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16 results on '"Rosendaal, F.R. (Frits)"'

1. Rosuvastatin use reduces thrombin generation potential in patients with venous thromboembolism: a randomized controlled trial

Author

Orsi, F.A., Biedermann, J.S. (Joseph), Kruip, M.J.H.A. (Marieke), van der Meer, FJ, Rosendaal, F.R. (Frits), Vlieg, AV, Bos, M.H.A., Leebeek, F.W.G. (Frank), Cannegieter, S.C. (Suzanne), Lijfering, WM, Orsi, F.A., Biedermann, J.S. (Joseph), Kruip, M.J.H.A. (Marieke), van der Meer, FJ, Rosendaal, F.R. (Frits), Vlieg, AV, Bos, M.H.A., Leebeek, F.W.G. (Frank), Cannegieter, S.C. (Suzanne), and Lijfering, WM

Abstract

Background Statin therapy could form an alternative prophylactic treatment for venous thromboembolism (VTE) if statins are proven to downregulate hemostasis and prevent recurrent VTE, without increasing bleeding risk. Objectives The STAtins Reduce Thrombophilia (START) trial investigated whether statin affects coagulation in patients with prior VTE. Patients/methods After anticoagulation withdrawal, patients were randomized to rosuvastatin 20 mg day−1 for 4 weeks or no intervention. Plasma samples taken at baseline and at the end of the study were analyzed employing thrombin generation assay. Results and conclusions The study comprised 126 rosuvastatin users and 119 non‐users. Mean age was 58 years, 61% were men, 49% had unprovoked VTE and 75% had cardiovascular (CV) risk factors. Endogenous thrombin potential (ETP) increased from baseline to end of study in non‐statin users (mean 97.22 nm*min; 95% CI, 40.92–153.53) and decreased in rosuvastatin users (mean −24.94 nm*min; 95% CI, −71.81 to 21.93). The mean difference in ETP change between treatments was −120.24 nm*min (95% CI, −192.97 to −47.51), yielding a 10.4% ETP reduction by rosuvastatin. The thrombin peak increased in both non‐statin (mean 20.69 nm; 95% CI, 9.80–31.58) and rosuvastatin users (mean 8.41 nm; 95% CI −0.86 to 17.69). The mean difference in peak change between treatments was −11.88 nm (95% CI, −26.11 to 2.35), yielding a 5% peak reduction by rosuvastatin. Other thrombin generation parameters did not change substantially. The reduction in ETP and peak by rosuvastatin was more pronounced in the subgroups of participants with CV risk factors and with unprovoked VTE. We conclude that rosuvastatin reduces thrombin generation potential in patients who had VTE.

Published
2019
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2. Multiethnic meta-analysis identifies ancestry-specific and cross-ancestry loci for pulmonary function

Author

Wyss, A.B. (Annah B.), Sofer, T. (Tamar), Lee, M.K. (Mi Kyeong), Terzikhan, N. (Natalie), Nguyen, J.N. (Jennifer N.), Lahousse, L. (Lies), Latourelle, J.C. (Jeanne), Smith, A.V. (Albert), Bartz, T.M. (Traci M.), Feitosa, M.F. (Mary Furlan), Gao, W. (Wei), Ahluwalia, T.S. (Tarunveer Singh), Tang, W. (Wenbo), Oldmeadow, C. (Christopher), Duan, Q. (Qing), Jong, K. (Kim) de, Wojczynski, M.K. (Mary ), Wang, X.-Q. (Xin-Qun), Noordam, R. (Raymond), Hartwig, F.P. (Fernando Pires), Jackson, V.E. (Victoria E.), Wang, T. (Tianyuan), Obeidat, M. (Ma’en), Hobbs, B.D. (Brian D.), Huan, T. (Tianxiao), Gui, H. (Hongsheng), Parker, M.M. (Margaret M.), Hu, D. (Donglei), Mogil, L.S. (Lauren S.), Kichaev, G. (Gleb), Jin, J. (Jianping), Graff, M.J. (Maud J.L.), Harris, T.B. (Tamara), Kalhan, R. (Ravi), Heckbert, S.R. (Susan), Paternoster, L. (Lavinia), Burkart, K.M. (Kristin), Liu, Y. (YongMei), Holliday, E.G. (Elizabeth), Wilson, J.F. (James), Vonk, J.M. (Judith), Sanders, J.L. (Jason L.), Barr, R.G. (Graham), Mutsert, R. (Reneé) de, Menezes, A.M.B. (Ana Maria Baptista), Adams, H.H.H. (Hieab), Van Den Berge, M. (Maarten), Joehanes, R. (Roby), Levin, A.M. (Albert M.), Liberto, J. (Jennifer), Launer, L.J. (Lenore), Morrison, A.C. (Alanna), Sitlani, C.M. (Colleen), Celedón, J.C. (Juan C.), Kritchevsky, S.B. (Stephen), Scott, R.J. (Rodney J.), Christensen, K. (Kaare), Rotter, J.I. (Jerome I.), Bonten, T.N. (Tobias N.), Wehrmeister, F.C. (Fernando C.), Bossé, Y. (Yohan), Xiao, S. (Shujie), Oh, S. (Sam), Franceschini, N. (Nora), Brody, J.A. (Jennifer A.), Kaplan, R.C. (Robert), Lohman, K. (Kurt), McEvoy, M. (Mark), Province, M.A. (Mike), Rosendaal, F.R. (Frits), Taylor, K.D. (Kent), Nickle, D.C. (David C.), Williams, L.K. (L. Keoki), Burchard, E.G. (Esteban), Wheeler, H.E. (Heather), Sin, D.D. (Don D.), Gudnason, V. (Vilmundur), North, K.E. (Kari), Fornage, M. (Myriam), Psaty, B.M. (Bruce M.), Myers, R.H. (Richard), O’Connor, G. (George), Hansen, T. (Torben), Laurie, C.C. (Cathy C.), Cassano, P.A. (Patricia), Sung, J. (Joohon), Kim, W.J. (Woo Jin), Attia, J. (John), Lange, L.A. (Leslie), Boezen, H.M. (Marike), Thyagarajan, B. (Bharat), Rich, S.S. (Stephen), Mook-Kanamori, D.O. (Dennis O.), Horta, B.L. (Bernardo Lessa), Uitterlinden, A.G. (André), Im, H.K. (Hae Kyung), Cho, M.H. (Michael H.), Brusselle, G.G. (Guy), Gharib, S.A. (Sina), Dupuis, J. (Josée), Manichaikul, A. (Ani), London, S.J. (Stephanie J.), Wyss, A.B. (Annah B.), Sofer, T. (Tamar), Lee, M.K. (Mi Kyeong), Terzikhan, N. (Natalie), Nguyen, J.N. (Jennifer N.), Lahousse, L. (Lies), Latourelle, J.C. (Jeanne), Smith, A.V. (Albert), Bartz, T.M. (Traci M.), Feitosa, M.F. (Mary Furlan), Gao, W. (Wei), Ahluwalia, T.S. (Tarunveer Singh), Tang, W. (Wenbo), Oldmeadow, C. (Christopher), Duan, Q. (Qing), Jong, K. (Kim) de, Wojczynski, M.K. (Mary ), Wang, X.-Q. (Xin-Qun), Noordam, R. (Raymond), Hartwig, F.P. (Fernando Pires), Jackson, V.E. (Victoria E.), Wang, T. (Tianyuan), Obeidat, M. (Ma’en), Hobbs, B.D. (Brian D.), Huan, T. (Tianxiao), Gui, H. (Hongsheng), Parker, M.M. (Margaret M.), Hu, D. (Donglei), Mogil, L.S. (Lauren S.), Kichaev, G. (Gleb), Jin, J. (Jianping), Graff, M.J. (Maud J.L.), Harris, T.B. (Tamara), Kalhan, R. (Ravi), Heckbert, S.R. (Susan), Paternoster, L. (Lavinia), Burkart, K.M. (Kristin), Liu, Y. (YongMei), Holliday, E.G. (Elizabeth), Wilson, J.F. (James), Vonk, J.M. (Judith), Sanders, J.L. (Jason L.), Barr, R.G. (Graham), Mutsert, R. (Reneé) de, Menezes, A.M.B. (Ana Maria Baptista), Adams, H.H.H. (Hieab), Van Den Berge, M. (Maarten), Joehanes, R. (Roby), Levin, A.M. (Albert M.), Liberto, J. (Jennifer), Launer, L.J. (Lenore), Morrison, A.C. (Alanna), Sitlani, C.M. (Colleen), Celedón, J.C. (Juan C.), Kritchevsky, S.B. (Stephen), Scott, R.J. (Rodney J.), Christensen, K. (Kaare), Rotter, J.I. (Jerome I.), Bonten, T.N. (Tobias N.), Wehrmeister, F.C. (Fernando C.), Bossé, Y. (Yohan), Xiao, S. (Shujie), Oh, S. (Sam), Franceschini, N. (Nora), Brody, J.A. (Jennifer A.), Kaplan, R.C. (Robert), Lohman, K. (Kurt), McEvoy, M. (Mark), Province, M.A. (Mike), Rosendaal, F.R. (Frits), Taylor, K.D. (Kent), Nickle, D.C. (David C.), Williams, L.K. (L. Keoki), Burchard, E.G. (Esteban), Wheeler, H.E. (Heather), Sin, D.D. (Don D.), Gudnason, V. (Vilmundur), North, K.E. (Kari), Fornage, M. (Myriam), Psaty, B.M. (Bruce M.), Myers, R.H. (Richard), O’Connor, G. (George), Hansen, T. (Torben), Laurie, C.C. (Cathy C.), Cassano, P.A. (Patricia), Sung, J. (Joohon), Kim, W.J. (Woo Jin), Attia, J. (John), Lange, L.A. (Leslie), Boezen, H.M. (Marike), Thyagarajan, B. (Bharat), Rich, S.S. (Stephen), Mook-Kanamori, D.O. (Dennis O.), Horta, B.L. (Bernardo Lessa), Uitterlinden, A.G. (André), Im, H.K. (Hae Kyung), Cho, M.H. (Michael H.), Brusselle, G.G. (Guy), Gharib, S.A. (Sina), Dupuis, J. (Josée), Manichaikul, A. (Ani), and London, S.J. (Stephanie J.)

