38 results on '"Jukema JW"'
Search Results
2. Elucidating mechanisms of genetic cross-disease associations at the PROCR vascular disease locus (vol 13, 1222, 2022)
- Author
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Stacey, D, Chen, LY, Stanczyk, PJ, Howson, JMM, Mason, AM, Burgess, S, MacDonald, S, Langdown, J, McKinney, H, Downes, K, Farahi, N, Peters, JE, Basu, S, Pankow, JS, Tang, WH, Pankratz, N, Sabater-Lleal, M, de Vries, PS, Smith, NL, Dehghan, A, Heath, AS, Morrison, AC, Reiner, AP, Johnson, A, Richmond, A, Peters, A, Vlieg, AV, McKnight, B, Psaty, BM, Hayward, C, Ward-Caviness, C, O'Donnell, C, Chasman, D, Strachan, DP, Tregouet, DA, Mook-Kanamori, D, Gill, D, Thibord, F, Asselbergs, FW, Leebeek, FWG, Rosendaal, FR, Davies, G, Homuth, G, Temprano, G, Campbell, H, Taylor, HA, Bressler, J, Huffman, JE, Rotter, JI, Yao, J, Wilson, JF, Bis, JC, Hahn, JM, Desch, KC, Wiggins, KL, Raffield, LM, Bielak, LF, Yanek, LR, Kleber, ME, Mueller, M, Kavousi, M, Mangino, M, Conomos, MP, Liu, ML, Brown, MR, Jhun, MA, Chen, MH, de Maat, MPM, Peyser, PA, Elliot, P, Wei, P, Wild, PS, Morange, PE, van der Harst, P, Yang, Q, Le, NQ, Marioni, R, Li, RF, Damrauer, SM, Cox, SR, Trompet, S, Felix, SB, Volker, U, Koenig, W, Jukema, JW, Guo, XQ, Gelinas, AD, Schneider, DJ, Janjic, N, Samani, NJ, Ye, S, Summers, C, Chilvers, ER, Danesh, J, and Paul, DS
- Published
- 2022
3. Genome-wide association study of circulating interleukin 6 levels identifies novel loci
- Author
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Ahluwalia, TS, Prins, BP, Abdollahi, M, Armstrong, NJ, Aslibekyan, S, Bain, L, Jefferis, B, Baumert, J, Beekman, M, Ben-Shlomo, Y, Bis, JC, Mitchell, BD, de Geus, E, Delgado, GE, Marek, D, Eriksson, J, Kajantie, E, Kanoni, S, Kemp, JP, Lu, C, Marioni, RE, McLachlan, S, Milaneschi, Y, Nolte, IM, Petrelis, AM, Porcu, E, Sabater-Lleal, M, Naderi, E, Seppala, I, Shah, T, Singhal, G, Standl, M, Teumer, A, Thalamuthu, A, Thiering, E, Trompet, S, Ballantyne, CM, Benjamin, EJ, Casas, JP, Toben, C, Dedoussis, G, Deelen, J, Durda, P, Engmann, J, Feitosa, MF, Grallert, H, Hammarstedt, A, Harris, SE, Homuth, G, Hottenga, JJ, Jalkanen, S, Jamshidi, Y, Jawahar, MC, Jess, T, Kivimaki, M, Kleber, ME, Lahti, J, Liu, Y, Marques-Vidal, P, Mellstrom, D, Mooijaart, SP, Muller-Nurasyid, M, Penninx, B, Revez, JA, Rossing, P, Raikkonen, K, Sattar, N, Scharnagl, H, Sennblad, B, Silveira, A, St Pourcain, B, Timpson, NJ, Trollor, J, van Dongen, J, Van Heemst, D, Visvikis-Siest, S, Vollenweider, P, Volker, U, Waldenberger, M, Willemsen, G, Zabaneh, D, Morris, RW, Arnett, DK, Baune, BT, Boomsma, DI, Chang, YPC, Deary, IJ, Deloukas, P, Eriksson, JG, Evans, DM, Ferreira, MA, Gaunt, T, Gudnason, V, Hamsten, A, Heinrich, J, Hingorani, A, Humphries, SE, Jukema, JW, Koenig, W, Kumari, M, Kutalik, Z, Lawlor, DA, Lehtimaki, T, Marz, W, Mather, KA, Naitza, S, Nauck, M, Ohlsson, C, Price, JF, Raitakari, O, Rice, K, Sachdev, PS, Slagboom, E, Sorensen, TIA, Spector, T, Stacey, D, Stathopoulou, MG, Tanaka, T, Wannamethee, SG, Whincup, P, Rotter, JI, Dehghan, A, Boerwinkle, E, Psaty, BM, Snieder, H, Alizadeh, BZ, and CHARGE Inflammation Working Grp
- Abstract
Interleukin 6 (IL-6) is a multifunctional cytokine with both pro- and anti-inflammatory properties with a heritability estimate of up to 61%. The circulating levels of IL-6 in blood have been associated with an increased risk of complex disease pathogenesis. We conducted a two-staged, discovery and replication meta genome-wide association study (GWAS) of circulating serum IL-6 levels comprising up to 67428 (n(discovery)=52654 and n(replication)=14774) individuals of European ancestry. The inverse variance fixed effects based discovery meta-analysis, followed by replication led to the identification of two independent loci, IL1F10/IL1RN rs6734238 on chromosome (Chr) 2q14, (P-combined=1.8x10(-11)), HLA-DRB1/DRB5 rs660895 on Chr6p21 (P-combined=1.5x10(-10)) in the combined meta-analyses of all samples. We also replicated the IL6R rs4537545 locus on Chr1q21 (P-combined=1.2x10(-122)). Our study identifies novel loci for circulating IL-6 levels uncovering new immunological and inflammatory pathways that may influence IL-6 pathobiology.
- Published
- 2021
4. Evacetrapib and Cardiovascular Outcomes in High-Risk Vascular Disease
- Author
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Lincoff, A. Michael, Nicholls, Stephen J., Riesmeyer, Jeffrey S., Barter, Philip J., Brewer, H. Bryan, Fox, Keith A. A., Gibson, C. Michael, Granger, Christopher, Menon, Venu, Montalescot, Gilles, Rader, Daniel, Tall, Alan R., McErlean, Ellen, Wolski, Kathy, Ruotolo, Giacomo, Vangerow, Burkhard, Weerakkody, Govinda, Goodman, Shaun G., Conde, Diego, McGuire, Darren K., Nicolau, Jose C., Leiva-Pons, Jose L., Pesant, Yves, Li, Weimin, Kandath, David, Kouz, Simon, Tahirkheli, Naeem, Mason, Denise, Nissen, Steven E. Del Valle M, Finnell JB, Standley J, Poi K, Croaning J, Tong YC, Guerra JL, Guasparini G, Hubert C, Ardissino D, Betteridge J, Borghi C, Bruckert E, Chiang CE, Cinteza M, Dalby AJ, Erlinge D, Fernandez-Ortiz A, Ge J, Gottlieb S, Goudev A, Gratsiansky N, Huber K, Ilavská A, Jeong MH, Jukema JW, Katus H, Keltai M, Krum H, Nielsen H, Ogawa H, Ongen Z, Parkhomenko A, Raugaliene R, Renkin J, Rynkiewicz A, Steinhubl S, White H, Widimsky P, Zhu J, Armstrong P, Ridker P, Mahaffey K, Steg G, Wittes J, Bhargava A, Chenier M, Coleman C, Cremer P, Jellis C, Lahoud R, Lappe J, Min D, Monteleone P, Newton D, Stegman B, Senn T, Katzan I, Sharma J, Uchino K, Vora N, Brown K, Fabec D, Piper P, Preston S, Colombo T, Pagel-Langenickel I, Penev P, Maixing A, Crowley K, Sarkar S, Torosyan N, Castano L, Tran D, Dena V, Blain L, Keenan G, Slade K, Quinlan E, Edwards R, Ren H, Glenny J, Maffei L, Albisu Di Gennaro J, Caccavo A, Prado A, Colombo H, Luquez H, Lobo Marquez L, Hammett C, Blombery P, Colquhoun D, Amerena J, Howes L, Cooke D, Simpson R, Horowitz J, Sullivan D, Proietto J, Yeo W, Hirschl M, Hanusch U, Drexel H, Brodmann M, Wollaert B, De Wolf L, Delforge M, Vanwelden J, Peeters A, Siqueira Bodart J, Montenegro R, Franken M, Eliaschewitz F, Parvanova Z, Raev D, Mincheva V, Kichukov K, Stoyanov M, Apostolova E, Tzekova M, Dimov B, Lazov P, Devedzhiev T, Dion D, Poirier P, Lavoie JP, Lonn E, Shukla D, Chehayeb R, Nault P, Gaudet D, Tardif JC, Beaudry Y, Bakbak A, Wong B, St-Maurice F, Labonte R, Polasek P, Sweet M, Bhargava R, Nawaz S, Pandey S, Tishler S, Peterson S, O’Keefe D, Genest J, Syan R, Leiter L, Li H, Ma W, Ma C, Xu D, Li X, Hala T, Machova V, Smejkalova O, Vodnansky P, Reichert P, Velimsky T, Matuska J, Machkova M, Jerabek O, Kuchar J, Rasmussen T, Lindgren L, Alexandersen P, Bang L, Brønnum-Schou J, Valter I, Soots M, Lanno R, Rosenthal S, Cottin Y, Elbaz M, Lafitte S, Silvain J, Coste P, Rangé G, Gosse P, Morel O, Berrouschot J, Bourhaial H, Toursarkissian N, Appel KF, Rieker W, Stellbrink C, Münzel T, Geisler T, Kadel C, Giannitsis E, Trenk D, vom Dahl J, Dorsel T, Singer O, Schäufele T, Natour M, Ozaki R, Lau E, Chan K, Yeung V, Yu C, Lakatos F, Zólyomi S, Vangel S, Merkely B, Szakal I, Sipos A, Laszloczky A, Kis E, Szocs A, Szántai G, Faludi P, Kancz S, Oroszlan T, Hamoud S, Francis A, Chorin E, Leibowitz D, Kracoff O, Weisz G, Schiff E, Bitzur R, Hussein O, Di Lorenzo L, Visona A, Mos L, De Luca G, Salvioni A, Rubba P, Imberti D, Bucci M, Saku K, Sueyoshi A, Ohshima K, Kazatani Y, Shimizu M, Fujii K, Higa N, Kawamitsu K, Shimomura H, Hoshizaki H, Tashiro H, Baden M, Ueda O, Tanabe J, Momiyama Y, Hosokawa S, Takahashi N, Kimura K, Fujinaga H, Masutani M, Kuramochi T, Higashikata T, Ichikawa S, Yamagishi M, Sakota