. (Henry), Galan, P. (Pilar), Hercberg, S. (Serge), Lathrop, G.M. (Mark), Zelenika, D. (Diana), Deloukas, P. (Panagiotis), Mangino, M. (Massimo), Spector, T.D. (Timothy), Zhai, G. (Guangju), Meschia, J.F. (James F.), Nalls, M.A. (Michael), Sharma, P. (Pankaj), Terzic, J. (Janos), Kranthi Kumar, M.V., Denniff, M. (Matthew), Zukowska-Szczechowska, E. (Ewa), Wagenknecht, L.E. (Lynne), Fowkes, F.G.R. (Gerald), Charchar, F.J. (Fadi), Schwarz, P.E.H. (Peter), Hayward, C. (Caroline), Guo, X. (Xiuqing), Rotimi, C. (Charles), Bots, M.L. (Michiel), Samani, N.J. (Nilesh), Polasek, O. (Ozren), Talmud, P.J. (Philippa), Nyberg, F. (Fredrik), Kuh, D. (Diana), Laan, M. (Maris), Hveem, K. (Kristian), Schouw, Y.T. (Yvonne) van der, Casas, J.P. (Juan), Mohlke, K.L. (Karen), Vineis, P. (Paolo), Raitakari, O. (Olli), Ganesh, S.K. (Santhi), Shyong Tai, E., Laakso, M. (Markku), Rao, D.C. (Dabeeru C.), Harris, T.B. (Tamara), Morris, R.W. (Richard), Dominiczak, A. (Anna), Kivimaki, M. (Mika), Marmot, M. (Michael), Miki, T. (Tetsuro), Saleheen, D., Chandak, G.R. (Giriraj), Coresh, J. (Josef), Navis, G. (Gerjan), Salomaa, V. (Veikko), Han, B.-G., Kooner, J.S. (Jaspal), Melander, O. (Olle), Ridker, P.M. (Paul), Bandinelli, S. (Stefania), Gyllensten, U. (Ulf), Wright, A.F. (Alan), Wilson, J.F. (James), Ferrucci, L. (Luigi), Farrall, M. (Martin), Tuomilehto, J. (Jaakko), Pramstaller, P.P. (Peter Paul), Elosua, R. (Roberto), Soranzo, N. (Nicole), Sijbrands, E.J.G. (Eric), Altshuler, D. (David), Loos, R.J.F. (Ruth), Shuldiner, A.R. (Alan), Gieger, C. (Christian), Meneton, P. (Pierre), Uitterlinden, A.G. (André), Wareham, N.J. (Nick), Gudnason, V. (Vilmundur), Rotter, J.I. (Jerome), Rettig, R. (Rainer), Uda, M. (Manuela), Strachan, D.P. (David), Witteman, J.C.M. (Jacqueline), Hartikainen, A.L., Beckmann, J.S. (Jacques), Boerwinkle, E.A. (Eric), Erdmann, J. (Jeanette), Vasan, R.S. (Ramachandran Srini), Boehnke, M. (Michael), Larson, M.G. (Martin), Järvelin, M.R., Psaty, B.M. (Bruce), Tikka-Kleemola, P. (Päivi), Newton-Cheh, C. (Christopher), Elliott, P. (Paul), Levy, D. (Daniel), Caulfield, M. (Mark), Abecasis, G.R. (Gonçalo), Adair, L.S. (Linda), Bakker, S.J.L. (Stephan), Barroso, I.E. (Inês), Ehret, G.B. (Georg), Munroe, P. (Patricia), Rice, K.M. (Kenneth), Bochud, M. (Murielle), Johnson, A.D. (Andrew), Chasman, D.I. (Daniel), Smith, A.V. (Albert Vernon), Tobin, M.D. (Martin), Verwoert, G.C. (Germaine), Hwang, S.J., Pihur, V. (Vasyl), Vollenweider, P. (Peter), O'Reilly, P.F. (Paul), Amin, N. (Najaf), Bragg-Gresham, J.L. (Jennifer L.), Teumer, A. (Alexander), Glazer, N.L. (Nicole), Launer, L.J. (Lenore), Zhao, J.H. (Jing Hua), Aulchenko, Y.S. (Yurii), Heath, S.C. (Simon), Sõber, S. (Siim), Parsa, A. (Afshin), Luan, J., Arora, P. (Pankaj), Dehghan, A. (Abbas), Zhang, F. (Feng), Lucas, G. (Gavin), Hicks, A.A. (Andrew), Jackson, A.U. (Anne), Peden, J. (John), Tanaka, T. (Toshiko), Wild, S.H. (Sarah), Rudan, I. (Igor), Igl, W. (Wilmar), Milaneschi, Y. (Yuri), Parker, A.N. (Alex), Fava, C. (Cristiano), Chambers, J.C. (John), Fox, E.R. (Ervin), Kumari, M. (Meena), Jin Go, M. (Min), Harst, P. (Pim) van der, Kao, W.