Abstract

Nearly 100 loci have been identified for pulmonary function, almost exclusively in studies of European ancestry populations. We extend previous research by meta-analyzing genome-wide association studies of 1000 Genomes imputed variants in relation to pulmonary function in a multiethnic population of 90,715 individuals of European (N = 60,552), African (N = 8429), Asian (N = 9959), and Hispanic/Latino (N = 11,775) ethnicities. We identify over 50 additional loci at genome-wide significance in ancestry-specific or multiethnic meta-analyses. Using recent fine-mapping methods incorporating functional annotation, gene expression, and differences in linkage disequilibrium between ethnicities, we further shed light on potential causal variants and genes at known and newly identified loci. Several of the novel genes encode proteins with predicted or established drug targets, including KCNK2 and CDK12. Our study highlights the utility of multiethnic and integrative genomics approaches to extend existing knowledge of the genetics of lu

Published
2018
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3. Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K i

Author

Feitosa, M.F. (Mary Furlan), Kraja, A. (Aldi), Chasman, D.I. (Daniel), Sung, Y.J. (Yun J.), Winkler, T.W. (Thomas W.), Ntalla, I. (Ioanna), Guo, X. (Xiuqing), Franceschini, N. (Nora), Cheng, C.-Y. (Ching-Yu), Sim, X. (Xueling), Vojinović, D. (Dina), Marten, J. (Jonathan), Musani, S.K. (Solomon K.), Li, C. (Changwei), Bentley, A.R. (Amy), Brown, M.R., Schwander, K., Richard, M.A. (Melissa A.), Noordam, R. (Raymond), Aschard, H. (Hugues), Bartz, T.M. (Traci M.), Bielak, L.F. (Lawrence F.), Dorajoo, R. (Rajkumar), Fisher, V. (Virginia), Hartwig, F.P. (Fernando P.), Horimoto, A.R.V.R. (Andrea R. V.R.), Lohman, K.K. (Kurt K.), Manning, A.K. (Alisa), Rankinen, T. (Tuomo), Smith, A.V. (Albert), Tajuddin, S.M. (Salman M.), Wojczynski, M.K. (Mary ), Alver, M. (Maris), Boissel, M. (Mathilde), Cai, Q. (Qiuyin), Campbell, A. (Archie), Chai, J.F. (Jin Fang), Chen, X. (Xu), Divers, J. (Jasmin), Gao, C. (Chuan), Goel, A. (Anuj), Hagemeijer, Y. (Yanick), Harris, S.E. (Sarah), He, M. (Meian), Hsu, F.-C. (Fang-Chi), Jackson, A.U. (Anne), Kähönen, M. (Mika), Kasturiratne, A. (Anuradhani), Komulainen, P. (Pirjo), Kuhnel, B. (Brigitte), Laguzzi, F. (Federica), Luan, J., Matoba, N. (Nana), Nolte, I.M. (Ilja), Padmanabhan, S. (Sandosh), Riaz, M. (Muhammad), Rueedi, R. (Rico), Robino, A. (Antonietta), Said, M.A. (M. Abdullah), Scott, R.A. (Robert), Sofer, T. (Tamar), Stancáková, A. (Alena), Takeuchi, F. (Fumihiko), Tayo, B. (Bamidele), Most, P.J. (Peter) van der, Varga, T.V. (Tibor V.), Vitart, V. (Veronique), Wang, Y. (Yajuan), Ware, E.B. (Erin B.), Warren, H. (Helen), Weiss, S. (Stefan), Wen, W. (Wanqing), Yanek, L.R. (Lisa), Zhang, W. (Weihua), Zhao, J.H. (Jing Hua), Afaq, S. (Saima), Amin, N. (Najaf), Amini, M. (Marzyeh), Arking, D.E. (Dan), Aung, T. (Tin), Boerwinkle, E. (Eric), Borecki, I.B. (Ingrid), Broeckel, U. (Ulrich), Brown, M. (Morris), Brumat, M. (Marco), Burke, G.L. (Greg), Canouil, M. (Mickaël), Chakravarti, A. (Aravinda), Charumathi, S. (Sabanayagam), Chen, Y.D.I. (Yii-Der Ida), Connell, J.M. (John M.), Correa, D.D., De Las Fuentes, L. (Lisa), Mutsert, R. (Reneé) de, De Silva, H.J. (H. Janaka), Deng, X. (Xuan), Ding, J. (Jingzhong), Duan, Q. (Qing), Eaton, C.B. (Charles B.), Ehret, G. (Georg), Eppinga, R.N. (Ruben N.), Evangelou, E. (Evangelos), Faul, J.D. (Jessica D.), Felix, S.B. (Stephan B.), Forouhi, N.G. (Nita), Forrester, T. (Terrence), Franco, O.H. (Oscar), Friedlander, Y. (Yechiel), Gandin, I. (Ilaria), Gao, H. (He), Ghanbari, M. (Mohsen), Gigante, B. (Bruna), Gu, C. (Charles), Gu, D. (Dongfeng), Hagenaars, S. (Saskia), Hallmans, G. (Göran), Harris, T.B. (Tamara), He, J. (Jiang), Heikkinen, S. (Sami), Heng, C.K. (Chew-Kiat), Hirata, M. (Makoto), Howard, B.V. (Barbara V.), Ikram, M.K. (Kamran), John, U. (Ulrich), Katsuya, T. (Tomohiro), Khor, C.C., Kilpeläinen, T.O. (Tuomas), Koh, W.-P. (Woon-Puay), Krieger, J.E. (José), Kritchevsky, S.B. (Stephen), Kubo, M. (Michiaki), Kuusisto, J. (Johanna), Lakka, T.A. (Timo), Langefeld, C.D. (Carl), Langenberg, C. (Claudia), Launer, L.J. (Lenore), Lehne, B. (Benjamin), Lewis, C.E. (Cora E.), Li, Y. (Yize), Lin, S. (Shiow), Liu, J. (Jianjun), Liu, J. (Jingmin), Loh, M. (Marie), Louie, T. (Tin), Mägi, R. (Reedik), McKenzie, C.A. (Colin), Meitinger, T. (Thomas), Metspalu, A. (Andres), Milaneschi, Y. (Yuri), Milani, L. (Lili), Mohlke, K.L. (Karen), Momozawa, Y. (Yukihide), Nalls, M.A. (Michael), Nelson, C.P. (Christopher P.), Sotoodehnia, N. (Nona), Norris, J.M. (Jill M.), O´Connell, J.R., Palmer, N.D. (Nicholette), Perls, T.T. (Thomas T.), Pedersen, N.L. (Nancy), Peters, A. (Annette), Peyser, P.A. (Patricia A.), Poulter, N.R. (Neil), Raffel, L.J. (Leslie J.), Raitakari, O. (Olli), Roll, K. (Kathryn), Rose, L.M. (Lynda M.), Rosendaal, F.R. (Frits), Rotter, J.I. (Jerome I.), Schmidt, C.O. (Carsten Oliver), Schreiner, P.J. (Pamela), Schupf, N. (Nicole), Scott, W.R. (William R.), Sever, P. (Peter), Shi, Y. (Yuan), Sidney, S. (Stephen), Sims, M. (Mario), Sitlani, C.M. (Colleen), Smith, J.A. (Jennifer A), Snieder, H. (Harold), Starr, J.M. (John), Strauch, K. (Konstantin), Stringham, H.M. (Heather M.), Tan, N.Y.Q. (Nicholas Y.Q.), Tang, H. (Hua), Taylor, K.D. (Kent), Teo, Y.Y. (Yik Ying), Tham, Y.C. (Yih Chung), Turner, S.T. (Stephen T.), Uitterlinden, A.G. (André), Vollenweider, P. (Peter), Waldenberger, M. (Melanie), Wang, L. (Lihua), Wang, Y.X. (Ya Xing), Wei, W.B. (Wen Bin), Williams, C. (Christine), Yao, J. (Jie), Yu, C. (Caizheng), Yuan, J.-M. (Jian-Min), Zhao, W. (Wei), Zonderman, A.B., Becker, D.M. (Diane), Boehnke, M. (Michael), Bowden, D.W. (Donald W.), Chambers, J.C. (John C.), Deary, I.J. (Ian), Esko, T. (Tõnu), Farrall, M. (Martin), Franks, P.W. (Paul W.), Freedman, B.I. (Barry), Froguel, P. (Philippe), Gasparini, P. (Paolo), Gieger, C. (Christian), Jonas, J.B. (Jost Bruno), Kamatani, Y. (Yoichiro), Kato, N. (Norihiro), Kooner, J.S. (Jaspal S.), Kutalik, Z. (Zoltán), Laakso, M. (Markku), Laurie, C.C. (Cathy C.), Leander, K. (Karin), Lehtimäki, T. (Terho), Magnusson, P.K. (Patrik), Oldehinkel, A.J. (Albertine), Penninx, B.W.J.H. (Brenda), Polasek, O. (Ozren), Porteous, D.J. (David J.), Rauramaa, R. (Rainer), Samani, N.J. (Nilesh J.), Scott, J. (James), Shu, X.