S, Sakuragi S, Suzuki M, Taguchi S, Nakamura T, Ozaki Y, Tsujita K, Yasuda S, Ando K, Fujimoto K, Tanabe K, Fukunaga M, Kavaliauskiene R, Motiejuniene L, Slapikas R, Jarasuniene D, De los Rios Ibarra M, Alcocer Gamba M, Nevarez Ruiz L, Fajardo-Campos P, Llamas Esperon G, Violante Ortiz R, Stobschinski de Alba C, Guizar Sanchez C, Guerra Lopez A, Montano E, Miracle S, Fanghanel G, Lenderink T, Troquay R, Van Leendert R, van Eck J, Hamer B, Ronner E, Karalis I, Lok D, Magro M, Westendorp I, Stroes E, De Melker E, Verhave G, Plomp J, Bronzwaer P, Wiersma J, Kooy A, Herrman JP, Imholz B, de Groot M, Devlin G, Elliott J, Benatar J, Harding S, Hart H, Young C, Mirek-Bryniarska E, Gniot J, Broncel M, Kozina M, Kus W, Sciborski R, Lesnik J, Kawka-Urbanek T, Krzyzanowski M, Okopien B, Wierzbicka K, Dyczek A, Ochean V, Copaci I, Matei C, Pruna C, Constantinescu M, Minescu B, Stamate C, Boldueva S, Markov V, Alexeeva N, Chizhov P, Supryadkina T, Petrochenkova N, Zrazhevsky K, Barbarash O, Gurevich V, Hranai M, Gergel V, Dzupina A, Uhliar R, Vinanska D, Fazekas F, Bugan W, Saaiman J, Nortje H, Theron H, Bernhardi D, Ramlachan P, Van-Zyl L, Basson M, Venter T, Kim D, Han S, Park G, Hwang K, Rhee M, Cho B, Jeong J, Hong B, Chang K, Garcia Puig J, Fuentes Jiménez F, Nieto Iglesias LJ, Pintó Sala X, Gamez JM, Sánchez Álvarez J, Hernandez García JM, Olsson A, Mooe T, Tengmark BO, Lindholm CJ, Hansen O, Tyden P, Moccetti T, Binder R, Ueng K, Lai W, Shyu K, Hsieh I, Sheu W, Chen J, Altunkeser B, Erkan A, Karpenko O, Kaydashev I, Yagensky A, Kovalenko V, Brunskill J, Barr C, Cecil J, Cahill T, A Gorog D, Bakhai A, Coulson W, Gorog D, Loftus I, Haddad T, Hotchkiss D, Isserman S, Janik M, Weinstein D, Wilson S, Butman S, Hearne S, Khan F, Nadar V, Zelman R, Benton R, Flores E, Kahn B, Soni A, Asbill B, Singal D, Dy J, Foucauld J, Crenshaw B, Rogers W, Aslam A, Lieber I, Shah P, Durr S, Spencer R, Mahal S, Cheng S, Abadier R, Gilmore R, Staniloae C, Miller G, Seals A, Jetty P, Mathis C, Henry S, Murray A, Felten W, Navas J, Gudipati R, Singh N, West S, Sabatino K, Crater T, Amin J, Dosh K, Earl J, Z Jafar M, Gelernt M, Kutner M, Salazar J, Krantzler J, El-Ahdab F, Lader E, Zakhary B, Miller S, Madder R, Khan T, Khan M, Collis W, Evans J, Prodafikas J, Panchal V, Cohen K, Weiss R, Dietrich D, Vogel C, Mascarenhas V, Seaworth J, Teklinski A, Davalos J, Dehning M, Herzog W, Snyder H, Talano J, Donahoe S, Hunter J, Sandoval J, Batchelor W, Brautigam D, Moriarty K, Siachos A, Kereiakes D, Traboulssi M, Arif I, Kosinski E, Quadrel M, DeHart D, Miller M, Poock J, Loh I, van Cleeff M, Georgeson S, Suryanarayana P, Cohn J, Schmedtje J, Lamas G, DeSantis J, Stahl L, Prashad R, Schuchard T, Schramm E, Rao V, Deen C, Soufer J, Gurbel P, Vazquez-Tanus J, Srivastava S, Ballantyne C, Lotun K, Younis L, Gupta D, Yeoman G, Zebrack J, Knutson T, Whitaker J, Appel M, Koren M, Muneer B, Fairlamb J, Aviles R, Kozlowski L, Rees A, Stephens M, Mays M, Downey H, Almassi H, Peichert D, Rocco M, French W, Bhatia P, Hoch J, Peart B, Carmichael P, Acheatel R, Vo A, Kirtane A, Bhagwat R, Gilchrist I, Labroo A, Pollock S, Bacon J, Karunaratne H, Moursi M, Doshi A, Sethi P, Treasure C, Marple R, Goodwin T, Zayas-Torres C, Loussararian A, Korn D, Paster R, Albirini A, Moretto T, Guarnieri T, White L, Kramer J, Shortal B, Maynard K, Raikhel M, Rohatgi A, Melucci M, Masri B, Krichmar P, Morris F, Canto J, Wali A, Comerota A, Ellison W, Degregorio M, Chandrika Parameswaran A, Goldscher D, George W, Mulkay A, Maynard R, Ziada K, Strain J, Hermiller J, Ennis B, Desai V, Al-Joundi B, Azocar J, Claudio J, Perez Vargas E, Loy J, Albert M, Chandler G, Maislos F, Graf R, Rama P, Studeny M, Gimple L, Pytlewski G, Simon H, Islam A, Dillon W, Shah S, Geohas C., Lincoff, Am, Nicholls, Sj, Riesmeyer, J, Barter, Pj, Brewer, Hb, Fox, Kaa, Gibson, Cm, Granger, C, Menon, V, Montalescot, G, Rader, D, Tall, Ar, Mcerlean, E, Wolski, K, Ruotolo, G, Vangerow, B, Weerakkody, G, Goodman, Sg, Conde, D, Mcguire, Dk, Nicolau, Jc, Leiva-Pons, Jl, Pesant, Y, Li, W, Kandath, D, Kouz, S, Tahirkheli, N, Mason, D, Nissen, Se, Del Valle, M, Finnell, Jb, Standley, J, Poi, K, Croaning, J, Tong, Yc, Guerra, Jl, Guasparini, G, Hubert, C, Ardissino, D, Betteridge, J, Borghi, C, Bruckert, E, Chiang, Ce, Cinteza, M, Dalby, Aj, Erlinge, D, Fernandez-Ortiz, A, Ge, J, Gottlieb, S, Goudev, A, Gratsiansky, N, Huber, K, Ilavská, A, Jeong, Mh, Jukema, Jw, Katus, H, Keltai, M, Krum, H, Nielsen, H, Ogawa, H, Ongen, Z, Parkhomenko, A, Raugaliene, R, Renkin, J, Rynkiewicz, A, Steinhubl, S, White, H, Widimsky, P, Zhu, J, Armstrong, P, Ridker, P, Mahaffey, K, Steg, G, Wittes, J, Bhargava, A, Chenier, M, Coleman, C, Cremer, P, Jellis, C, Lahoud, R, Lappe, J, Min, D, Monteleone, P, Newton, D, Stegman, B, Senn, T, Katzan, I, Sharma, J, Uchino, K, Vora, N, Brown, K, Fabec, D, Piper, P, Preston, S, Colombo, T, Pagel-Langenickel, I, Penev, P, Maixing, A, Crowley, K, Sarkar, S, Torosyan, N, Castano, L, Tran, D, Dena, V, Blain, L, Keenan, G, Slade, K, Quinlan, E, Edwards, R, Ren, H, Glenny, J, Maffei, L, Albisu Di Gennaro, J, Caccavo, A, Prado, A, Colombo, H, Luquez, H, Lobo Marquez, L, Hammett, C, Blombery, P, Colquhoun, D, Amerena, J, Howes, L, Cooke, D, Simpson, R, Horowitz, J, Sullivan, D, Proietto, J, Yeo, W, Hirschl, M, Hanusch, U, Drexel, H, Brodmann, M, Wollaert, B, De Wolf, L, Delforge, M, Vanwelden, J, Peeters, A, Siqueira Bodart, J, Montenegro, R, Franken, M, Eliaschewitz, F, Parvanova, Z, Raev, D, Mincheva, V, Kichukov, K, Stoyanov, M, Apostolova, E, Tzekova, M, Dimov, B, Lazov, P, Devedzhiev, T, Dion, D, Poirier, P, Lavoie, Jp, Lonn, E, Shukla, D, Chehayeb, R, Nault, P, Gaudet, D, Tardif, Jc, Beaudry, Y, Bakbak, A, Wong, B, St-Maurice, F, Labonte, R, Polasek, P, Sweet, M, Bhargava, R, Nawaz, S, Pandey, S, Tishler, S, Peterson, S, O’Keefe, D, Genest, J, Syan, R, Leiter, L, Li, H, Ma, W, Ma, C, Xu, D, Li, X, Hala, T, Machova, V, Smejkalova, O, Vodnansky, P, Reichert, P, Velimsky, T, Matuska, J, Machkova, M, Jerabek, O, Kuchar, J, Rasmussen, T, Lindgren, L, Alexandersen, P, Bang, L, Brønnum-Schou, J, Valter, I, Soots, M, Lanno, R, Rosenthal, S, Cottin, Y, Elbaz, M, Lafitte, S, Silvain, J, Coste, P, Rangé, G, Gosse, P, Morel, O, Berrouschot, J, Bourhaial, H, Toursarkissian, N, Appel, Kf, Rieker, W, Stellbrink, C, Münzel, T, Geisler, T, Kadel, C, Giannitsis, E, Trenk, D, vom Dahl, J, Dorsel, T, Singer, O, Schäufele, T, Natour, M, Ozaki, R, Lau, E, Chan, K, Yeung, V, Yu, C, Lakatos, F, Zólyomi, S, Vangel, S, Merkely, B, Szakal, I, Sipos, A, Laszloczky, A, Kis, E, Szocs, A, Szántai, G, Faludi, P, Kancz, S, Oroszlan, T, Hamoud, S, Francis, A, Chorin, E, Leibowitz, D, Kracoff, O, Weisz, G, Schiff, E, Bitzur, R, Hussein, O, Di Lorenzo, L, Visona, A, Mos, L, De Luca, G, Salvioni, A, Rubba, P, Imberti, D, Bucci, M, Saku, K, Sueyoshi, A, Ohshima, K, Kazatani, Y, Shimizu, M, Fujii, K, Higa, N, Kawamitsu, K, Shimomura, H, Hoshizaki, H, Tashiro, H, Baden, M, Ueda, O, Tanabe, J, Momiyama, Y, Hosokawa, S, Takahashi, N, Kimura, K, Fujinaga, H, Masutani, M, Kuramochi, T, Higashikata, T, Ichikawa, S, Yamagishi, M, Sakota, S, Sakuragi, S, Suzuki, M, Taguchi, S, Nakamura, T, Ozaki, Y, Tsujita, K, Yasuda, S, Ando, K, Fujimoto, K, Tanabe, K, Fukunaga, M, Kavaliauskiene, R, Motiejuniene, L, Slapikas, R, Jarasuniene, D, De los Rios Ibarra, M, Alcocer Gamba, M, Nevarez Ruiz, L, Fajardo-Campos, P, Llamas Esperon, G, Violante Ortiz, R, Stobschinski de Alba, C, Guizar Sanchez, C, Guerra Lopez, A, Montano, E, Miracle, S, Fanghanel, G, Lenderink, T, Troquay, R, Van Leendert, R, van Eck, J, Hamer, B, Ronner, E, Karalis, I, Lok, D, Magro, M, Westendorp, I, Stroes, E, De