-H.L. (Wen-Hong Linda), Sjögren, M. (Marketa), Vinay, D.G., Alexander, M. (Myriam), Tabara, Y. (Yasuharu), Shaw-Hawkins, S. (Sue), Whincup, P.H. (Peter), Liu, Y. (YongMei), Shi, G. (Gang), Kuusisto, J. (Johanna), Tayo, B. (Bamidele), Seielstad, M. (Mark), Sim, X. (Xueling), Hoang Nguyen, K.-D., Lehtimäki, T. (Terho), Matullo, G. (Giuseppe), Wu, Y. (Ying), Gaunt, T.R. (Tom), Onland-Moret, N.C. (Charlotte), Cooper, M.N. (Matthew), Platou, C. (Carl), Org, E. (Elin), Hardy, R. (Rebecca), Dahgam, S. (Santosh), Palmen, J. (Jutta), Vitart, V. (Veronique), Braund, P.S. (Peter), Kuznetsova, T. (Tatiana), Uiterwaal, C.S.P.M. (Cuno), Adeyemo, A. (Adebowale), Palmas, W. (Walter), Campbell, H. (Harry), Ludwig, B. (Barbara), Tomaszewski, M., Tzoulaki, I., Palmer, N.D. (Nicholette), Aspelund, T. (Thor), Garcia, M. (Melissa), Chang, Y.-P.C. (Yen-Pei), O´Connell, J.R., Steinle, N.I. (Nanette), Grobbee, D.E. (Diederick), Arking, D.E. (Dan), Kardia, S.L. (Sharon), Morrison, A.C. (Alanna), Hernandez, D.G. (Dena), Najjar, S.S. (Samer), McArdle, W.L. (Wendy), Hadley, D. (David), Brown, M.J. (Morris), Connell, J. (John), Hingorani, A. (Aroon), Day, I.N.M. (Ian), Lawlor, D.A. (Debbie), Beilby, J.P. (John), Lawrence, R.W. (Robert), Clarke, R., Hopewell, J., Ongen, H. (Halit), Dreisbach, A.W. (Albert), Li, Y. (Yali), Hunter Young, J., Bis, J.C. (Joshua), Kähönen, M. (Mika), Viikari, J. (Jorma), Lee, N.R. (Nanette), Chen, M-H. (Ming-Huei), Olden, M. (Matthias), Pattaro, C. (Cristian), Hoffman Bolton, J.A. (Judith), Köttgen, A. (Anna), Bergmann, S.M. (Sven), Mooser, V. (Vincent), Chaturvedi, N. (Nish), Frayling, T.M. (Timothy), Islam, M. (Muhammad), Jafar, T.H. (Tazeen), Kulkarni, S.R. (Smita), Bornstein, S.R. (Stefan), Gräßler, J. (Jürgen), Groop, L. (Leif), Voight, B.F. (Benjamin), Kettunen, J. (Johannes), Howard, P. (Philip), Taylor, A. (Andrew), Guarrera, S. (Simonetta), Ricceri, F. (Fulvio), Emilsson, V. (Valur), Plump, A.S. (Andrew), Khaw, K-T. (Kay-Tee), Weder, A.B. (Alan), Hunt, S.C. (Steven), Sun, Y.V. (Yan), Bergman, R.N. (Richard), Collins, F.S. (Francis), Bonnycastle, L.L. (Lori), Scott, L.J. (Laura), Stringham, H.M. (Heather), Peltonen, L. (Leena Johanna), Perola, M. (Markus), Vartiainen, E. (Erkki), Brand, S.-M., Staessen, J.A. (Jan), Wang, Y.A. (Ying), Burton, P.R. (Paul), Soler Artigas, M. (Maria), Dong, Y. (Yanbin), Snieder, H. (Harold), Zhu, H. (Haidong), Lohman, K. (Kurt), Rudock, M.E. (Megan), Heckbert, S.R. (Susan), Wiggins, K.L. (Kerri), Doumatey, A. (Ayo), Shriner, D. (Daniel), Veldre, G. (Gudrun), Viigimaa, M. (Margus), Kinra, S. (Sanjay), Prabhakaran, D. (Dorairaj), Tripathy, V. (Vikal), Langefeld, C.D. (Carl), Rosengren, A. (Annika), Thelle, D.S. (Dag), Corsi, A.M. (Anna Maria), Singleton, A. (Andrew), Forrester, T. (Terrence), Hilton, G. (Gina), McKenzie, C.A. (Colin), Salako, T. (Tunde), Iwai, N. (Naoharu), Kita, Y. (Yoshikuni), Ogihara, T. (Toshio), Ohkubo, T. (Takayoshi), Okamura, T. (Tomonori), Ueshima, H. (Hirotsugu), Umemura, S. (Satoshi), Eyheramendy, S. (Susana), Meitinger, T. (Thomas), Wichmann, H.E. (Heinz Erich), Shin Cho, Y. (Yoon), Kim, H.