-O. (Xiao-Ou), Van Der Harst, P. (Pim), Wagenknecht, L.E. (Lynne), Wareham, N.J. (Nick), Watkins, H. (Hugh), Weir, D.R. (David R.), Wickremasinghe, A.R. (Ananda), Wu, T. (Tangchun), Zheng, W. (Wei), Bouchard, C. (Claude), Christensen, K. (Kaare), Evans, M.K. (Michele), Gudnason, V. (Vilmundur), Horta, B.L. (Bernardo L.), Kardia, S.L.R. (Sharon L.R.), Liu, Y. (YongMei), Pereira, A.C. (Alexandre C.), Psaty, B.M. (Bruce M.), Ridker, P.M. (Paul), Dam, R.M. (Rob) van, Gauderman, W.J. (W James), Zhu, X. (Xiaofeng), Mook-Kanamori, D.O. (Dennis O.), Fornage, M. (Myriam), Rotimi, C. (Charles), Cupples, L.A. (Adrienne), Kelly, T.N. (Tanika N.), Fox, E.R. (Ervin), Hayward, C. (Caroline), Duijn, C.M. (Cornelia) van, Tai, E.S. (E. Shyong), Wong, T.Y. (Tien Yin), Kooperberg, C. (Charles), Palmas, W. (Walter), Rice, K.M. (Kenneth), Morrison, A.C. (Alanna), Elliott, P. (Paul), Caulfield, M. (Mark), Munroe, P. (Patricia), Rao, D.C. (Dabeeru C.), Province, M.A. (Mike), Levy, D. (Daniel), Feitosa, M.F. (Mary Furlan), Kraja, A. (Aldi), Chasman, D.I. (Daniel), Sung, Y.J. (Yun J.), Winkler, T.W. (Thomas W.), Ntalla, I. (Ioanna), Guo, X. (Xiuqing), Franceschini, N. (Nora), Cheng, C.-Y. (Ching-Yu), Sim, X. (Xueling), Vojinović, D. (Dina), Marten, J. (Jonathan), Musani, S.K. (Solomon K.), Li, C. (Changwei), Bentley, A.R. (Amy), Brown, M.R., Schwander, K., Richard, M.A. (Melissa A.), Noordam, R. (Raymond), Aschard, H. (Hugues), Bartz, T.M. (Traci M.), Bielak, L.F. (Lawrence F.), Dorajoo, R. (Rajkumar), Fisher, V. (Virginia), Hartwig, F.P. (Fernando P.), Horimoto, A.R.V.R. (Andrea R. V.R.), Lohman, K.K. (Kurt K.), Manning, A.K. (Alisa), Rankinen, T. (Tuomo), Smith, A.V. (Albert), Tajuddin, S.M. (Salman M.), Wojczynski, M.K. (Mary ), Alver, M. (Maris), Boissel, M. (Mathilde), Cai, Q. (Qiuyin), Campbell, A. (Archie), Chai, J.F. (Jin Fang), Chen, X. (Xu), Divers, J. (Jasmin), Gao, C. (Chuan), Goel, A. (Anuj), Hagemeijer, Y. (Yanick), Harris, S.E. (Sarah), He, M. (Meian), Hsu, F.-C. (Fang-Chi), Jackson, A.U. (Anne), Kähönen, M. (Mika), Kasturiratne, A. (Anuradhani), Komulainen, P. (Pirjo), Kuhnel, B. (Brigitte), Laguzzi, F. (Federica), Luan, J., Matoba, N. (Nana), Nolte, I.M. (Ilja), Padmanabhan, S. (Sandosh), Riaz, M. (Muhammad), Rueedi, R. (Rico), Robino, A. (Antonietta), Said, M.A. (M. Abdullah), Scott, R.A. (Robert), Sofer, T. (Tamar), Stancáková, A. (Alena), Takeuchi, F. (Fumihiko), Tayo, B. (Bamidele), Most, P.J. (Peter) van der, Varga, T.V. (Tibor V.), Vitart, V. (Veronique), Wang, Y. (Yajuan), Ware, E.B. (Erin B.), Warren, H. (Helen), Weiss, S. (Stefan), Wen, W. (Wanqing), Yanek, L.R. (Lisa), Zhang, W. (Weihua), Zhao, J.H. (Jing Hua), Afaq, S. (Saima), Amin, N. (Najaf), Amini, M. (Marzyeh), Arking, D.E. (Dan), Aung, T. (Tin), Boerwinkle, E. (Eric), Borecki, I.B. (Ingrid), Broeckel, U. (Ulrich), Brown, M. (Morris), Brumat, M. (Marco), Burke, G.L. (Greg), Canouil, M. (Mickaël), Chakravarti, A. (Aravinda), Charumathi, S. (Sabanayagam), Chen, Y.D.I. (Yii-Der Ida), Connell, J.M. (John M.), Correa, D.D., De Las Fuentes, L. (Lisa), Mutsert, R. (Reneé) de, De Silva, H.J. (H. Janaka), Deng, X. (Xuan), Ding, J. (Jingzhong), Duan, Q. (Qing), Eaton, C.B. (Charles B.), Ehret, G. (Georg), Eppinga, R.N. (Ruben N.), Evangelou, E. (Evangelos), Faul, J.D. (Jessica D.), Felix, S.B. (Stephan B.), Forouhi, N.G. (Nita), Forrester, T. (Terrence), Franco, O.H. (Oscar), Friedlander, Y. (Yechiel), Gandin, I. (Ilaria), Gao, H. (He), Ghanbari, M. (Mohsen), Gigante, B. (Bruna), Gu, C. (Charles), Gu, D. (Dongfeng), Hagenaars, S. (Saskia), Hallmans, G. (Göran), Harris, T.B. (Tamara), He, J. (Jiang), Heikkinen, S. (Sami), Heng, C.K. (Chew-Kiat), Hirata, M. (Makoto), Howard, B.V. (Barbara V.), Ikram, M.K. (Kamran), John, U. (Ulrich), Katsuya, T. (Tomohiro), Khor, C.C., Kilpeläinen, T.O. (Tuomas), Koh, W.-P. (Woon-Puay), Krieger, J.E. (José), Kritchevsky, S.B. (Stephen), Kubo, M. (Michiaki), Kuusisto, J. (Johanna), Lakka, T.A. (Timo), Langefeld, C.D. (Carl), Langenberg, C. (Claudia), Launer, L.J. (Lenore), Lehne, B. (Benjamin), Lewis, C.E. (Cora E.), Li, Y. (Yize), Lin, S. (Shiow), Liu, J. (Jianjun), Liu, J. (Jingmin), Loh, M. (Marie), Louie, T. (Tin), Mägi, R. (Reedik), McKenzie, C.A. (Colin), Meitinger, T. (Thomas), Metspalu, A. (Andres), Milaneschi, Y. (Yuri), Milani, L. (Lili), Mohlke, K.L. (Karen), Momozawa, Y. (Yukihide), Nalls, M.A. (Michael), Nelson, C.P. (Christopher P.), Sotoodehnia, N. (Nona), Norris, J.M. (Jill M.), O´Connell, J.R., Palmer, N.D. (Nicholette), Perls, T.T. (Thomas T.), Pedersen, N.L. (Nancy), Peters, A. (Annette), Peyser, P.A. (Patricia A.), Poulter, N.R. (Neil), Raffel, L.J. (Leslie J.), Raitakari, O. (Olli), Roll, K. (Kathryn), Rose, L.M. (Lynda M.), Rosendaal, F.R. (Frits), Rotter, J.I. (Jerome I.), Schmidt, C.O. (Carsten Oliver), Schreiner, P.J. (Pamela), Schupf, N. (Nicole), Scott, W.R. (William R.), Sever, P. (Peter), Shi, Y. (Yuan), Sidney, S. (Stephen), Sims, M. (Mario), Sitlani, C.M. (Colleen), Smith, J.A. (Jennifer A), Snieder, H. (Harold), Starr, J.M. (John), Strauch, K. (Konstantin), Stringham, H.M. (Heather M.), Tan, N.Y.Q. (Nicholas Y.Q.), Tang, H. (Hua), Taylor, K.D. (Kent), Teo, Y.Y. (Yik Ying), Tham, Y.C. (Yih Chung), Turner, S.T. (Stephen T.), Uitterlinden, A.G. (André), Vollenweider, P. (Peter), Waldenberger, M. (Melanie), Wang, L. (Lihua), Wang, Y.X. (Ya Xing), Wei, W.B. (Wen Bin), Williams, C. (Christine), Yao, J. (Jie), Yu, C. (Caizheng), Yuan, J.-M. (Jian-Min), Zhao, W. (Wei), Zonderman, A.B., Becker, D.M. (Diane), Boehnke, M. (Michael), Bowden, D.W. (Donald W.), Chambers, J.C. (John C.), Deary, I.J. (Ian), Esko, T. (Tõnu), Farrall, M. (Martin), Franks, P.W. (Paul W.), Freedman, B.I. (Barry), Froguel, P. (Philippe), Gasparini, P. (Paolo), Gieger, C. (Christian), Jonas, J.B. (Jost Bruno), Kamatani, Y. (Yoichiro), Kato, N. (Norihiro), Kooner, J.S. (Jaspal S.), Kutalik, Z. (Zoltán), Laakso, M. (Markku), Laurie, C.C. (Cathy C.), Leander, K. (Karin), Lehtimäki, T. (Terho), Magnusson, P.K. (Patrik), Oldehinkel, A.J. (Albertine), Penninx, B.W.J.H. (Brenda), Polasek, O. (Ozren), Porteous, D.J. (David J.), Rauramaa, R. (Rainer), Samani, N.J. (Nilesh J.), Scott, J. (James), Shu, X.-O. (Xiao-Ou), Van Der Harst, P. (Pim), Wagenknecht, L.E. (Lynne), Wareham, N.J. (Nick), Watkins, H. (Hugh), Weir, D.R. (David R.), Wickremasinghe, A.R. (Ananda), Wu, T. (Tangchun), Zheng, W. (Wei), Bouchard, C. (Claude), Christensen, K. (Kaare), Evans, M.K. (Michele), Gudnason, V. (Vilmundur), Horta, B.L. (Bernardo L.), Kardia, S.L.R. (Sharon L.R.), Liu, Y. (YongMei), Pereira, A.C. (Alexandre C.), Psaty, B.M. (Bruce M.), Ridker, P.M. (Paul), Dam, R.M. (Rob) van, Gauderman, W.J. (W James), Zhu, X. (Xiaofeng), Mook-Kanamori, D.O. (Dennis O.), Fornage, M. (Myriam), Rotimi, C. (Charles), Cupples, L.A. (Adrienne), Kelly, T.N. (Tanika N.), Fox, E.R. (Ervin), Hayward, C. (Caroline), Duijn, C.M. (Cornelia) van, Tai, E.S. (E. Shyong), Wong, T.Y. (Tien Yin), Kooperberg, C. (Charles), Palmas, W. (Walter), Rice, K.M. (Kenneth), Morrison, A.C. (Alanna), Elliott, P. (Paul), Caulfield, M. (Mark), Munroe, P. (Patricia), Rao, D.C. (Dabeeru C.), Province, M.A. (Mike), and Levy, D. (Daniel)

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 × 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 × 10-8). For African ancestry samples, we detected 18 potentially novel BP loci (P < 5.0 × 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.