Melker, E, Verhave, G, Plomp, J, Bronzwaer, P, Wiersma, J, Kooy, A, Herrman, Jp, Imholz, B, de Groot, M, Devlin, G, Elliott, J, Benatar, J, Harding, S, Hart, H, C, Young, Mirek-Bryniarska, E, Gniot, J, Broncel, M, Kozina, M, Kus, W, Sciborski, R, Lesnik, J, Kawka-Urbanek, T, Krzyzanowski, M, Okopien, B, Wierzbicka, K, Dyczek, A, Ochean, V, Copaci, I, Matei, C, Pruna, C, Constantinescu, M, Minescu, B, Stamate, C, Boldueva, S, Markov, V, Alexeeva, N, Chizhov, P, Supryadkina, T, Petrochenkova, N, Zrazhevsky, K, Barbarash, O, Gurevich, V, Hranai, M, Gergel, V, Dzupina, A, Uhliar, R, Vinanska, D, Fazekas, F, Bugan, W, Saaiman, J, Nortje, H, Theron, H, Bernhardi, D, Ramlachan, P, Van-Zyl, L, Basson, M, Venter, T, Kim, D, Han, S, Park, G, Hwang, K, Rhee, M, Cho, B, Jeong, J, Hong, B, Chang, K, Garcia Puig, J, Fuentes Jiménez, F, Nieto Iglesias LJ, Pintó Sala, X, Gamez, Jm, Sánchez Álvarez, J, Hernandez García JM, Olsson, A, Mooe, T, Tengmark, Bo, Lindholm, Cj, Hansen, O, Tyden, P, Moccetti, T, Binder, R, Ueng, K, Lai, W, Shyu, K, Hsieh, I, Sheu, W, Chen, J, Altunkeser, B, Erkan, A, Karpenko, O, Kaydashev, I, Yagensky, A, Kovalenko, V, Brunskill, J, Barr, C, Cecil, J, Cahill, T, A Gorog D, Bakhai, A, Coulson, W, Gorog, D, Loftus, I, Haddad, T, Hotchkiss, D, Isserman, S, Janik, M, Weinstein, D, Wilson, S, Butman, S, Hearne, S, Khan, F, Nadar, V, Zelman, R, R, Benton, E, Flore, Kahn, B, Soni, A, Asbill, B, Singal, D, Dy, J, Foucauld, J, Crenshaw, B, Rogers, W, Aslam, A, Lieber, I, Shah, P, Durr, S, Spencer, R, Mahal, S, Cheng, S, Abadier, R, Gilmore, R, Staniloae, C, Miller, G, Seals, A, Jetty, P, Mathis, C, Henry, S, Murray, A, Felten, W, Navas, J, Gudipati, R, Singh, N, West, S, Sabatino, K, Crater, T, Amin, J, Dosh, K, Earl, J, Z Jafar M, Gelernt, M, Kutner, M, J, Salazar, Krantzler, J, El-Ahdab, F, Lader, E, Zakhary, B, Miller, S, Madder, R, Khan, T, Khan, M, Collis, W, Evans, J, Prodafikas, J, Panchal, V, Cohen, K, Weiss, R, Dietrich, D, Vogel, C, Mascarenhas, V, Seaworth, J, Teklinski, A, Davalos, J, Dehning, M, Herzog, W, Snyder, H, Talano, J, Donahoe, S, Hunter, J, Sandoval, J, Batchelor, W, Brautigam, D, Moriarty, K, Siachos, A, Kereiakes, D, Traboulssi, M, Arif, I, Kosinski, E, Quadrel, M, Dehart, D, Miller, M, Poock, J, Loh, I, van Cleeff, M, Georgeson, S, Suryanarayana, P, Cohn, J, Schmedtje, J, Lamas, G, Desantis, J, Stahl, L, Prashad, R, Schuchard, T, Schramm, E, Rao, V, Deen, C, Soufer, J, Gurbel, P, Vazquez-Tanus, J, Srivastava, S, Ballantyne, C, Lotun, K, Younis, L, Gupta, D, Yeoman, G, Zebrack, J, Knutson, T, Whitaker, J, Appel, M, Koren, M, Muneer, B, Fairlamb, J, Aviles, R, Kozlowski, L, Rees, A, Stephens, M, Mays, M, Downey, H, Almassi, H, Peichert, D, Rocco, M, French, W, Bhatia, P, Hoch, J, Peart, B, Carmichael, P, Acheatel, R, Vo, A, Kirtane, A, Bhagwat, R, Gilchrist, I, Labroo, A, Pollock, S, Bacon, J, Karunaratne, H, Moursi, M, Doshi, A, Sethi, P, Treasure, C, Marple, R, Goodwin, T, Zayas-Torres, C, Loussararian, A, Korn, D, Paster, R, Albirini, A, Moretto, T, Guarnieri, T, White, L, Kramer, J, Shortal, B, Maynard, K, Raikhel, M, Rohatgi, A, Melucci, M, Masri, B, Krichmar, P, Morris, F, Canto, J, Wali, A, Comerota, A, Ellison, W, Degregorio, M, Chandrika Parameswaran, A, Goldscher, D, George, W, Mulkay, A, Maynard, R, Ziada, K, Strain, J, Hermiller, J, Ennis, B, Desai, V, Al-Joundi, B, Azocar, J, Claudio, J, Perez Vargas, E, Loy, J, Albert, M, Chandler, G, Maislos, F, Graf, R, Rama, P, Studeny, M, Gimple, L, Pytlewski, G, Simon, H, Islam, A, Dillon, W, Shah, S, Geohas, C., Lincoff, A. Michael, Nicholls, Stephen J., Riesmeyer, Jeffrey S., Barter, Philip J., Brewer, H. Bryan, Fox, Keith A. A., Gibson, C. Michael, Granger, Christopher, Menon, Venu, Montalescot, Gille, Rader, Daniel, Tall, Alan R., Mcerlean, Ellen, Wolski, Kathy, Ruotolo, Giacomo, Vangerow, Burkhard, Weerakkody, Govinda, Goodman, Shaun G., Conde, Diego, Mcguire, Darren K., Nicolau, Jose C., Leiva-Pons, Jose L., Pesant, Yve, Li, Weimin, Kandath, David, Kouz, Simon, Tahirkheli, Naeem, Mason, Denise, Nissen, Steven E., Del Valle M, Young, C, Nieto Iglesias, Lj, Hernandez García, Jm, A Gorog, D, Benton, R, Flores, E, Z Jafar, M, and Salazar, J
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Male ,0301 basic medicine ,Cardiovascular Outcome ,Cholesterol Ester Transfer Protein ,Myocardial Ischemia ,030204 cardiovascular system & hematology ,Coronary artery disease ,cholesteryl ester transfer protein inhibitor ,Benzodiazepines ,chemistry.chemical_compound ,0302 clinical medicine ,Cardiovascular Disease ,Anticholesteremic Agent ,Intracranial Arteriosclerosi ,Treatment Failure ,Evacetrapib ,Peripheral Vascular Diseases ,Benzodiazepine ,biology ,Medicine (all) ,Anticholesteremic Agents ,Diabetes Mellitu ,General Medicine ,Middle Aged ,Intracranial Arteriosclerosis ,High-Risk Vascular Disease ,Editorial ,Cardiovascular Diseases ,Cardiology ,Female ,lipids (amino acids, peptides, and proteins) ,Human ,Risk ,medicine.medical_specialty ,Acute coronary syndrome ,03 medical and health sciences ,Double-Blind Method ,Internal medicine ,Diabetes mellitus ,Cholesterylester transfer protein ,Diabetes Mellitus ,Journal Article ,medicine ,Humans ,Aged ,Cholesterol ,Vascular disease ,business.industry ,Cholesterol, HDL ,Biomarker ,Cholesterol, LDL ,medicine.disease ,Cholesterol Ester Transfer Proteins ,Surgery ,030104 developmental biology ,Peripheral Vascular Disease ,chemistry ,biology.protein ,business ,Biomarkers ,Lipoprotein - Abstract
BACKGROUND: The cholesteryl ester transfer protein inhibitor evacetrapib substantially raises the high-density lipoprotein (HDL) cholesterol level, reduces the low-density lipoprotein (LDL) cholesterol level, and enhances cellular cholesterol efflux capacity. We sought to determine the effect of evacetrapib on major adverse cardiovascular outcomes in patients with high-risk vascular disease. METHODS: In a multicenter, randomized, double-blind, placebo-controlled phase 3 trial, we enrolled 12,092 patients who had at least one of the following conditions: an acute coronary syndrome within the previous 30 to 365 days, cerebrovascular atherosclerotic disease, peripheral vascular arterial disease, or diabetes mellitus with coronary artery disease. Patients were randomly assigned to receive either evacetrapib at a dose of 130 mg or matching placebo, administered daily, in addition to standard medical therapy. The primary efficacy end point was the first occurrence of any component of the composite of death from cardiovascular causes, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina. RESULTS: At 3 months, a 31.1% decrease in the mean LDL cholesterol level was observed with evacetrapib versus a 6.0% increase with placebo, and a 133.2% increase in the mean HDL cholesterol level was seen with evacetrapib versus a 1.6% increase with placebo. After 1363 of the planned 1670 primary end-point events had occurred, the data and safety monitoring board recommended that the trial be terminated early because of a lack of efficacy. After a median of 26 months of evacetrapib or placebo, a primary end-point event occurred in 12.9% of the patients in the evacetrapib group and in 12.8% of those in the placebo group (hazard ratio, 1.01; 95% confidence interval, 0.91 to 1.11; P=0.91). CONCLUSIONS: Although the cholesteryl ester transfer protein inhibitor evacetrapib had favorable effects on established lipid biomarkers, treatment with evacetrapib did not result in a lower rate of cardiovascular events than placebo among patients with high-risk vascular disease. (Funded by Eli Lilly; ACCELERATE ClinicalTrials.gov number, NCT01687998 .).