-L., Sehmi, J.S. (Joban), Hedblad, B. (Bo), Nilsson, P. (Peter), Davey-Smith, G. (George), Wong, A. (Andrew), Narisu, N. (Narisu), Stancáková, A. (Alena), Raffel, L.J. (Leslie), Yao, J. (Jie), Kathiresan, S. (Sekar), O'Donnell, C.J. (Christopher), Schwartz, S.M. (Stephen), Ikram, M.A. (Arfan), Longstreth Jr, W.T., Mosley, T.H. (Thomas), Seshadri, S. (Sudha), Shrine, N.R.G. (Nick), Wain, L.V. (Louise), Morken, M.A. (Mario), Swift, A.J. (Amy), Laitinen, J. (Jaana), Prokopenko, I. (Inga), Zitting, P. (Paavo), Humphries, S.E. (Steve), Danesh, J. (John), Rasheed, A. (Asif), Goel, A. (Anuj), Hamsten, A. (Anders), Watkins, H. (Hugh), Gilst, W.H. (Wiek) van, Janipalli, C.S. (Charles), Radha Mani, K., Yajnik, C. (Chittaranjan), Hofman, A. (Albert), Mattace Raso, F.U.S. (Francesco), Oostra, B.A. (Ben), Demirkan, A. (Ayşe), Isaacs, A.J. (Aaron), Rivadeneira Ramirez, F. (Fernando), Lakatta, E. (Edward), Orrù, M. (Marco), Scuteri, A. (Angelo), Ala-Korpela, M. (Mika), Kangas, A.J. (Antti), Lyytikäinen, L.-P. (Leo-Pekka), Soininen, P. (Pasi), Tukiainen, T. (Taru), Würtz, P. (Peter), Twee-Hee Ong, R. (Rick), Dörr, M. (Marcus), Kroemer, H.K. (Heyo), Völker, U. (Uwe), Völzke, H. (Henry), Galan, P. (Pilar), Hercberg, S. (Serge), Lathrop, G.M. (Mark), Zelenika, D. (Diana), Deloukas, P. (Panagiotis), Mangino, M. (Massimo), Spector, T.D. (Timothy), Zhai, G. (Guangju), Meschia, J.F. (James F.), Nalls, M.A. (Michael), Sharma, P. (Pankaj), Terzic, J. (Janos), Kranthi Kumar, M.V., Denniff, M. (Matthew), Zukowska-Szczechowska, E. (Ewa), Wagenknecht, L.E. (Lynne), Fowkes, F.G.R. (Gerald), Charchar, F.J. (Fadi), Schwarz, P.E.H. (Peter), Hayward, C. (Caroline), Guo, X. (Xiuqing), Rotimi, C. (Charles), Bots, M.L. (Michiel), Samani, N.J. (Nilesh), Polasek, O. (Ozren), Talmud, P.J. (Philippa), Nyberg, F. (Fredrik), Kuh, D. (Diana), Laan, M. (Maris), Hveem, K. (Kristian), Schouw, Y.T. (Yvonne) van der, Casas, J.P. (Juan), Mohlke, K.L. (Karen), Vineis, P. (Paolo), Raitakari, O. (Olli), Ganesh, S.K. (Santhi), Shyong Tai, E., Laakso, M. (Markku), Rao, D.C. (Dabeeru C.), Harris, T.B. (Tamara), Morris, R.W. (Richard), Dominiczak, A. (Anna), Kivimaki, M. (Mika), Marmot, M. (Michael), Miki, T. (Tetsuro), Saleheen, D., Chandak, G.R. (Giriraj), Coresh, J. (Josef), Navis, G. (Gerjan), Salomaa, V. (Veikko), Han, B.-G., Kooner, J.S. (Jaspal), Melander, O. (Olle), Ridker, P.M. (Paul), Bandinelli, S. (Stefania), Gyllensten, U. (Ulf), Wright, A.F. (Alan), Wilson, J.F. (James), Ferrucci, L. (Luigi), Farrall, M. (Martin), Tuomilehto, J. (Jaakko), Pramstaller, P.P. (Peter Paul), Elosua, R. (Roberto), Soranzo, N. (Nicole), Sijbrands, E.J.G. (Eric), Altshuler, D. (David), Loos, R.J.F. (Ruth), Shuldiner, A.R. (Alan), Gieger, C. (Christian), Meneton, P. (Pierre), Uitterlinden, A.G. (André), Wareham, N.J. (Nick), Gudnason, V. (Vilmundur), Rotter, J.I. (Jerome), Rettig, R. (Rainer), Uda, M. (Manuela), Strachan, D.P. (David), Witteman, J.C.M. (Jacqueline), Hartikainen, A.L., Beckmann, J.S. (Jacques), Boerwinkle, E.A. (Eric), Erdmann, J. (Jeanette), Vasan, R.S. (Ramachandran Srini), Boehnke, M. (Michael), Larson, M.G. (Martin), Järvelin, M.R., Psaty, B.M. (Bruce), Tikka-Kleemola, P. (Päivi), Newton-Cheh, C. (Christopher), Elliott, P. (Paul), Levy, D. (Daniel), Caulfield, M. (Mark), Abecasis, G.R. (Gonçalo), Adair, L.S. (Linda), Bakker, S.J.L. (Stephan), and Barroso, I.E. (Inês)