Published
2018
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4. Low-Frequency Synonymous Coding Variation in CYP2R1 Has Large Effects on Vitamin D Levels and Risk of Multiple Sclerosis

Author

Manousaki, D. (Despoina), Dudding, T. (Tom), Haworth, S. (Simon), Hsu, Y.-H. (Yi-Hsiang), Liu, C.-T. (Ching-Ti), Medina-Gomez, M.C. (Carolina), Voortman, R.G. (Trudy), Velde, N. (Nathalie) van der, Melhus, H. (Håkan), Robinson-Cohen, C. (Cassianne), Cousminer, D.L. (Diana), Nethander, M. (Maria), Vandenput, L. (Liesbeth), Noordam, R., Forgetta, V. (Vincenzo), Greenwood, C.M.T. (Celia), Biggs, M.L. (M.), Psaty, B.M. (Bruce M.), Rotter, J.I. (Jerome I.), Zemel, B.S. (Babette S.), Mitchell, J.A. (Jonathan A.), Taylor, B. (Bruce), Lorentzon, M. (Mattias), Karlsson, M. (Magnus), Jaddoe, V.W.V. (Vincent), Tiemeier, H.W. (Henning), Campos Obando, N. (Natalia), Franco, O.H. (Oscar), Uitterlinden, A.G. (André), Broer, L. (Linda), Schoor, N.M. (Natasja) van, Ham, A.C. (Annelies), Ikram, M.K. (Kamran), Karasik, D. (David), Mutsert, R. (Reneé) de, Rosendaal, F.R. (Frits), Heijer, M. (Martin) den, Wang, T.J. (Thomas), Kao, W.H.L. (Wen), Orwoll, E.S. (Eric), Mook-Kanamori, D.O. (Dennis), Michaëlsson, K. (Karl), Kestenbaum, B. (Bryan), Ohlsson, C. (Claes), Mellström, D. (Dan), Groot, L.C.P.G.M. (Lisette) de, Grant, S.F.A. (Struan), Kiel, D.P. (Douglas P.), Zillikens, M.C. (Carola), Rivadeneira Ramirez, F. (Fernando), Sawcer, S.J. (Stephen), Timpson, N.J. (Nicholas), Richards, J.B. (Brent), Manousaki, D. (Despoina), Dudding, T. (Tom), Haworth, S. (Simon), Hsu, Y.-H. (Yi-Hsiang), Liu, C.-T. (Ching-Ti), Medina-Gomez, M.C. (Carolina), Voortman, R.G. (Trudy), Velde, N. (Nathalie) van der, Melhus, H. (Håkan), Robinson-Cohen, C. (Cassianne), Cousminer, D.L. (Diana), Nethander, M. (Maria), Vandenput, L. (Liesbeth), Noordam, R., Forgetta, V. (Vincenzo), Greenwood, C.M.T. (Celia), Biggs, M.L. (M.), Psaty, B.M. (Bruce M.), Rotter, J.I. (Jerome I.), Zemel, B.S. (Babette S.), Mitchell, J.A. (Jonathan A.), Taylor, B. (Bruce), Lorentzon, M. (Mattias), Karlsson, M. (Magnus), Jaddoe, V.W.V. (Vincent), Tiemeier, H.W. (Henning), Campos Obando, N. (Natalia), Franco, O.H. (Oscar), Uitterlinden, A.G. (André), Broer, L. (Linda), Schoor, N.M. (Natasja) van, Ham, A.C. (Annelies), Ikram, M.K. (Kamran), Karasik, D. (David), Mutsert, R. (Reneé) de, Rosendaal, F.R. (Frits), Heijer, M. (Martin) den, Wang, T.J. (Thomas), Kao, W.H.L. (Wen), Orwoll, E.S. (Eric), Mook-Kanamori, D.O. (Dennis), Michaëlsson, K. (Karl), Kestenbaum, B. (Bryan), Ohlsson, C. (Claes), Mellström, D. (Dan), Groot, L.C.P.G.M. (Lisette) de, Grant, S.F.A. (Struan), Kiel, D.P. (Douglas P.), Zillikens, M.C. (Carola), Rivadeneira Ramirez, F. (Fernando), Sawcer, S.J. (Stephen), Timpson, N.J. (Nicholas), and Richards, J.B. (Brent)

Abstract

Vitamin D insufficiency is common, correctable, and influenced by genetic factors, and it has been associated with risk of several diseases. We sought to identify low-frequency genetic variants that strongly increase the risk of vitamin D insufficiency and tested their effect on risk of multiple sclerosis, a disease influenced by low vitamin D concentrations. We used whole-genome sequencing data from 2,619 individuals through the UK10K program and deep-imputation data from 39,655 individuals genotyped genome-wide. Meta-analysis of the summary statistics from 19 cohorts identified in CYP2R1 the low-frequency synonymous coding variant g.14900931G>A, which conferred a large effect on 25-hydroxyvitamin D levels. The effect on 25OHD was four times larger and independent of the effect of a previously described common variant near CYP2R1. By analyzing 8,711 individuals, we showed that heterozygote carriers of this low-frequency variant have an increased risk of vitamin D insufficiency. Individuals carrying one copy of this variant also had increased odds of multiple sclerosis in a sample of 5,927 case and 5,599 control subjects. In conclusion, we describe a low-frequency CYP2R1 coding variant that exerts the largest effect upon 25OHD levels identified to date in the general European population and implicates vitamin

Published
2017
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5. Genome-wide associations for birth weight and correlations with adult disease