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- 2017
5. Alirocumab in Patients With Polyvascular Disease and Recent Acute Coronary Syndrome ODYSSEY OUTCOMES Trial
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Jukema, JW, Szarek, M, Zijlstra, LE (Laurien), de Silva, HA, Bhatt, DL, Bittner, VA, Simoons, Maarten, Sijbrands, E.J.G., Picault, P, Zobouyan, I, Cardiology, and Internal Medicine
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- 2019
6. GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes
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Franceschini, N, Giambartolomei, C, de Vries, PS, Finan, C, Bis, JC, Huntley, RP, Lovering, RC, Tajuddin, SM, Winkler, TW, Graff, M, Kavousi, M, Dale, C, Smith, AV, Hofer, E, van Leeuwen, EM, Nolte, IM, Lu, L, Scholz, M, Sargurupremraj, M, Pitkänen, N, Franzén, O, Joshi, PK, Noordam, R, Marioni, RE, Hwang, SJ, Musani, SK, Schminke, U, Palmas, W, Isaacs, A, Correa, A, Zonderman, AB, Hofman, A, Teumer, A, Cox, AJ, Uitterlinden, AG, Wong, A, Smit, AJ, Newman, AB, Britton, A, Ruusalepp, A, Sennblad, B, Hedblad, B, Pasaniuc, B, Penninx, BW, Langefeld, CD, Wassel, CL, Tzourio, C, Fava, C, Baldassarre, D, O’Leary, DH, Teupser, D, Kuh, D, Tremoli, E, Mannarino, E, Grossi, E, Boerwinkle, E, Schadt, EE, Ingelsson, E, Veglia, F, Rivadeneira, F, Beutner, F, Chauhan, G, Heiss, G, Snieder, H, Campbell, H, Völzke, H, Markus, HS, Deary, IJ, Jukema, JW, de Graaf, J, Price, J, Pott, J, Hopewell, JC, Liang, J, Thiery, J, Engmann, J, Gertow, K, Rice, K, Taylor, KD, Dhana, K, Kiemeney, LALM, Lind, L, Raffield, LM, Launer, LJ, Holdt, LM, Dörr, M, Dichgans, M, Traylor, M, Sitzer, M, Kumari, M, Kivimaki, M, Nalls, MA, Melander, O, Raitakari, O, Franco, OH, Rueda-Ochoa, OL, Roussos, P, Whincup, PH, Amouyel, P, and Giral, P
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Aging ,MEGASTROKE Consortium ,Quantitative Trait Loci ,ADAMTS9 Protein ,Coronary Disease ,Cardiovascular ,Polymorphism, Single Nucleotide ,Carotid Intima-Media Thickness ,Protein-Lysine 6-Oxidase ,Risk Factors ,Genetics ,2.1 Biological and endogenous factors ,Humans ,Genetic Predisposition to Disease ,cardiovascular diseases ,Aetiology ,Polymorphism ,Heart Disease - Coronary Heart Disease ,Plaque ,Atherosclerotic ,Human Genome ,Single Nucleotide ,Atherosclerosis ,Plaque, Atherosclerotic ,Brain Disorders ,Stroke ,Heart Disease ,cardiovascular system ,Amino Acid Oxidoreductases ,Lod Score ,Genome-Wide Association Study - Abstract
© 2018, The Author(s). Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans.
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- 2018
7. Serum magnesium and calcium levels in relation to ischemic stroke: Mendelian randomization study
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Larsson, SC, Traylor, M, Burgess, S, Boncoraglio, GB, Jern, C, Michaëlsson, K, Markus, HS, Malik, R, Chauhan, G, Sargurupremraj, M, Okada, Y, Mishra, A, Rutten-Jacobs, L, Giese, AK, Van Der Laan, SW, Gretarsdottir, S, Anderson, CD, Chong, M, Adams, HHH, Ago, T, Almgren, P, Amouyel, P, Ay, H, Bartz, RM, Benavente, OR, Bevan, S, Brown, RD, Butterworth, AS, Carrera, C, Carty, CL, Chasman, DI, Chen, WM, Cole, JW, Correa, A, Cotlarciuc, I, Cruchaga, C, Danesh, J, De Bakker, PIW, Destefano, AL, Hoed, MD, Duan, Q, Engelter, ST, Falcone, GJ, Gottesman, RF, Grewal, RP, Gudnason, V, Gustafsson, S, Haessler, J, Harris, TB, Hassan, A, Havulinna, AS, Heckbert, SR, Holliday, EG, Howard, G, Hsu, FC, Hyacinth, HI, Ikram, MA, Ingelsson, E, Irvin, MR, Jian, X, Jiménez-Conde, J, Johnson, JA, Jukema, JW, Kanai, M, Keene, KL, Kissela, BM, Kleindorfer, DO, Kooperberg, C, Kubo, M, Lange, LA, Langefeld, CD, Langenberg, C, Launer, LJ, Lee, JM, Lemmens, R, Leys, D, Lewis, CM, Lin, WY, Lindgren, AG, Lorentzen, E, Magnusson, PK, Maguire, J, Manichaikul, A, McArdle, PF, Meschia, JF, Mitchell, BD, Mosley, TH, Nalls, MA, Ninomiya, T, O'Donnell, MJ, Psaty, BM, Pulit, SL, Rannikmäe, K, Reiner, AP, Rexrode, KM, Rice, K, Rich, SS, Ridker, PM, Rost, NS, and Rothwell, PM
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Stroke ,Neurology & Neurosurgery ,Intracranial Embolism ,Humans ,Calcium ,Magnesium ,Mendelian Randomization Analysis ,Polymorphism, Single Nucleotide ,Brain Ischemia - Abstract
© 2019 American Academy of Neurology. ObjectiveTo determine whether serum magnesium and calcium concentrations are causally associated with ischemic stroke or any of its subtypes using the mendelian randomization approach.MethodsAnalyses were conducted using summary statistics data for 13 single-nucleotide polymorphisms robustly associated with serum magnesium (n = 6) or serum calcium (n = 7) concentrations. The corresponding data for ischemic stroke were obtained from the MEGASTROKE consortium (34,217 cases and 404,630 noncases).ResultsIn standard mendelian randomization analysis, the odds ratios for each 0.1 mmol/L (about 1 SD) increase in genetically predicted serum magnesium concentrations were 0.78 (95% confidence interval [CI] 0.69-0.89; p = 1.3 × 10-4) for all ischemic stroke, 0.63 (95% CI 0.50-0.80; p = 1.6 × 10-4) for cardioembolic stroke, and 0.60 (95% CI 0.44-0.82; p = 0.001) for large artery stroke; there was no association with small vessel stroke (odds ratio 0.90, 95% CI 0.67-1.20; p = 0.46). Only the association with cardioembolic stroke was robust in sensitivity analyses. There was no association of genetically predicted serum calcium concentrations with all ischemic stroke (per 0.5 mg/dL [about 1 SD] increase in serum calcium: odds ratio 1.03, 95% CI 0.88-1.21) or with any subtype.ConclusionsThis study found that genetically higher serum magnesium concentrations are associated with a reduced risk of cardioembolic stroke but found no significant association of genetically higher serum calcium concentrations with any ischemic stroke subtype.