Abstract

Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140mmg Hg systolic blood pressure ≥90mmg Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3 GUCY1B3, NPR3 C5orf23, ADM, FURIN FES, GOSR2, GNAS EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 geno

Published
2011
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40. Age-specific success rate for women undertaking their first assisted reproduction technology treatment using their own oocytes in Australia, 2002-2005.

Author

Black D., Wang Y.A., Sullivan E.A., Healy D., Black D., Wang Y.A., Sullivan E.A., and Healy D.

Abstract

BACKGROUND: Woman's age is an independent factor determining the success of assisted reproductive technology treatment. This study presents the age-specific success rate of first autologous fresh treatment in Australia during 2002-2005. METHOD(S): This is a retrospective population-based study of 36 412 initiated first autologous fresh cycles conducted in Australian clinics during 2002-2005. Pregnancy and live delivery rates per initiated cycle were determined for each age. RESULT(S): The overall live delivery rate per initiated cycle was 20.4% with the highest success rate in women aged between 22 and 36 years. Male factor only infertility had a higher live delivery rate (22.0%) than female factor only infertility (19.2%). Advancing woman's age was associated with a decline in success rate. For women >=30 years, each additional 1 year in age was associated with an 11% (99% CI: 10-12%) reduction in the chance of achieving pregnancy and a 13% (99% CI: 12-14%) reduction in the chance of a live delivery. If women aged 35 years or older would have had their first autologous fresh treatment 1 year earlier, 15% extra live deliveries would be expected. CONCLUSION(S): This study suggested that women aged 35 years or older should be encouraged to seek early fertility assessment and treatment where clinically indicated. © The Author 2008. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.

Published
2008

45. Numerical Investigation on the Relationship between Human Thermal Comfort and Thermal Balance under Radiant Cooling System.

Author

Gao, S., Wang, Y.A., Zhang, S.M., Zhao, M., Meng, X.Z., Zhang, L.Y., Yang, C., and Jin, L.W.

Abstract

The radiant air conditioning system, possessing the characteristics of draft less and small temperature gradients in the occupied zone, is becoming increasingly attractive in recent years, due to its advantage of providing more comfortable indoor environment with low energy consumption against the conventional convective air conditioning system. In order to master the features of the radiant air conditioning system and improve its design process, the interrelation among the human thermal comfort and the heat exchange between human body and its surroundings subject to the radiant air conditioning system is investigated in this paper. Based on Fanger's thermal comfort model, the PMV (Predicted Mean Vote) is used to evaluate the human thermal comfort. To calculate the heat loss from human body, the human thermal balance and heat release characteristics under radiant cooling system are discussed in detail. The CFD model in terms of different cooling ceiling temperatures and air supply temperatures is simulated and analyzed by Airpak . The relationship between the heat loss from human body and thermal comfort is achieved based on the simplified formula for the heat loss and the PMV value obtained from numerical results. For human body under radiant air conditioning system, numerical results showed that the sensible heat loss from human body is approximately linear to the PMV under all simulated conditions. The simplified PMV model, directly from the respect of human heat balance instead of complicated environmental parameters, is finally proposed. [ABSTRACT FROM AUTHOR]

Published
2016
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50. Pten and p53 Converge on c-Myc to Control Differentiation, Self-renewal, and Transformation of Normal and Neoplastic Stem Cells in Glioblastoma

Author

Zheng, H., primary, Ying, H., additional, Yan, H., additional, Kimmelman, A.C., additional, Hiller, D.J., additional, Chen, A.-J., additional, Perry, S.R., additional, Tonon, G., additional, Chu, G.C., additional, Ding, Z., additional, Stommel, J.M., additional, Dunn, K.L., additional, Wiedemeyer, R., additional, You, M.J., additional, Brennan, C., additional, Wang, Y.A., additional, Ligon, K.L., additional, Wong, W.H., additional, Chin, L., additional, and DePinho, R.A., additional

Published
2008
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