Author

Horikoshi, M. (Momoko), Beaumont, R.N. (Robin N.), Day, F.R. (Felix), Warrington, N.M. (Nicole), Kooijman, M.N. (Marjolein), Fernandez-Tajes, J. (Juan), Feenstra, B. (Bjarke), Van Zuydam, N.R. (Natalie R.), Gaulton, K. (Kyle), Grarup, N. (Niels), Bradfield, J.P. (Jonathan), Strachan, D.P. (David), Li-Gao, R. (Ruifang), Ahluwalia, T.S. (Tarunveer Singh), Kreiner, E. (Eskil), Rueedi, R. (Rico), Lyytikäinen, L.-P. (Leo-Pekka), Cousminer, D.L. (Diana), Wu, Y. (Ying), Thiering, E. (Elisabeth), Wang, C.A. (Carol A.), Have, C.T. (Christian T.), Hottenga, J.J. (Jouke Jan), Vilor-Tejedor, N. (Natàlia), Joshi, P.K. (Peter), Boh, E.T.H. (Eileen Tai Hui), Ntalla, I. (Ioanna), Pitkanen, N. (Niina), Mahajan, A. (Anubha), Leeuwen, E.M. (Elisa) van, Joro, R. (Raimo), Lagou, V. (Vasiliki), Nodzenski, M. (Michael), Diver, L.A. (Louise A.), Zondervan, K.T. (Krina), Bustamante, M. (Mariona), Marques-Vidal, P. (Pedro), Mercader, J.M. (Josep), Bennett, A.J. (Amanda), Rahmioglu, N. (Nilufer), Nyholt, D.R. (Dale), Ma, R.C.W. (Ronald C. W.), Tam, C.H.T. (Claudia H. T.), Tam, W.H. (Wing Hung), Ganesh, S.K. (Santhi), Rooij, F.J.A. (Frank) van, Jones, S.E. (Samuel E.), Loh, P.-R. (Po-Ru), Ruth, K.S. (Katherine S.), Tuke, M.A. (Marcus A.), Tyrrell, A.W.R., Wood, A.R. (Andrew), Yaghootkar, H. (Hanieh), Scholtens, D.M. (Denise M.), Paternoster, L. (Lavinia), Prokopenko, I. (Inga), Kovacs, P. (Peter), Atalay, M. (Mustafa), Willems, S.M. (Sara), Panoutsopoulou, K. (Kalliope), Wang, X. (Xu), Carstensen, L. (Lisbeth), Geller, F. (Frank), Schraut, K.E. (Katharina E.), Murcia, M. (Mario), Beijsterveldt, C.E.M. (Toos) van, Willemsen, G.A.H.M. (Gonneke), Appel, E.V.R. (Emil V. R.), Fonvig, C.E. (Cilius E.), Trier, C. (Caecilie), Tiesler, C.M.T. (Carla M. T.), Standl, E. (Eberhard), Kutalik, Z. (Zoltán), Bonàs-Guarch, S. (Silvia), Hougaard, D.M. (David), Sánchez, F. (Friman), Torrents, D. (David), Waage, J. (Johannes), Hollegaard, M.V. (Mads V), Haan, H.G. (Hugoline) de, Rosendaal, F.R. (Frits), Medina-Gomez, C. (Carolina), Ring, S.M. (Susan), Hemani, G., Mcmahon, G. (George), Robertson, N.R. (Neil), Groves, C.J. (Christopher), Langenberg, C. (Claudia), Luan, J. (Jian'An), Scott, R.A. (Robert), Zhao, J.H. (Jing Hua), Mentch, F.D. (Frank), MacKenzie, S.M. (Scott M.), Reynolds, R.M. (Rebecca), Lowe Jr., W.L. (William), Tönjes, A. (Anke), Stumvoll, M. (Michael), Lindi, V. (Virpi), Lakka, T.A. (Timo), Duijn, C.M. (Cornelia) van, Kieß, W. (Wieland), KöRner, A. (Antje), Sørensen, T.I.A. (Thorkild), Niinikoski, H. (Harri), Pahkala, K. (Katja), Raitakari, O.T. (Olli T.), Zeggini, E. (Eleftheria), Dedoussis, G.V. (George), Teo, Y.Y. (Yik Ying), Saw, S.-M. (Seang-Mei), Melbye, M. (Mads), Campbell, H. (Harry), Wilson, J.F. (James F.), Vrijheid, M. (Martine), Geus, E.J.C. (Eco) de, Boomsma, D.I. (Dorret), Kadarmideen, H.N. (Haja N.), Holm, J.-C. (Jens-Christian), Hansen, T. (T.), Sebert, S. (Sylvain), Hattersley, A.T. (Andrew), Beilin, L.J. (Lawrence), Newnham, J.P. (John), Pennell, C.E. (Craig), Heinrich, J. (Joachim), Adair, L.S. (Linda), Borja, J.B. (Judith), Mohlke, K.L. (Karen), Hagen, K. (Knut), Widen, E. (Elisabeth), Kähönen, M. (Mika), Viikari, J. (Jorma), Lehtimäki, T. (Terho), Vollenweider, P. (Peter), Bønnelykke, K. (Klaus), Bisgaard, H. (Hans), Mook-Kanamori, D.O. (Dennis), Hofman, A. (Albert), Rivadeneira Ramirez, F. (Fernando), Uitterlinden, A.G. (André), Pisinger, C. (Charlotta), Pedersen, O. (Oluf), Power, C. (Christopher), Hypponen, E. (Elina), Wareham, N.J. (Nick), Hakonarson, H. (Hakon), Davies, E. (Eleanor), Walker, B.R. (Brian R.), Jaddoe, V.W.V. (Vincent), Jarvelin, M.-R. (Marjo-Riitta), Grant, S.F.A. (Struan), Vaag, A.A. (Allan A.), Lawlor, D.A. (Debbie), Frayling, T.M. (Timothy), Smith, A.V. (Davey), Morris, A.P. (Andrew), Ong, K.K. (Ken), Felix, J.F. (Janine), Timpson, N.J. (Nicholas), Perry, J.R.B. (John), Evans, D.M. (David), McCarthy, M.I. (Mark), Freathy, R.M. (Rachel), Horikoshi, M. (Momoko), Beaumont, R.N. (Robin N.), Day, F.R. (Felix), Warrington, N.M. (Nicole), Kooijman, M.N. (Marjolein), Fernandez-Tajes, J. (Juan), Feenstra, B. (Bjarke), Van Zuydam, N.R. (Natalie R.), Gaulton, K. (Kyle), Grarup, N. (Niels), Bradfield, J.P. (Jonathan), Strachan, D.P. (David), Li-Gao, R. (Ruifang), Ahluwalia, T.S. (Tarunveer Singh), Kreiner, E. (Eskil), Rueedi, R. (Rico), Lyytikäinen, L.-P. (Leo-Pekka), Cousminer, D.L. (Diana), Wu, Y. (Ying), Thiering, E. (Elisabeth), Wang, C.A. (Carol A.), Have, C.T. (Christian T.), Hottenga, J.J. (Jouke Jan), Vilor-Tejedor, N. (Natàlia), Joshi, P.K. (Peter), Boh, E.T.H. (Eileen Tai Hui), Ntalla, I. (Ioanna), Pitkanen, N. (Niina), Mahajan, A. (Anubha), Leeuwen, E.M. (Elisa) van, Joro, R. (Raimo), Lagou, V. (Vasiliki), Nodzenski, M. (Michael), Diver, L.A. (Louise A.), Zondervan, K.T. (Krina), Bustamante, M. (Mariona), Marques-Vidal, P. (Pedro), Mercader, J.M. (Josep), Bennett, A.J. (Amanda), Rahmioglu, N. (Nilufer), Nyholt, D.R. (Dale), Ma, R.C.W. (Ronald C. W.), Tam, C.H.T. (Claudia H. T.), Tam, W.H. (Wing Hung), Ganesh, S.K. (Santhi), Rooij, F.J.A. (Frank) van, Jones, S.E. (Samuel E.), Loh, P.-R. (Po-Ru), Ruth, K.S. (Katherine S.), Tuke, M.A. (Marcus A.), Tyrrell, A.W.R., Wood, A.R. (Andrew), Yaghootkar, H. (Hanieh), Scholtens, D.M. (Denise M.), Paternoster, L. (Lavinia), Prokopenko, I. (Inga), Kovacs, P. (Peter), Atalay, M. (Mustafa), Willems, S.M. (Sara), Panoutsopoulou, K. (Kalliope), Wang, X. (Xu), Carstensen, L. (Lisbeth), Geller, F. (Frank), Schraut, K.E. (Katharina E.), Murcia, M. (Mario), Beijsterveldt, C.E.M. (Toos) van, Willemsen, G.A.H.M. (Gonneke), Appel, E.V.R. (Emil V. R.), Fonvig, C.E. (Cilius E.), Trier, C. (Caecilie), Tiesler, C.M.T. (Carla M. T.), Standl, E. (Eberhard), Kutalik, Z. (Zoltán), Bonàs-Guarch, S. (Silvia), Hougaard, D.M. (David), Sánchez, F. (Friman), Torrents, D. (David), Waage, J. (Johannes), Hollegaard, M.V. (Mads V), Haan, H.G. (Hugoline) de, Rosendaal, F.R. (Frits), Medina-Gomez, C. (Carolina), Ring, S.M. (Susan), Hemani, G., Mcmahon, G. (George), Robertson, N.R. (Neil), Groves, C.J. (Christopher), Langenberg, C. (Claudia), Luan, J. (Jian'An), Scott, R.A. (Robert), Zhao, J.H. (Jing Hua), Mentch, F.D. (Frank), MacKenzie, S.M. (Scott M.), Reynolds, R.M. (Rebecca), Lowe Jr., W.L. (William), Tönjes, A. (Anke), Stumvoll, M. (Michael), Lindi, V. (Virpi), Lakka, T.A. (Timo), Duijn, C.M. (Cornelia) van, Kieß, W. (Wieland), KöRner, A. (Antje), Sørensen, T.I.A. (Thorkild), Niinikoski, H. (Harri), Pahkala, K. (Katja), Raitakari, O.T. (Olli T.), Zeggini, E. (Eleftheria), Dedoussis, G.V. (George), Teo, Y.Y. (Yik Ying), Saw, S.-M. (Seang-Mei), Melbye, M. (Mads), Campbell, H. (Harry), Wilson, J.F. (James F.), Vrijheid, M. (Martine), Geus, E.J.C. (Eco) de, Boomsma, D.I. (Dorret), Kadarmideen, H.N. (Haja N.), Holm, J.-C. (Jens-Christian), Hansen, T. (T.), Sebert, S. (Sylvain), Hattersley, A.T. (Andrew), Beilin, L.J. (Lawrence), Newnham, J.P. (John), Pennell, C.E. (Craig), Heinrich, J. (Joachim), Adair, L.S. (Linda), Borja, J.B. (Judith), Mohlke, K.L. (Karen), Hagen, K. (Knut), Widen, E. (Elisabeth), Kähönen, M. (Mika), Viikari, J. (Jorma), Lehtimäki, T. (Terho), Vollenweider, P. (Peter), Bønnelykke, K. (Klaus), Bisgaard, H. (Hans), Mook-Kanamori, D.O. (Dennis), Hofman, A. (Albert), Rivadeneira Ramirez, F. (Fernando), Uitterlinden, A.G. (André), Pisinger, C. (Charlotta), Pedersen, O. (Oluf), Power, C. (Christopher), Hypponen, E. (Elina), Wareham, N.J. (Nick), Hakonarson, H. (Hakon), Davies, E. (Eleanor), Walker, B.R. (Brian R.), Jaddoe, V.W.V. (Vincent), Jarvelin, M.-R. (Marjo-Riitta), Grant, S.F.A. (Struan), Vaag, A.A. (Allan A.), Lawlor, D.A. (Debbie), Frayling, T.M. (Timothy), Smith, A.V. (Davey), Morris, A.P. (Andrew), Ong, K.K. (Ken), Felix, J.F. (Janine), Timpson, N.J. (Nicholas), Perry, J.R.B. (John), Evans, D.M. (David), McCarthy, M.I. (Mark), and Freathy, R.M. (Rachel)

Abstract

Birth weight (BW) has been shown to be influenced by both fetal and maternal factors and in observational studies is reproducibly associated with future risk of adult metabolic diseases including type 2 diabetes (T2D) and cardiovascular disease1. These lifecourse associations have often been attributed to the impact of an adverse early life environment. Here, we performed a multi-ancestry genome-wide association study (GWAS) meta-analysis of BW in 153,781 individuals, identifying 60 loci where fetal genotype was associated with BW (P < 5 × 10-8). Overall, approximately 15% of variance in BW was captured by assays of fetal genetic variation. Using genetic association alone, we found strong inverse genetic correlations between BW and systolic blood pressure (Rg =-0.22, P = 5.5 × 10-13), T2D (Rg =-0.27, P = 1.1 × 10-6) and coronary artery disease (Rg =-0.30, P = 6.5 × 10-9). In addition, using large-cohort datasets, we demonstrated that genetic factors were the major contributor to the negative covariance between BW and future cardiometabolic risk. Pathway analyses indicated that the protein products of genes within BW-associated regions were enriched for diverse processes including insulin signalling, glucose homeostasis, glycogen biosynthesis and chromatin remodelling. There was also enrichment of associations with BW in known imprinted regions (P = 1.9 × 10-4). We demonstrate that life-course associations between early growth phenotypes and adult cardiometabolic disease are in part the result of shared genetic effects and identify some of the pathways through which these causal genetic effects are mediated.