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- 2018
8. Exome-chip meta-analysis identifies novel loci associated with cardiac conduction, including ADAMTS6
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Prins, Bram P, Mead, Timothy J, Brody, Jennifer A, Sveinbjornsson, Gardar, Ntalla, Ioanna, Bihlmeyer, Nathan A, van den Berg, Marten, Bork-Jensen, Jette, Cappellani, Stefania, Van Duijvenboden, Stefan, Klena, Nikolai T, Gabriel, George C, Liu, Xiaoqin, Gulec, Cagri, Grarup, Niels, Haessler, Jeffrey, Hall, Leanne M, Iorio, Annamaria, Isaacs, Aaron, Li-Gao, Ruifang, Lin, Honghuang, Liu, Ching-Ti, Lyytikäinen, Leo-Pekka, Marten, Jonathan, Mei, Hao, Müller-Nurasyid, Martina, Orini, Michele, Padmanabhan, Sandosh, Radmanesh, Farid, Ramirez, Julia, Robino, Antonietta, Schwartz, Molly, van Setten, Jessica, Smith, Albert V, Verweij, Niek, Warren, Helen R, Weiss, Stefan, Alonso, Alvaro, Arnar, David O, Bots, Michiel L, de Boer, Rudolf A, Dominiczak, Anna F, Eijgelsheim, Mark, Ellinor, Patrick T, Guo, Xiuqing, Felix, Stephan B, Harris, Tamara B, Hayward, Caroline, Heckbert, Susan R, Huang, Paul L, Jukema, JW, Kähönen, Mika, Kors, Jan A, Lambiase, Pier D, Launer, Lenore J, Li, Man, Linneberg, Allan, Nelson, Christopher P, Pedersen, Oluf, Perez, Marco, Peters, Annette, Polasek, Ozren, Psaty, Bruce M, Raitakari, Olli T, Rice, Kenneth M, Rotter, Jerome I, Sinner, Moritz F, Soliman, Elsayed Z, Spector, Tim D, Strauch, Konstantin, Thorsteinsdottir, Unnur, Tinker, Andrew, Trompet, Stella, Uitterlinden, André, Vaartjes, Ilonca, van der Meer, Peter, Völker, Uwe, Völzke, Henry, Waldenberger, Melanie, Wilson, James G, Xie, Zhijun, Asselbergs, Folkert W, Dörr, Marcus, van Duijn, Cornelia M, Gasparini, Paolo, Gudbjartsson, Daniel F, Gudnason, Vilmundur, Hansen, Torben, Kääb, Stefan, Kanters, Jørgen K, Kooperberg, Charles, Lehtimäki, Terho, Lin, Henry J, Lubitz, Steven A, Mook-Kanamori, Dennis O, Conti, Francesco J, Newton-Cheh, Christopher H, Rosand, Jonathan, Rudan, Igor, and Samani, Nilesh J
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Male ,Bioinformatics ,Gene Expression ,Black People ,Conduction ,Cardiovascular ,White People ,Mice ,Electrocardiography ,Open Reading Frames ,ADAMTS Proteins ,Heart Conduction System ,Information and Computing Sciences ,Exome Sequencing ,Genetics ,Animals ,Humans ,2.1 Biological and endogenous factors ,Exome ,Polymorphism ,Aetiology ,Myocardium ,Gene Expression Profiling ,Human Genome ,Single Nucleotide ,Middle Aged ,Biological Sciences ,Exome chip ,Meta-analysis ,Heart Disease ,Genetic Loci ,Connexin 43 ,ADAMTS6 ,Female ,Environmental Sciences ,Genome-Wide Association Study - Abstract
BackgroundGenome-wide association studies conducted on QRS duration, an electrocardiographic measurement associated with heart failure and sudden cardiac death, have led to novel biological insights into cardiac function. However, the variants identified fall predominantly in non-coding regions and their underlying mechanisms remain unclear.ResultsHere, we identify putative functional coding variation associated with changes in the QRS interval duration by combining Illumina HumanExome BeadChip genotype data from 77,898 participants of European ancestry and 7695 of African descent in our discovery cohort, followed by replication in 111,874individuals of European ancestry from the UK Biobank and deCODE cohorts. We identify ten novel loci, seven within coding regions, including ADAMTS6, significantly associated with QRS duration in gene-based analyses. ADAMTS6 encodes a secreted metalloprotease of currently unknown function. In vitro validation analysis shows that the QRS-associated variants lead to impaired ADAMTS6 secretion and loss-of function analysis in mice demonstrates a previously unappreciated role for ADAMTS6 in connexin 43 gap junction expression, which is essential for myocardial conduction.ConclusionsOur approach identifies novel coding and non-coding variants underlying ventricular depolarization and provides a possible mechanism for the ADAMTS6-associated conduction changes.
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- 2018
9. Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome
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Schwartz GG, Steg PG, Szarek M, Bhatt DL, Bittner VA, Diaz R, Edelberg JM, Goodman SG, Hanotin C, Harrington RA, Jukema JW, Lecorps G, Mahaffey KW, Moryusef A, Pordy R, Quintero K, Roe MT, Sasiela WJ, Tamby JF, Tricoci P, White HD, Zeiher AM, and ODYSSEY OUTCOMES Committees and Investigators
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- 2018
10. Glycated hemoglobin measurement and prediction of cardiovascular disease
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Emerging Risk Factors Collaboration, Di Angelantonio E, Gao P, Khan H, Butterworth AS, Wormser D, Kaptoge S, Kondapally Seshasai SR, Thompson A, Sarwar N, Willeit P, Ridker PM, Barr EL, Khaw KT, Psaty BM, Brenner H, Balkau B, Dekker JM, Lawlor DA, Daimon M, Willeit J, Njølstad I, Nissinen A, Brunner EJ, Kuller LH, Price JF, Sundström J, Knuiman MW, Feskens EJ, Verschuren WM, Wald N, Bakker SJ, Whincup PH, Ford I, Goldbourt U, Gómez de la Cámara A, Gallacher J, Simons LA, Rosengren A, Sutherland SE, Björkelund C, Blazer DG, Wassertheil Smoller S, Onat A, Marín Ibañez A, Casiglia E, Jukema JW, Simpson LM, Giampaoli S, Nordestgaard BG, Selmer R, Wennberg P, Kauhanen J, Salonen JT, Dankner R, Barrett Connor E, Kavousi M, Gudnason V, Evans D, Wallace RB, Cushman M, D'Agostino RB Sr, Umans JG, Kiyohara Y, Nakagawa H, Sato S, Gillum RF, Folsom AR, van der Schouw YT, Moons KG, Griffin SJ, Sattar N, Wareham NJ, Selvin E, Thompson SG, Danesh J. Collaborators Simpson LM, Coresh J, Wagenknecht L, Shaw JE, Zimmet PZ, Magliano D, Wannamethee SG, Morris RW, Kiechl S, Santer P, Bonora E, Casas JP, Ebrahim S, Ben Shlomo Y, Yarnell JW, Elwood P, Bachman DL, Nietert PJ, Håheim LL, Søgaard AJ, Tybjaerg Hansen A, Frikke Schmidt R, Benn M, Palmieri L, Vanuzzo D, Bonnet F, Copin N, Roussel R, Gómez Gerique JA, Rubio Herrera MA, Gutiérrez Fuentes JA, Friedlander Y, McCallum J, Simons J, Lee AJ, McLachlan S, Taylor JO, Guralnik JM, Phillips CL, Evans DA, Kohout F, Cohen H, George L, Fillenbaum G, McGloin JM, Khaw K., Schöttker B, Müller H, Rothenbacher D, Jansson J., Hallmans G, Tuomilehto J, Donfrancesco C, Woodward M, Oizumi T, Kayama T, Kato T, Danker R, Chetrit A, Wilhelmsen L, Eriksson H, Lappas G, Bengtsson C, Lissner L, Skoog I, Cremer P, Arima H, Ninomiya T, Hata J, Nijpels G, Stehouwer CD, Tuomainen T., Voutilainen S, Kurl S, de Boer IH, Bertoni AG, Veschuren WM, Dullaart RP, Lambers Heerspink HJ, Hilege HL, Trompet S, Stott DJ, Dagenais GR, Cantin B, Dehghan D, Hofman A, Franco OH, Tunstall Pedoe H, Lee E, Best L, Howard BV, Can G, Ademoğlu E, Sakurai M, Nakamura K, Morikawa Y, Løchen M., Mathiesen EB, Wilsgaard T, Byberg L, Cederholm T, Olsson E, Pradhan AD, Cook NR, Kromhout D, Walker M, Watson S, Burgess S, Gregson J, Harshfield E, Pennells L, Spackman S, Warnakula S, Wood AM, Danesh J., PANICO, SALVATORE, Emerging Risk Factors, Collaboration, Di Angelantonio, E, Gao, P, Khan, H, Butterworth, A, Wormser, D, Kaptoge, S, Kondapally Seshasai, Sr, Thompson, A, Sarwar, N, Willeit, P, Ridker, Pm, Barr, El, Khaw, Kt, Psaty, Bm, Brenner, H, Balkau, B, Dekker, Jm, Lawlor, Da, Daimon, M, Willeit, J, Njølstad, I, Nissinen, A, Brunner, Ej, Kuller, Lh, Price, Jf, Sundström, J, Knuiman, Mw, Feskens, Ej, Verschuren, Wm, Wald, N, Bakker, Sj, Whincup, Ph, Ford, I, Goldbourt, U, Gómez de la Cámara, A, Gallacher, J, Simons, La, Rosengren, A, Sutherland, Se, Björkelund, C, Blazer, Dg, Wassertheil Smoller, S, Onat, A, Marín Ibañez, A, Casiglia, E, Jukema, Jw, Simpson, Lm, Giampaoli, S, Nordestgaard, Bg, Selmer, R, Wennberg, P, Kauhanen, J, Salonen, Jt, Dankner, R, Barrett Connor, E, Kavousi, M, Gudnason, V, Evans, D, Wallace, Rb, Cushman, M, D'Agostino RB, Sr, Umans, Jg, Kiyohara, Y, Nakagawa, H, Sato, S, Gillum, Rf, Folsom, Ar, van der Schouw, Yt, Moons, Kg, Griffin, Sj, Sattar, N, Wareham, Nj, Selvin, E, Thompson, Sg, Danesh J., Collaborators Simpson LM, Coresh, J, Wagenknecht, L, Shaw, Je, Zimmet, Pz, Magliano, D, Wannamethee, Sg, Morris, Rw, Kiechl, S, Santer, P, Bonora, E, Casas, Jp, Ebrahim, S, Ben Shlomo, Y, Yarnell, Jw, Elwood, P, Bachman, Dl, Nietert, Pj, Håheim, Ll, Søgaard, Aj, Tybjaerg Hansen, A, Frikke Schmidt, R, Benn, M, Palmieri, L, Vanuzzo, D, Panico, Salvatore, Bonnet, F, Copin, N, Roussel, R, Gómez Gerique, Ja, Rubio Herrera, Ma, Gutiérrez Fuentes, Ja, Friedlander, Y, Mccallum, J, Simons, J, Lee, Aj, Mclachlan, S, Taylor, Jo, Guralnik, Jm, Phillips, Cl, Evans, Da, Kohout, F, Cohen, H, George, L, Fillenbaum, G, Mcgloin, Jm, Khaw, K., Schöttker, B, Müller, H, Rothenbacher, D, Jansson, J., Hallmans, G, Tuomilehto, J, Donfrancesco, C, Woodward, M, Oizumi, T, Kayama, T, Kato, T, Danker, R, Chetrit, A, Wilhelmsen, L, Eriksson, H, Lappas, G, Bengtsson, C, Lissner, L, Skoog, I, Cremer, P, Arima, H, Ninomiya, T, Hata, J, Nijpels, G, Stehouwer, Cd, Tuomainen, T., Voutilainen, S, Kurl, S, de Boer, Ih, Bertoni, Ag, Veschuren, Wm, Dullaart, Rp, Lambers Heerspink, Hj, Hilege, Hl, Trompet, S, Stott, Dj, Dagenais, Gr, Cantin, B, Dehghan, D, Hofman, A, Franco, Oh, Tunstall Pedoe, H, Lee, E, Best, L, Howard, Bv, Can, G, Ademoğlu, E, Sakurai, M, Nakamura, K, Morikawa, Y, Løchen, M., Mathiesen, Eb, Wilsgaard, T, Byberg, L, Cederholm, T, Olsson, E, Pradhan, Ad, Cook, Nr, Kromhout, D, Walker, M, Watson, S, Burgess, S, Gregson, J, Harshfield, E, Pennells, L, Spackman, S, Warnakula, S, Wood, Am, and Danesh, J.