Published
2016
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6. A randomized trial of genotype-guided dosing of acenocoumarol and phenprocoumon

Author

Verhoef, T.I. (Talitha), Ragia, G. (Georgia), Boer, A.C. (Anton) de, Barallon, R. (Rita), Kolovou, G. (Genovefa), Konstantinides, S. (Stavros), Cessie, S. (Saskia) le, Maltezos, E. (Efstratios), Meer, F.J.M. (Felix) van der, Redekop, W.K. (Ken), Remkes, P.A.J., Rosendaal, F.R. (Frits), Schie, R.F.M. (Rianne) van, Tavridou, A. (Anna), Tziakas, D. (Dimitrios), Wadelius, M. (Mia), Manolopoulos, V.G. (Vangelis), Maitland-van der Zee, A-H. (Anke-Hilse), Verhoef, T.I. (Talitha), Ragia, G. (Georgia), Boer, A.C. (Anton) de, Barallon, R. (Rita), Kolovou, G. (Genovefa), Konstantinides, S. (Stavros), Cessie, S. (Saskia) le, Maltezos, E. (Efstratios), Meer, F.J.M. (Felix) van der, Redekop, W.K. (Ken), Remkes, P.A.J., Rosendaal, F.R. (Frits), Schie, R.F.M. (Rianne) van, Tavridou, A. (Anna), Tziakas, D. (Dimitrios), Wadelius, M. (Mia), Manolopoulos, V.G. (Vangelis), and Maitland-van der Zee, A-H. (Anke-Hilse)

Abstract

BACKGROUND: Observational evidence suggests that the use of a genotype-guided dosing algorithm may increase the effectiveness and safety of acenocoumarol and phenprocoumon therapy. METHODS: We conducted two single-blind, randomized trials comparing a genotype-guided dosing algorithm that included clinical variables and genotyping for CYP2C9 and VKORC1 with a dosing algorithm that included only clinical variables, for the initiation of acenocoumarol or phenprocoumon treatment in patients with atrial fibrillation or venous thromboembolism. The primary outcome was the percentage of time in the target range for the international normalized ratio (INR; target range, 2.0 to 3.0) in the 12-week period after the initiation of therapy. Owing to low enrollment, the two trials were combined for analysis. The primary outcome was assessed in patients who remained in the trial for at least 10 weeks. RESULTS: A total of 548 patients were enrolled (273 patients in the genotype-guided group and 275 in the control group). The follow-up was at least 10 weeks for 239 patients in the genotype-guided group and 245 in the control group. The percentage of time in the therapeutic INR range was 61.6% for patients receiving genotype-guided dosing and 60.2% for those receiving clinically guided dosing (P = 0.52). There were no significant differences between the two groups for several secondary outcomes. The percentage of time in the therapeutic range during the first 4 weeks after the initiation of treatment in the two groups was 52.8% and 47.5% (P = 0.02), respectively. There were no significant differences with respect to the incidence of bleeding or thromboembolic events. CONCLUSIONS: Genotype-guided dosing of acenocoumarol or phenprocoumon did not improve the percentage of time in the therapeutic INR range during the 12 weeks after the initiation of therapy. Copyright

Published
2013
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7. Parenteral Pethidine for labour pain relief and substance use disorder: 20-Year follow-up cohort study in offspring

Author

Pereira, R. (Rob Rodrigues), Kanhai, H.H.H. (Humphrey), Rosendaal, F.R. (Frits R.), Dommelen, P. (Paula) van, Swaab, D.F. (Dick), Pereira, E.R. (Erik Rodrigues), Wetering, B.J.M. (Ben) van de, Pereira, R. (Rob Rodrigues), Kanhai, H.H.H. (Humphrey), Rosendaal, F.R. (Frits R.), Dommelen, P. (Paula) van, Swaab, D.F. (Dick), Pereira, E.R. (Erik Rodrigues), and Wetering, B.J.M. (Ben) van de

Abstract

Objective: To determine whether use of intrapartum Pethidine pain analgesia increases the risk for substance use disorder in adult offspring. Design: Analysis of data from a cohort study. Setting: Academic hospital in Leiden, the Netherlands. Participants: 133 cases and 164 control individuals, aged 18-20 years at follow-up. Main outcome measure: Incidence of substance use disorder or use of alcohol and tobacco. Results: The lifetime use of addictive substances in children exposed to intrapartum Pethidine analgesia was 45% of 133 children versus 48% of 164 not-exposed subjects (adjusted OR=0.79, 95% CI 0.48 to 1.29). Recent use of alcohol, tobacco and hard drugs showed no statistical difference either. Conclusion: Pethidine for labour pain medication appears not to be associated with substance misuse or smoking in later life.

Published
2012
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8. Prenatal diagnosis for haemophilia: A nationwide survey among female carriers in the Netherlands

Author

Balak, D.M.W. (Deepak), Gouw, S.C. (S.), Plug, I. (Iris), Mauser-Bunschoten, E.P. (Eveline), Vriends, A.H.J.T. (Anette), Diemen-Homan, J.E.M. (J. E M) van, Rosendaal, F.R. (Frits), Bom, J.G. (Anske) van der, Balak, D.M.W. (Deepak), Gouw, S.C. (S.), Plug, I. (Iris), Mauser-Bunschoten, E.P. (Eveline), Vriends, A.H.J.T. (Anette), Diemen-Homan, J.E.M. (J. E M) van, Rosendaal, F.R. (Frits), and Bom, J.G. (Anske) van der

Abstract

Carriers of haemophilia face difficult choices regarding prenatal diagnosis, but little is known about the determinants that influence their decisions. The aim of this study was to assess the incidence of prenatal diagnosis and potential determinants affecting the choice for prenatal diagnosis. A nationwide survey was performed among all women who underwent carriership testing for haemophilia in the Netherlands between 1992 and 2004. Prenatal diagnosis was assessed in

Published
2012
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9. Genetic variation associated with plasma vonWillebrand factor levels and the risk of incident venous thrombosis

Author

Smith, N.L. (Nicholas), Rice, K.M. (Kenneth), Bovill, E.G. (Edwin G.), Cushman, M. (Mary Ann), Bis, J.C. (Joshua), McKnight, B. (Barbara), Lumley, T. (Thomas), Glazer, N.L. (Nicole), Hylckama Vlieg, A. (Astrid) van, Tang, W. (Weihong), Dehghan, A. (Abbas), Strachan, D.P. (David), O'Donnell, C.J. (Christopher), Rotter, J.I. (Jerome), Heckbert, S.R. (Susan), Psaty, B.M. (Bruce), Rosendaal, F.R. (Frits), Smith, N.L. (Nicholas), Rice, K.M. (Kenneth), Bovill, E.G. (Edwin G.), Cushman, M. (Mary Ann), Bis, J.C. (Joshua), McKnight, B. (Barbara), Lumley, T. (Thomas), Glazer, N.L. (Nicole), Hylckama Vlieg, A. (Astrid) van, Tang, W. (Weihong), Dehghan, A. (Abbas), Strachan, D.P. (David), O'Donnell, C.J. (Christopher), Rotter, J.I. (Jerome), Heckbert, S.R. (Susan), Psaty, B.M. (Bruce), and Rosendaal, F.R. (Frits)

Abstract

In a recent genome-wide association study, variants in 8 genes were associated with VWF level, a risk factor for venous thrombosis (VT). In an independent, population-based, case-control study of incident VT, we tested hypotheses that variants in these genes would be associated with risk. Cases were 656 women who experienced an incident VT, and controls comprised 710 women without a history of VT. DNAwas obtained from whole blood. Logistic regression was used to test associations between incident VT and single nucleotide polymorphisms (SNPs) in 7 genes not previously shown to be associated with VT. Associations with P < .05 were candidates for replication in an independent case-control study of VT in both sexes. Two of the 7 SNPs tested yielded P < .05: rs1039084 (P = .005) in STXBP5, a novel candidate gene for VT, and rs1063856 (P = .04) in VWF, a gene whose protein level is associated with VT risk. Association results for the remaining 5 variants in SCARA5, STAB2, STX2, TC2N, and CLEC4M were not significant. Both STXBP5 and VWF findings were replicated successfully. Variation in genes associated with VWF levels in the genomewide association study was found to be independently associated with incident VT.

Published
2011
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10. Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease