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- 2014
11. GWAS for executive function and processing speed suggests involvement of the CADM2 gene
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Ibrahim-Verbaas, CA, Bressler, J, Debette, S, Schuur, M, Smith, AV, Bis, JC, Davies, G, Trompet, S, Smith, JA, Wolf, C, Chibnik, LB, Liu, Y, Vitart, V, Kirin, M, Petrovic, K, Polasek, O, Zgaga, L, Fawns-Ritchie, C, Hoffmann, P, Karjalainen, J, Lahti, J, Llewellyn, DJ, Schmidt, CO, Mather, KA, Chouraki, V, Sun, Q, Resnick, SM, Rose, LM, Oldmeadow, C, Stewart, M, Smith, BH, Gudnason, V, Yang, Q, Mirza, SS, Jukema, JW, deJager, PL, Harris, TB, Liewald, DC, Amin, N, Coker, LH, Stegle, O, Lopez, OL, Schmidt, R, Teumer, A, Ford, I, Karbalai, N, Becker, JT, Jonsdottir, MK, Au, R, Fehrmann, Rsn, Herms, S, Nalls, M, Zhao, W, Turner, ST, Yaffe, K, Lohman, K, van Swieten, JC, Kardia, Slr, Knopman, DS, Meeks, WM, Heiss, G, Holliday, EG, Schofield, PW, Tanaka, T, Stott, DJ, Wang, J, Ridker, P, Gow, AJ, Pattie, A, Starr, JM, Hocking, LJ, Armstrong, NJ, McLachlan, S, Shulman, JM, Pilling, LC, Eiriksdottir, G, Scott, RJ, Kochan, NA, Palotie, A, Hsieh, Y-C, Eriksson, JG, Penman, A, Gottesman, RF, Oostra, BA, Yu, L, DeStefano, AL, Beiser, A, Garcia, M, Rotter, JI, Nöthen, MM, Hofman, A, Slagboom, PE, Westendorp, Rgj, Buckley, BM, Wolf, PA, Uitterlinden, AG, Psaty, BM, Grabe, HJ, Bandinelli, S, and Chasman, DI
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Male ,Aging ,European Continental Ancestry Group ,and over ,Neuropsychological Tests ,Medical and Health Sciences ,White People ,Cohort Studies ,Executive Function ,Cognition ,Clinical Research ,Genetics ,80 and over ,2.1 Biological and endogenous factors ,Humans ,Aetiology ,Polymorphism ,gamma-Aminobutyric Acid ,Genetic Association Studies ,Aged ,Psychiatry ,Human Genome ,Psychology and Cognitive Sciences ,Neurosciences ,Genetic Variation ,Genomics ,Single Nucleotide ,Middle Aged ,Biological Sciences ,Introns ,Female ,Generation Scotland ,Cell Adhesion Molecules ,Genome-Wide Association Study - Abstract
To identify common variants contributing to normal variation in two specific domains of cognitive functioning, we conducted a genome-wide association study (GWAS) of executive functioning and information processing speed in non-demented older adults from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) consortium. Neuropsychological testing was available for 5429-32,070 subjects of European ancestry aged 45 years or older, free of dementia and clinical stroke at the time of cognitive testing from 20 cohorts in the discovery phase. We analyzed performance on the Trail Making Test parts A and B, the Letter Digit Substitution Test (LDST), the Digit Symbol Substitution Task (DSST), semantic and phonemic fluency tests, and the Stroop Color and Word Test. Replication was sought in 1311-21860 subjects from 20 independent cohorts. A significant association was observed in the discovery cohorts for the single-nucleotide polymorphism (SNP) rs17518584 (discovery P-value=3.12 × 10(-8)) and in the joint discovery and replication meta-analysis (P-value=3.28 × 10(-9) after adjustment for age, gender and education) in an intron of the gene cell adhesion molecule 2 (CADM2) for performance on the LDST/DSST. Rs17518584 is located about 170 kb upstream of the transcription start site of the major transcript for the CADM2 gene, but is within an intron of a variant transcript that includes an alternative first exon. The variant is associated with expression of CADM2 in the cingulate cortex (P-value=4 × 10(-4)). The protein encoded by CADM2 is involved in glutamate signaling (P-value=7.22 × 10(-15)), gamma-aminobutyric acid (GABA) transport (P-value=1.36 × 10(-11)) and neuron cell-cell adhesion (P-value=1.48 × 10(-13)). Our findings suggest that genetic variation in the CADM2 gene is associated with individual differences in information processing speed.
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- 2016
12. Post-intervention IVUS is not predictive for very late in-stent thrombosis in drug-eluting stents
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Van der Bom Jg, Frits R. Rosendaal, Liem Ss, Jukema Jw, Martin J. Schalij, Sandrin C. Bergheanu, Ayman K.M. Hassan, Jouke Dijkstra, and Van der Hoeven Bl
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Adult ,Male ,medicine.medical_specialty ,Time Factors ,medicine.medical_treatment ,Myocardial Infarction ,Coronary Angiography ,Sudden death ,Post-intervention ,Electrocardiography ,Predictive Value of Tests ,medicine ,Humans ,cardiovascular diseases ,Myocardial infarction ,Stent thrombosis ,Angioplasty, Balloon, Coronary ,Ultrasonography, Interventional ,Aged, 80 and over ,Aspirin ,business.industry ,Coronary Thrombosis ,Stent ,Drug-Eluting Stents ,General Medicine ,Middle Aged ,equipment and supplies ,medicine.disease ,Thrombosis ,Prosthesis Failure ,surgical procedures, operative ,Female ,Radiology ,Cardiology and Cardiovascular Medicine ,Complication ,business ,Follow-Up Studies ,medicine.drug - Abstract
OBJECTIVES Stent thrombosis is a life-threatening complication associated with sudden death and acute myocardial infarction. Histopathologic studies have linked the occurrence of very late stent thrombosis in drug-eluting stents (DES) with delayed endothealisation and stent malapposition. Our aim was to investigate if late stent malapposition in DES could be predicted by immediate postintervention intra-vascular ultrasonography (IVUS). METHODS AND RESULTS From our MISSION! database of 184 consecutive patients with ST-elevation myocardial infarction (STEMI) who had immediate post-intervention and nine-month follow-up IVUS examinations we prospectively identified three patients with very late (> 365 days) and definite (with angiographic evidence) in-stent thrombosis in DES. Patients had completed the twelve-month clopidogrel-aspirin dual treatment period, two of them were under aspirin therapy while the third patient had aspirin temporarily discontinued before planned surgery. When assessed by serial documentary (immediate post-intervention and nine-month) IVUS, all three patients demonstrated stent malapposition at nine months: in two cases the malapposition was acquired (immediate post-intervention IVUS showed a well apposed stent) and one case presented persistent malapposition (the stent was found malapposed both at immediate post-intervention and nine-month follow-up IVUS). CONCLUSIONS Immediate post-intervention IVUS showing no malapposition does not guarantee an uneventful course after DES implantation.
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- 2009
13. Genetic contributions to variation in general cognitive function: a meta-analysis of genome-wide association studies in the CHARGE consortium (N=53949)
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Davies, G, Armstrong, N, Bis, JC, Bressler, J, Chouraki, V, Giddaluru, S, Hofer, E, Ibrahim-Verbaas, CA, Kirin, M, Lahti, J, van der Lee, SJ, Le Hellard, S, Liu, T, Marioni, RE, Oldmeadow, C, Postmus, I, Smith, AV, Smith, JA, Thalamuthu, A, Thomson, R, Vitart, V, Wang, J, Yu, L, Zgaga, L, Zhao, W, Boxall, R, Harris, SE, Hill, WD, Liewald, DC, Luciano, M, Adams, H, Ames, D, Amin, N, Amouyel, P, Assareh, AA, Au, R, Becker, JT, Beiser, A, Berr, C, Bertram, L, Boerwinkle, E, Buckley, BM, Campbell, H, Corley, J, De Jager, PL, Dufouil, C, Eriksson, JG, Espeseth, T, Faul, JD, Ford, I, Generation Scotland, Gottesman, RF, Griswold, ME, Gudnason, V, Harris, TB, Heiss, G, Hofman, A, Holliday, EG, Huffman, J, Kardia, SLR, Kochan, N, Knopman, DS, Kwok, JB, Lambert, J-C, Lee, T, Li, G, Li, S-C, Loitfelder, M, Lopez, OL, Lundervold, AJ, Lundqvist, A, Mather, KA, Mirza, SS, Nyberg, L, Oostra, BA, Palotie, A, Papenberg, G, Pattie, A, Petrovic, K, Polasek, O, Psaty, BM, Redmond, P, Reppermund, S, Rotter, JI, Schmidt, H, Schuur, M, Schofield, PW, Scott, RJ, Steen, VM, Stott, DJ, van Swieten, JC, Taylor, KD, Trollor, J, Trompet, S, Uitterlinden, AG, Weinstein, G, Widen, E, Windham, BG, Jukema, JW, and Wright, AF
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Male ,Aging ,and over ,Neurodegenerative ,Neuropsychological Tests ,Alzheimer's Disease ,Basic Behavioral and Social Science ,Medical and Health Sciences ,Cohort Studies ,Cognition ,Clinical Research ,Behavioral and Social Science ,Genetics ,Acquired Cognitive Impairment ,80 and over ,2.1 Biological and endogenous factors ,Humans ,Genetic Predisposition to Disease ,Aetiology ,Polymorphism ,Aged ,Psychiatry ,Prevention ,Human Genome ,Psychology and Cognitive Sciences ,Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) ,Single Nucleotide ,Middle Aged ,Biological Sciences ,Atherosclerosis ,Brain Disorders ,Phenotype ,Scotland ,Dementia ,Female ,Generation Scotland ,Cognition Disorders ,HMGN1 Protein ,Biotechnology ,Genome-Wide Association Study - Abstract
General cognitive function is substantially heritable across the human life course from adolescence to old age. We investigated the genetic contribution to variation in this important, health- and well-being-related trait in middle-aged and older adults. We conducted a meta-analysis of genome-wide association studies of 31 cohorts (N=53,949) in which the participants had undertaken multiple, diverse cognitive tests. A general cognitive function phenotype was tested for, and created in each cohort by principal component analysis. We report 13 genome-wide significant single-nucleotide polymorphism (SNP) associations in three genomic regions, 6q16.1, 14q12 and 19q13.32 (best SNP and closest gene, respectively: rs10457441, P=3.93 × 10(-9), MIR2113; rs17522122, P=2.55 × 10(-8), AKAP6; rs10119, P=5.67 × 10(-9), APOE/TOMM40). We report one gene-based significant association with the HMGN1 gene located on chromosome 21 (P=1 × 10(-6)). These genes have previously been associated with neuropsychiatric phenotypes. Meta-analysis results are consistent with a polygenic model of inheritance. To estimate SNP-based heritability, the genome-wide complex trait analysis procedure was applied to two large cohorts, the Atherosclerosis Risk in Communities Study (N=6617) and the Health and Retirement Study (N=5976). The proportion of phenotypic variation accounted for by all genotyped common SNPs was 29% (s.e.=5%) and 28% (s.e.=7%), respectively. Using polygenic prediction analysis, ~1.2% of the variance in general cognitive function was predicted in the Generation Scotland cohort (N=5487; P=1.5 × 10(-17)). In hypothesis-driven tests, there was significant association between general cognitive function and four genes previously associated with Alzheimer's disease: TOMM40, APOE, ABCG1 and MEF2C.
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- 2015
14. Thrombin-receptor antagonist vorapaxar in acute coronary syndromes
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Tricoci, P, Huang, Z, Held, C, Moliterno, Dj, Armstrong, Pw, Van de Werf, F, White, Hd, Aylward, Pe, Wallentin, L, Chen, E, Lokhnygina, Y, Pei, J, Leonardi, S, Rorick, Tl, Kilian, Am, Jennings, Lh, Ambrosio, G, Bode, C, Cequier, A, Cornel, Jh, Diaz, R, Erkan, A, Huber, K, Hudson, Mp, Jiang, L, Jukema, Jw, Lewis, Bs, Lincoff, Am, Montalescot, G, Nicolau, Jc, Ogawa, H, Pfisterer, M, Prieto, Jc, Ruzyllo, W, Sinnaeve, Pr, Storey, Rf, Valgimigli, M, Whellan, Dj, Widimsky, P, Strony, J, Harrington, Ra, Mahaffey, Kw, Huo, Y, Lixin, J, Isaza, D, Grande, P, Laine, M, Wong, L, Ofner, P, Yamaguchi, T, Park, Sj, Nordrehaug, Je, Providencia, L, Cheem, Th, Dalby, A, Betriu, A, Chen, Mf, Verheugt, F, Frye, Rl, Hochman, J, Steg, Pg, Bailey, Kr, Easton, Jd, Lincoff, A, Underwood, Fd, Wrestler, J, Larson, D, Vandyne, B, Kilian, A, Harmelin-Kadouri, R, Layton, L, Lipka, L, Petrauskas, S, Qidwai, M, Sorochuck, C, Temple, T, Mason, D, Sydlowski, D, Gallagher, B, Villasin, A, Beernaert, A, Douglas, S, Garrett, J, Wiering, J, Adriaenssens, T, Ganame, J, Hulselmans, M, Katz, Jn, Kayaert, P, La Gerche, A, Onsea, K, Zalewski, J, Johnson, A, O'Briant, J, Smith, M, Akerblom, A, Armaganijan, L, Bertolami, A, Brennan, M, da Ponte Nacif SA, de Campos Gonzaga, C, Dequadros, A, Déry, Jp, Dev, S, Ducrocq, G, Eapen, Zp, Echenique, L, Eggers, K, Garcia, H, Guimaraes, Hp, Hagstrom, E, Hanet, C, James, S, Jonelid, B, Kolls, Bj, Leiria, T, Leite, R, Lombardi, C, Lopes, Rd, Malagutti, P, Mathews, R, Mehta, Rh, Melloni, C, Piccini, Jp, Rodriques Soares, P, Roe, Mt, Shah, Br, Stashenko, G, Szczech, La, Truffa, A, Varenhorst, C, Vranckx, P, Williams, J, Kilaru, R, White, Ja, Binkowitz, B, He, W, Ramos, Ms, Hasbani, E, Farras, Ha, Luz del Valle, L, Zapata, G, Centeno, Ep, Hominal, M, Beloscar, J, Panno, M, Berli, M, Carlevaro, O, Wasserman, T, Lembo, L, Diez, F, Bettinotti, M, Allall, O, Macin, S, Hii, C, Bett, N, Aroney, C, Roberts-Thomson, P, Arstall, M, Horowitz, J, Prasan, A, Farshid, A, Rankin, J, Duffy, S, Sinhal, A, Hendricks, R, Waites, J, Hill, A, French, J, Adams, M, Soward, A, Dick, R, Jepson, N, Nelson, G, Thompson, P, Neunteufl, T, Pachinger, O, Leisch, F, Siostrzonek, P, Roithinger, F, Pieske, B, Weber, H, Eber, B, Zenker, G, Sinnaeve, P, Roosen, J, Vervoort, G, Coussement, P, Striekwold, H, Boland, J, Van Dorpe, A, Dujardin, K, Mertens, D, Vanneste, L, Celen, H, Lesseliers, H, Vrolix, M, Leone, A, De Maeseneire, S, Hellemans, S, Silva, Fa, Franken, M, Moraes JB Jr, Mora, R, Michalaros, Y, Perin, M, Guimaraes, Ae, da Silva DG, Mattos, Ma, Alves AR Jr, Hernandes, Me, Golin, V, da Silva SA, Ardito, W, Dery, Jp, Mukherjee, A, Tanguay, Jf, Kornder, J, Lutchmedial, S, Degrace, M, Klinke, P, Constance, C, Nogareda, G, Wong, G, Macdonald, P, Senaratne, M, Rupka, D, Halperin, F, Ramanathan, K, Natarajan, M, Lai, C, Brossoit, R, Tymchak, W, Rose, B, Dupuis, R, Mansour, S, Bata, I, Zadra, R, Turek, M, Madan, M, Le May, M, Leon, L, Perez, L, Yovaniniz, P, Pedemonte, O, Campos, P, Pincetti, C, Sepulveda, P, Li, W, Zhao, R, Li, Z, Yang, Y, Chen, J, Li, H, Jiang, Y, Li, D, Qu, P, Sun, Y, Zheng, Y, Zhou, C, Zhang, F, Wei, M, Wang, D, Lemus, J, Fernandez, Rl, Jaramillo, C, Ochoa, J, Velez, S, Cano, N, Lutz, J, Botero, R, Jaramillo, M, Saaib, J, Sanchez, G, Hernandez, H, Mendoza, F, Rizcala, A, Urina, M, Polasek, R, Motovska, Z, Zemanek, D, Ostransky, J, Kettner, J, Spinar, J, Groch, L, Ramik, C, Stumar, J, Linhart, A, Pleva, L, Niedobova, E, Macha, J, Vojacek, J, Stipal, R, Galatius, S, Eggert, S, Mickley, H, Egstrup, K, Pedersen, O, Hvilsted, L, Sykulski, R, Skagen, K, Dodt, K, Klarlund, K, Husted, S, Jensen, G, Melchior, T, Sjoel, A, Steffensen, Fh, Airaksinen, Ke, Laukkanen, Ja, Syvanne, Ms, Kotila, Mj, Mikael, K, Naveri, Hk, Hekkala, Am, Mustonen, Jn, Halkosaari, M, Ohlmann, P, Khalife, K, Dibon, O, Hirsch, Jl, Furber, A, Nguyen-Khac, Jo, Delarche, N, Probst, V, Lim, P, Bayet, G, Dauphin, R, Levai, L, Galinier, M, Belhassane, A, Wiedemann, Jy, Fouche, R, Coisne, D, Henry, P, Schiele, F, Boueri, Z, Vaquette, B, Davy, Jm, Cottin, Y, D'Houdain, F, Danchin, N, Cassat, C, Messner, P, Elbaz, M, Coste, P, Zemour, G, Maupas, E, Feldman, L, Soto, Fx, Ferrari, E, Haltern, G, Heuer, H, Genth-Zotz, S, Loges, C, Stellbrink, C, Terres, W, Ferrar, M, Zeymer, U, Brachmann, J, Mudra, H, Vohringer, Hf, vom Dah, J, Kreuzer, J, Hill, S, Kleinertz, K, Kadel, C, Appel, Kf, Nienabe, C, Behrens, S, Frantz, S, Mehrhof, F, Krings, P, Hengstenberg, C, Lueders, S, Hanefel, C, Krulls-Munch, J, Dorse, T, Leschke, M, Nogai, K, Butter, C, Darius, H, Fichtlscherer, Hp, Schmitt, C, Kasisk, Hp, Dorr, M, Fran, N, Jereczek, M, Wiemer, M, Nickenig, G, Boudriot, E, Werner, G, Altila, T, Strasser, R, Baldus, S, Desaga, M, Buerke, M, Land, S, Schunkert, H, Schulze, Ho, Holmer, S, Sohn, Hy, Burkhardt, W, Lauer, B, Schwimmbeck, P, Schoeller, R, Lapp, H, Gross, M, Kindermann, I, Schuster, P, Yu, Cm, Lee, S, Merkely, B, Apro, D, Lupkovics, G, Edes, I, Ungi, I, Piroth, Z, Csapo, K, Dezsi, Ca, Herczeg, B, Sereg, M, Butnaru, A, Lewis, B, Rosenschein, U, Mosseri, M, Turgeman, Y, Pollak, A, Shotan, A, Hammerman, H, Rozenman, Y, Gottlieb, S, Atar, S, Weiss, A, Marmor, A, Iakobishvili, Z, Mascia, F, De Cesare, N, Piovaccari, G, Ceravolo, R, Fiscella, A, Salvioni, A, Silvestri, O, Moretti, L, Severi, S, Carmina, Mg, De Caterina, R, Fattore, L, Terrosu, P, Trimarco, B, Ardissino, D, Uguccioni, L, Auguadro, C, Gregorio, G, De Ferrari, G, Testa, R, Evola, R, De Servi, S, Sganzerla, P, Vassanelli, C, Brunelli, C, Scherillo, M, Tamburino, C, Limido, A, Luzza, F, Percoco, Gf, Sinagra, G, Volpe, M, Crea, F, Fedele, F, Rasetti, G, Cinelli, F, Merlini, P, Sisto, F, Biancoli, S, Fresco, C, Corrada, E, Casolo, G, Santini, M, D'Alessandro, B, Antoniucci, D, Tuccillo, B, Assennato, P, Puccioni, E, Pasquetto, G, Perna, Gp, Morgagni, G, Takizawa, K, Kato, K, Oshima, S, Yagi, M, Asai, T, Kamiya, H, Hirokami, M, Sakota, S, Sueyoshi, A, Shimomura, H, Hashimoto, T, Miyahara, M, Matsumura, T, Nakao, K, Kakuta, T, Nakamura, S, Nishi, Y, Kawajiri, K, Nagai, Y, Takahashi, A, Ikari, Y, Hara, K, Koga, T, Fujii, K, Tobaru, T, Tsunoda, R, Uchiyama, T, Hirayama, H, Fujimoto, K, Sakurai, S, Tanigawa, T, Ohno, M, Yamamoto, E, Ikuta, S, Kato, A, Kikuta, K, Takami, A, Chong, Wp, Ong, Tk, Yusof, A, Maskon, O, Kahar, A, Breedveld, Rw, Bendermacher, Pe, Hamer, Bj, Oude Ophuis AJ, Nierop, Pr, Westendorp, Ic, Beijerbacht, Hp, Herrman, Jp, van 