Author

Schunkert, H. (Heribert), König, I.R. (Inke), Kathiresan, S. (Sekar), Reilly, M.P. (Muredach), Assimes, T.L. (Themistocles), Holm, H. (Hilma), Preuss, M. (Michael), Stewart, A.F.R. (Alexandre), Barbalic, M. (maja), Gieger, C. (Christian), Absher, D. (Devin), Aherrahrou, Z. (Zouhair), Allayee, H. (Hooman), Altshuler, D. (David), Anand, S.S. (Sonia), Andersen, K.K. (Karl), Anderson, J.L. (Jeffrey), Ardissino, D. (Diego), Ball, S.G. (Stephen), Balmforth, A.J. (Anthony), Barnes, T.A. (Timothy), Becker, D.M. (Diane), Berger, K. (Klaus), Bis, J.C. (Joshua), Boekholdt, S.M. (Matthijs), Boerwinkle, E.A. (Eric), Braund, P.S. (Peter), Brown, M.J. (Morris), Burnett, M.S., Buysschaert, I. (Ian), Carlquist, J.F. (John), Chen, L. (Li), Cichon, S. (Sven), Codd, V. (Veryan), Davies, R.W. (Robert), Dedoussis, G.V. (George), Dehghan, A. (Abbas), Demissie, S. (Serkalem), Devaney, J. (Joseph), Diemert, P. (Patrick), Do, R. (Ron), Doering, A. (Angela), Eifert, S. (Sandra), Mokhtari, N.E.E., Ellis, S.G. (Stephen), Elosua, R. (Roberto), Engert, J.C. (James), Epstein, S.E. (Stephen), Faire, U. (Ulf) de, Fischer, M. (Marcus), Folsom, A.R. (Aaron), Freyer, J. (Jennifer), Gigante, B. (Bruna), Girelli, D. (Domenico), Gretarsdottir, S. (Solveig), Gudnason, V. (Vilmundur), Gulcher, J.R. (Jeffrey), Halperin, E. (Eran), Hammond, N. (Naomi), Hazen, S.L. (Stanley), Hofman, A. (Albert), Horne, B.D. (Benjamin), Illig, T. (Thomas), Iribarren, C. (Carlos), Jones, G.T. (Gregory), Jukema, J.W. (Jan Wouter), Kaiser, M.A. (Michael), Kaplan, R.C. (Robert), Khaw, K-T. (Kay-Tee), Knowles, J.W. (Joshua), Kolovou, G. (Genovefa), Kong, A. (Augustine), Laaksonen, R. (Reijo), Lambrechts, D. (Diether), Leander, K. (Karin), Lettre, G. (Guillaume), Lieb, W. (Wolfgang), Loley, C. (Christina), Lotery, A.J. (Andrew), Mannucci, P.M. (Pier), Maouche, S. (Seraya), Martinelli, N. (Nicola), McKeown, P.P. (Pascal), Meisinger, C. (Christa), Meitinger, T. (Thomas), Melander, O. (Olle), Merlini, P.A., Mooser, V. (Vincent), Morgan, T. (Thomas), Mühleisen, T.W. (Thomas), Muhlestein, J.B. (Joseph), Münzel, T. (Thomas), Musunuru, K. (Kiran), Nahrstaedt, J. (Janja), Nelson, C.P. (Christopher P.), Nöthen, M.M. (Markus), Olivieri, O. (Oliviero), Patel, R.S. (Riyaz), Patterson, C.C. (Chris), Peters, A. (Annette), Peyvandi, F. (Flora), Qu, L. (Liming), Quyyumi, A.A. (Arshed), Rader, D.J. (Daniel), Rallidis, L.S. (Loukianos), Rice, C. (Catherine), Rosendaal, F.R. (Frits), Rubin, D. (Diana), Salomaa, V. (Veikko), Sampietro, M.L. (Maria Lourdes), Sandhu, M.S. (Manj), Schadt, E.E. (Eric), Schillert, A. (Arne), Schreiber, S. (Stefan), Schrezenmeir, J. (Jürgen), Schwartz, S.M. (Stephen), Siscovick, D.S. (David), Sivananthan, M. (Mohan), Sivapalaratnam, S. (Suthesh), Smith, A.V. (Albert Vernon), Snoep, J.D. (Jaapjan), Soranzo, N. (Nicole), Spertus, J.A. (John), Stark, K. (Klaus), Stirrups, K. (Kathy), Stoll, M. (Monika), Tang, W.H.W. (Wilson), Tennstedt, S. (Stephanie), Thorgeirsson, G. (Gudmundur), Thorleifsson, G. (Gudmar), Tomaszewski, M. (Maciej), Uitterlinden, A.G. (André), Rij, A.M. (Andre) van, Voight, B.F. (Benjamin), Wareham, N.J. (Nick), Wells, G.A. (George), Wichmann, H.E. (Heinz Erich), Wild, P.S. (Philipp), Willenborg, C. (Christina), Witteman, J.C.M. (Jacqueline), Wright, B.J. (Benjamin), Ye, S. (Shu), Zeller, T. (Tanja), Ziegler, A. (Andreas), Cambien, F. (François), Goodall, A.H. (Alison), Cupples, L.A. (Adrienne), Quertermous, T. (Thomas), Mäsignrz, W. (Winfried), Hengstenberg, C. (Christian), Blankenberg, S. (Stefan), Ouwehand, W.H. (Willem), Hall, A.S. (Alistair), Kastelein, J.J.P. (John), Deloukas, P. (Panagiotis), Thompson, J.R. (John), Stefansson, K. (Kari), Roberts, R. (Robert), Li, M. (Mingyao), Thorsteinsdottir, U. (Unnur), O'Donnell, C.J. (Christopher), McPherson, R. (Ruth), Erdmann, J. (Jeanette), Samani, N.J. (Nilesh), Schäffer, A. (Arne), Schunkert, H. (Heribert), König, I.R. (Inke), Kathiresan, S. (Sekar), Reilly, M.P. (Muredach), Assimes, T.L. (Themistocles), Holm, H. (Hilma), Preuss, M. (Michael), Stewart, A.F.R. (Alexandre), Barbalic, M. (maja), Gieger, C. (Christian), Absher, D. (Devin), Aherrahrou, Z. (Zouhair), Allayee, H. (Hooman), Altshuler, D. (David), Anand, S.S. (Sonia), Andersen, K.K. (Karl), Anderson, J.L. (Jeffrey), Ardissino, D. (Diego), Ball, S.G. (Stephen), Balmforth, A.J. (Anthony), Barnes, T.A. (Timothy), Becker, D.M. (Diane), Berger, K. (Klaus), Bis, J.C. (Joshua), Boekholdt, S.M. (Matthijs), Boerwinkle, E.A. (Eric), Braund, P.S. (Peter), Brown, M.J. (Morris), Burnett, M.S., Buysschaert, I. (Ian), Carlquist, J.F. (John), Chen, L. (Li), Cichon, S. (Sven), Codd, V. (Veryan), Davies, R.W. (Robert), Dedoussis, G.V. (George), Dehghan, A. (Abbas), Demissie, S. (Serkalem), Devaney, J. (Joseph), Diemert, P. (Patrick), Do, R. (Ron), Doering, A. (Angela), Eifert, S. (Sandra), Mokhtari, N.E.E., Ellis, S.G. (Stephen), Elosua, R. (Roberto), Engert, J.C. (James), Epstein, S.E. (Stephen), Faire, U. (Ulf) de, Fischer, M. (Marcus), Folsom, A.R. (Aaron), Freyer, J. (Jennifer), Gigante, B. (Bruna), Girelli, D. (Domenico), Gretarsdottir, S. (Solveig), Gudnason, V. (Vilmundur), Gulcher, J.R. (Jeffrey), Halperin, E. (Eran), Hammond, N. (Naomi), Hazen, S.L. (Stanley), Hofman, A. (Albert), Horne, B.D. (Benjamin), Illig, T. (Thomas), Iribarren, C. (Carlos), Jones, G.T. (Gregory), Jukema, J.W. (Jan Wouter), Kaiser, M.A. (Michael), Kaplan, R.C. (Robert), Khaw, K-T. (Kay-Tee), Knowles, J.W. (Joshua), Kolovou, G. (Genovefa), Kong, A. (Augustine), Laaksonen, R. (Reijo), Lambrechts, D. (Diether), Leander, K. (Karin), Lettre, G. (Guillaume), Lieb, W. (Wolfgang), Loley, C. (Christina), Lotery, A.J. (Andrew), Mannucci, P.M. (Pier), Maouche, S. (Seraya), Martinelli, N. (Nicola), McKeown, P.P. (Pascal), Meisinger, C. (Christa), Meitinger, T. (Thomas), Melander, O. (Olle), Merlini, P.A., Mooser, V. (Vincent), Morgan, T. (Thomas), Mühleisen, T.W. (Thomas), Muhlestein, J.B. (Joseph), Münzel, T. (Thomas), Musunuru, K. (Kiran), Nahrstaedt, J. (Janja), Nelson, C.P. (Christopher P.), Nöthen, M.M. (Markus), Olivieri, O. (Oliviero), Patel, R.S. (Riyaz), Patterson, C.C. (Chris), Peters, A. (Annette), Peyvandi, F. (Flora), Qu, L. (Liming), Quyyumi, A.A. (Arshed), Rader, D.J. (Daniel), Rallidis, L.S. (Loukianos), Rice, C. (Catherine), Rosendaal, F.R. (Frits), Rubin, D. (Diana), Salomaa, V. (Veikko), Sampietro, M.L. (Maria Lourdes), Sandhu, M.S. (Manj), Schadt, E.E. (Eric), Schillert, A. (Arne), Schreiber, S. (Stefan), Schrezenmeir, J. (Jürgen), Schwartz, S.M. (Stephen), Siscovick, D.S. (David), Sivananthan, M. (Mohan), Sivapalaratnam, S. (Suthesh), Smith, A.V. (Albert Vernon), Snoep, J.D. (Jaapjan), Soranzo, N. (Nicole), Spertus, J.A. (John), Stark, K. (Klaus), Stirrups, K. (Kathy), Stoll, M. (Monika), Tang, W.H.W. (Wilson), Tennstedt, S. (Stephanie), Thorgeirsson, G. (Gudmundur), Thorleifsson, G. (Gudmar), Tomaszewski, M. (Maciej), Uitterlinden, A.G. (André), Rij, A.M. (Andre) van, Voight, B.F. (Benjamin), Wareham, N.J. (Nick), Wells, G.A. (George), Wichmann, H.E. (Heinz Erich), Wild, P.S. (Philipp), Willenborg, C. (Christina), Witteman, J.C.M. (Jacqueline), Wright, B.J. (Benjamin), Ye, S. (Shu), Zeller, T. (Tanja), Ziegler, A. (Andreas), Cambien, F. (François), Goodall, A.H. (Alison), Cupples, L.A. (Adrienne), Quertermous, T. (Thomas), Mäsignrz, W. (Winfried), Hengstenberg, C. (Christian), Blankenberg, S. (Stefan), Ouwehand, W.H. (Willem), Hall, A.S. (Alistair), Kastelein, J.J.P. (John), Deloukas, P. (Panagiotis), Thompson, J.R. (John), Stefansson, K. (Kari), Roberts, R. (Robert), Li, M. (Mingyao), Thorsteinsdottir, U. (Unnur), O'Donnell, C.J. (Christopher), McPherson, R. (Ruth), Erdmann, J. (Jeanette), Samani, N.J. (Nilesh), and Schäffer, A. (Arne)

Abstract

We performed a meta-analysis of 14 genome-wide association studies of coronary artery disease (CAD) comprising 22,233 individuals with CAD (cases) and 64,762 controls of European descent followed by genotyping of top association signals in 56,682 additional individuals. This analysis identified 13 loci newly associated with CAD at P < 5 - 10'8 and confirmed the association of 10 of 12 previously reported CAD loci. The 13 new loci showed risk allele frequencies ranging from 0.13 to 0.91 and were associated with a 6% to 17% increase in the risk of CAD per allele. Notably, only three of the new loci showed significant association with traditional CAD risk factors and the majority lie in gene regions not previously implicated in the pathogenesis of CAD. Finally, five of the new CAD risk loci appear to have pleiotropic effects, showing strong association with various other human diseases or traits.

Published
2011
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11. Etiology, management, and outcome of the Budd-Chiari syndrome

Author

Darwish Murad, S. (Sarwa), Plessier, A. (Aurelie), Hernandez-Guerra, M. (Manuel), Fabris, F. (Federica Margherita), Eapen, C.E. (Chundamannil Eapen), Bahr, M.J. (Matthias), Trebicka, J. (Jonel), Morard, I. (Isabelle), Lasser, L. (Luc), Heller, J. (Jörg), Hadengue, A. (Antoine), Langlet, P. (Philippe), Miranda, H. (Helena), Primignani, M. (Massimo), Elias, E. (Elwyn), Leebeek, F.W.G. (Frank), Rosendaal, F.R. (Frits), Garcia-Pagan, J.C. (Juan Carlos), Valla, D.C. (Dominique Charle), Janssen, H.L.A. (Harry), Darwish Murad, S. (Sarwa), Plessier, A. (Aurelie), Hernandez-Guerra, M. (Manuel), Fabris, F. (Federica Margherita), Eapen, C.E. (Chundamannil Eapen), Bahr, M.J. (Matthias), Trebicka, J. (Jonel), Morard, I. (Isabelle), Lasser, L. (Luc), Heller, J. (Jörg), Hadengue, A. (Antoine), Langlet, P. (Philippe), Miranda, H. (Helena), Primignani, M. (Massimo), Elias, E. (Elwyn), Leebeek, F.W.G. (Frank), Rosendaal, F.R. (Frits), Garcia-Pagan, J.C. (Juan Carlos), Valla, D.C. (Dominique Charle), and Janssen, H.L.A. (Harry)

Abstract

Background: The Budd-Chiari syndrome (BCS) is hepatic venous outflow obstruction. What is known about the syndrome is based on small studies of prevalent cases. Objective: To characterize the causes and treatment of incident BCS. Design: Consecutive case series of patients with incident BCS, enrolled from October 2003 to October 2005 and followed until May 2006. Setting: Academic and nonacademic hospitals in France, Spain, Italy, Great Britain, Germany, Belgium, the Netherlands, Portugal, and Switzerland. Patients: Persons older than 16 years with definite hepatic outflow obstruction diagnosed by imaging. Persons with hepatic outflow obstruction due to heart failure, sinusoidal obstruction syndrome, cancer, or liver transplantation were excluded. Measurements: Signs and symptoms; laboratory and imaging findings; diagnosis; treatment; and overall, transplantation-free, and intervention-free survival. Results: 163 incident cases of BCS were identified. Median follow-up was 17 months (range, 0.1 to 31 months). Most patients (84%) had at least 1 thrombotic risk factor, and many (46%) had more than 1; the most common was myeloproliferative disorders (49% of 103 tested patients). Patients were mainly treated with anticoagulation (140 patients [86%]), transjugular intrahepatic portosystemic shunting (56 patients [34%]), or liver transplantation (20 patients [12%]), and 80 patients (49%) were managed noninvasively. Only 3 patients underwent surgical shunting. The survival rate was 87% (95% CI, 82% to 93%) at 1 year and 82% (CI, 75% to 88%) at 2 years. Limitation: Treatment was not standardized across all centers, and data on important clinical variables were missing for some patients. Conclusion: Most patients with BCS have at least 1 thrombotic risk factor, and many have more than 1; myeloproliferative disorders are most common. One- and 2-year survival rates are good with contemporary management, which includes noninvasive therapies (anticoagulation and diuretics) and inv

Published
2009

12. Genotype-guided dosing of coumarin derivatives: the European pharmacogenetics of anticoagulant therapy (EU-PACT) trial design

Author

Schie, R.F.M. (Rianne) van, Wadelius, M. (Mia), Kamali, F. (Farhad), Daly, A.K. (Ann), Manolopoulos, V.G. (Vangelis), Boer, A.C. (Anton) de, Barallon, R. (Rita), Verhoef, T.I. (Talitha), Kirchheiner, J. (Julia), Haschke-Becher, E. (Elisabeth), Briz, M. (Montserrat), Rosendaal, F.R. (Frits), Redekop, W.K. (Ken), Pirmohamed, M. (Munir), Maitland-van der Zee, A-H. (Anke-Hilse), Schie, R.F.M. (Rianne) van, Wadelius, M. (Mia), Kamali, F. (Farhad), Daly, A.K. (Ann), Manolopoulos, V.G. (Vangelis), Boer, A.C. (Anton) de, Barallon, R. (Rita), Verhoef, T.I. (Talitha), Kirchheiner, J. (Julia), Haschke-Becher, E. (Elisabeth), Briz, M. (Montserrat), Rosendaal, F.R. (Frits), Redekop, W.K. (Ken), Pirmohamed, M. (Munir), and Maitland-van der Zee, A-H. (Anke-Hilse)

Abstract

The narrow therapeutic range and wide interpatient variability in dose requirement make anticoagulation response to coumarin derivatives unpredictable. As a result, patients require frequent monitoring to avert adverse effects and maintain therapeutic efficacy. Polymorphisms in VKORC1 and CYP2C9 jointly account for about 40% of the interindividual

Published
2009
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13. The effect of genetic variants in the thrombin activatable fibrinolysis inhibitor (TAFI) gene on TAFI-antigen levels, clot lysis time and the risk of venous thrombosis

Author

Martini, C.H. (C.), Brandts, A. (A.), Bruijne, E.L.E. de, Hylckama Vlieg, A. (Astrid) van, Leebeek, F.W.G. (Frank), Lisman, T. (Ton), Rosendaal, F.R. (Frits), Martini, C.H. (C.), Brandts, A. (A.), Bruijne, E.L.E. de, Hylckama Vlieg, A. (Astrid) van, Leebeek, F.W.G. (Frank), Lisman, T. (Ton), and Rosendaal, F.R. (Frits)

Abstract

Thrombin activatable fibrinolysis inhibitor (TAFI) is an important inhibitor of fibrinolysis. High TAFI antigen levels are associated with an increased risk of deep venous thrombosis (DVT). Because TAFI levels are partly determined genetically, we assessed the association between three TAFI gene polymorphisms (-438 G/A, 505 A/G and 1040 C/T), TAFI antigen levels and clot lysis times and the risk of DVT. Carriers of the 505G allele, which is associated with lower TAFI antigen levels than the 505A allele, showed an increased risk of DVT. This indicates that the relationship between TAFI and venous thrombosis is more complex than previously suggested.

Published
2006
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14. Extrahepatic portal vein thrombosis: aetiology and determinants of survival

Author

Janssen, H.L.A. (Harry), Hansen, B.E. (Bettina), Hoek, B. (Bart) van, Rosendaal, F.R. (Frits), Haagsma, E.B. (Els), Uum, S.H. van, Nieuwkerk, C.M. van, Adang, R.P.R. (Rob), Chamuleau, R.A., Hattum, J. (Jan) van, Vleggaar, F.P. (Frank), Wijnhoud, A.D. (Annemarie), Janssen, H.L.A. (Harry), Hansen, B.E. (Bettina), Hoek, B. (Bart) van, Rosendaal, F.R. (Frits), Haagsma, E.B. (Els), Uum, S.H. van, Nieuwkerk, C.M. van, Adang, R.P.R. (Rob), Chamuleau, R.A., Hattum, J. (Jan) van, Vleggaar, F.P. (Frank), and Wijnhoud, A.D. (Annemarie)

Abstract

BACKGROUND: Malignancy, hypercoagulability, and conditions leading to decreased portal flow have been reported

Published
2001

15. Factor V Leiden mutation, prothrombin gene mutation, and deficiencies in coagulation inhibitors associated with Budd-Chiari syndrome and portal vein thrombosis: results of a case-control study

Author

Janssen, H.L.A. (Harry), Vandenbroucke, J.P. (Jan), Rosendaal, F.R. (Frits), Hoek, B. (Bart) van, Meinardi, J.R., Vleggaar, F.P. (Frank), Uum, S.H. van, Haagsma, E.B. (Els), Meer, F.J.M. (Felix) van der, Hattum, J. (Jan) van, Chamuleau, R.A., Adang, R.P.R. (Rob), Janssen, H.L.A. (Harry), Vandenbroucke, J.P. (Jan), Rosendaal, F.R. (Frits), Hoek, B. (Bart) van, Meinardi, J.R., Vleggaar, F.P. (Frank), Uum, S.H. van, Haagsma, E.B. (Els), Meer, F.J.M. (Felix) van der, Hattum, J. (Jan) van, Chamuleau, R.A., and Adang, R.P.R. (Rob)

Abstract

In a collaborative multicenter case-control study, we investigated the effect of factor V Leiden mutation, prothrombin gene mutation, and inherited deficiencies of protein C, protein S, and antithrombin on the risk of Budd-Chiari syndrome (BCS) and portal vein thrombosis (PVT). We compared 43 BCS patients and 92 PVT patients with 474 population-based controls. The relative risk of BCS was 11.3 (95% CI 4.8-26.5) for individuals with factor V Leiden mutation, 2.1(95% CI 0.4-9.6) for those with prothrombin gene mutation, and 6.8 (95% CI 1.9-24.4) for those with protein C deficiency. The relative risk of PVT was 2.7 (95% CI 1.1-6.9) for individuals with factor V Leiden mutation, 1.4 (95% CI 0.4-5.2) for

Published
2000

16. Optimal intensity of oral anticoagulant therapy after myocardial infarction

Author

Azar, A.J. (Aida), Cannegieter, S.C. (Suzanne), Deckers, J.W. (Jaap), Briët, E. (Ernest), Bergen, P.F.M.M. (Paul F. M.) van, Jonker, J.J.C. (Jan), Rosendaal, F.R. (Frits), Azar, A.J. (Aida), Cannegieter, S.C. (Suzanne), Deckers, J.W. (Jaap), Briët, E. (Ernest), Bergen, P.F.M.M. (Paul F. M.) van, Jonker, J.J.C. (Jan), and Rosendaal, F.R. (Frits)

Published
1996
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