't Hof AW, Troquay, Rp, van der Meer, P, Peters, Rh, van Rossum, P, Liem, A, Pieterse, Mg, van Eck JW, van der Zwaan, C, Pasupati, S, Elliott, J, Tisch, J, Hart, H, Luke, R, Scott, D, Ternouth, I, White, H, Hamer, A, Harding, S, Wilkins, G, O'Meeghan, T, Harrison, N, Nilsen, D, Thalamus, J, Aaberge, L, Brunvand, H, Lutterbey, G, Omland, Tm, Eritsland, J, Wiseth, R, Aase, O, Campos, C, Horna, M, Toce, L, Salazar, M, Przewlocki, T, Ponikowski, P, Kasprzak, J, Kopaczewski, J, Musial, W, Mazurek, W, Kawecka-Jaszcz, K, Pluta, W, Dobrzycki, S, Loboz-Grudzien, K, Lewczuk, J, Karwowski, D, Grajek, S, Dudek, D, Trusz-Gluza, M, Kornacewicz-Jach, Z, Gil, R, Ferreira, J, Gavina, C, Ferreira, R, Martins, D, Garcia-Rinaldi, R, Ufret, R, Vazquez-Tanus, J, Banchs, H, Wong, A, Tan, Hc, Guerra, M, Ebrahim, I, Roux, J, Blomerus, P, Saaiman, A, Corbett, C, Pillay, T, Freeman, V, Horak, A, Zambakides, C, Burgess, L, Yoon, Jh, Ahn, Th, Gwon, Hc, Seong, Iw, Kim, Hs, Jeong, Mh, Kim, Yd, Chae, Sc, Hernandez, Jm, Pique, M, Fernandez Portales, J, Paz, Ma, Lopez Palop, R, Iniguez, A, Diaz Fernandez, J, Alvarez, P, Sanz, E, Heras, M, Sala, J, Goicolea, J, Cruz Fernandez, J, Serra, A, Fernandez Ortiz, A, Calle, G, Barriales, V, Albarran, A, Curos, A, Molano Casimiro FJ, Suarez, Ma, Franco, Sn, Bayon, J, Suarez, J, Belchi, J, Moreu, J, San Martin, M, Melgares Moreno, R, Aguirre Salcedo, J, Gonzalez Juanatey JR, Martinez Romero, P, Galache Osuna JG, Albertsson, P, Diderholm, E, Lycksell, M, Rasmanis, G, Swahn, E, Cherfan, P, Christensen, K, Lundman, P, Larson, Le, Vasko, P, Pripp, Cm, Johansson, A, Moccetti, T, Corti, R, Pieper, M, Mach, F, Eberli, F, Jeger, R, Rickli, H, Vogt, P, Windecker, S, Wu, Cj, Kao, Hl, Charng, Mj, Chang, Kc, Chen, Zc, Tsa, Cd, Shyu, Kg, Lai, Wt, Hsieh, Ic, Hou, Jy, Yeh, Hi, Ueng, Kc, Yin, Wh, Timurkaynak, T, Yigit, Z, Yilmaz, M, Boyaci, A, Sahin, M, Goktekin, O, Bozkurt, E, Ercan, E, Yildirir, A, Muthusamy, R, Keeling, P, Levy, T, Zaman, A, Cohen, A, Gorog, D, Baumbach, A, Oldroyd, K, Kadr, H, Tait, G, Bellenger, N, Davis, G, Shakespeare, C, Senior, R, Bruce, D, Uren, N, Trouton, T, Ahsan, A, Hamed, A, Malik, I, Sarma, J, Millar-Craig, M, Robson, H, Kennon, S, Sprigings, D, Brodie, B, Kang, Gs, Thomas, G, Cheng, Sc, Espinoza, A, Kassas, S, Jafar, Z, Kumar, P, Izzo, M, Wiseman, A, Chandna, H, Felten, W, D'Urso, M, Gudipati, Cr, Coram, R, Gill, S, Bengtson, J, Chang, M, Raisinghani, A, Blankenship, J, Harbor, Wf, Kraft, P, Ashraf, R, Chambers, J, Albirini, A, Malik, A, Ziada, K, Slepian, M, Taussig, A, Vernon, H, Jetty, P, Islam, Ma, Canaday, D, Martin, T, Burchenal, Jj, Gencheff, N, Nygaard, T, Panchal, V, Merritt, R, Abrahams, L, Lambert, C, Reyes, P, Leimbach, W, Chhabra, A, Caputo, R, Imburgia, M, Erickson, B, Kleiman, N, Hunter, J, Dehning, M, Graham, B, Strain, J, White, Jk, Mcgarvey, J Jr, Henderson, D, Treasure, C 2nd, Mirro, M, Pancholy, S, Helmy, T, Westerhausen, D, Dib, N, Penny, W, Kim, H, Degregorio, M, Jay, D, Kmonicek, J, Berlowitz, M, Starling, M, Langevin, E, Nelson, R, Singer, A, Siachos, A, Gibson, G, Parrott, C, Held, J, Puleo, P, Wolford, T, Omar, B, Brilakis, E, Lewis, S, Heller, L, Brener, S, Addo, T, Lieberman, S, Eisenberg, D, Feldman, R, Waksman, R, Waltman, J, Schulman, S, Bounds, C, Voyce, S, Batchelor, W, Dobies, D, Pasnoori, V, Chandrashekhar, Y, Vetrovec, G, Azrin, M, Spriggs, D, Hirsch, C, Smucker, M, Chetcuti, S, Stella, R, Levite, H, Shoukfeh, M, Vidovich, M, Saucedo, J, Fintel, D, Low, R, Gellman, J, Ahsan, C, Unks, Dm, Tolleson, T, Ceccoli, H, Aggarwal, K, Bhaktaram, V, Olson, C, Decaro, M, Kaluski, E, Mehta, V, Puma, J, Singh, V, Fulmer, J, Lewis, D, Khadra, S, Staniloae, C, East, M, Sundram, Ps, Anderson, J, Wasserman, H, Guy, D, Brill, D, Kruse, K, Ebrahimi, R, Nguyen, T, Keating, F, Srivastava, R, Wassmer, P, Todd, J 3rd, Stein, M, Hamzeh, I, Laxson, D, Hodson, R, Puri, S, Vijayaraghavan, K, Gazmuri, R, Chu, A, Vijay, N, Rabinowitz, A, Block, T, Agarwal, H, Martin, J, Zetterlund, P, Fortuin, D, Macdonell, A 3rd, Zouzoulas, S, Chepuri, V, Schmalfuss, C, Karve, M, Aviles, R, Lieberman, E, Amlani, M, Murphy, S, Shapiro, T, Herzog, E, Ariani, K, Bhagwat, R, Hockstad, E, Kai, W, Saririan, M, Roth, R, Weiland, F, Atassi, K, Harjai, K, Muhlestein, J, Marsh, R, Shokooh, S, Nahhas, A, Labroo, A, Mayor, M, Koshy, S, Tariq, M, Rayos, G, Jones, S, Klugherz, B, Dewey, R, Rashid, Hu, Wohns, D, Feiring, A, Bowles, M, Rohrbeck, S, Monroe, Vs, De Gottlieb, A, Gumm, D, Brown, C 3rd, Chang, D, Kalaria, V, Minisi, A, Joumaa, M, Josephson, R, Kleczka, J, Silver, K, Coleman, P, Brachfeld, C, Saltiel, F, Reiner, J, Carell, E, Hanovich, G, Rosenberg, M, Das, G, Blick, D, and Universitat de Barcelona
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Male ,Pyridines ,medicine.medical_treatment ,Kaplan-Meier Estimate ,law.invention ,Lactones ,Randomized controlled trial ,law ,Thrombin receptor antagonist ,clopidogrel ,placebo ,thienopyridine derivative ,vorapaxar ,antithrombocytic agent ,lactone ,proteinase activated receptor 1 ,pyridine derivative ,Coronary Artery Bypass ,Vorapaxar ,Cardiovascular diseases [NCEBP 14] ,Drugs ,General Medicine ,Middle Aged ,Combined Modality Therapy ,Cardiovascular diseases ,Cardiovascular Diseases ,Cardiology ,Platelet aggregation inhibitor ,Drug Therapy, Combination ,Female ,Plaquetes sanguínies ,Intracranial Hemorrhages ,Major bleeding ,Medicaments ,medicine.drug ,medicine.medical_specialty ,Acute coronary syndrome ,Bypass cardiopulmonary ,Hemorrhage ,Pharmacotherapy ,Blood platelets ,Double-Blind Method ,Angioplasty ,Internal medicine ,medicine ,Humans ,Receptor, PAR-1 ,Acute Coronary Syndrome ,Aged ,business.industry ,Malalties cardiovasculars ,medicine.disease ,Surgery ,Bypass cardiopulmonar ,business ,Platelet Aggregation Inhibitors ,Follow-Up Studies - Abstract
Item does not contain fulltext BACKGROUND: Vorapaxar is a new oral protease-activated-receptor 1 (PAR-1) antagonist that inhibits thrombin-induced platelet activation. METHODS: In this multinational, double-blind, randomized trial, we compared vorapaxar with placebo in 12,944 patients who had acute coronary syndromes without ST-segment elevation. The primary end point was a composite of death from cardiovascular causes, myocardial infarction, stroke, recurrent ischemia with rehospitalization, or urgent coronary revascularization. RESULTS: Follow-up in the trial was terminated early after a safety review. After a median follow-up of 502 days (interquartile range, 349 to 667), the primary end point occurred in 1031 of 6473 patients receiving vorapaxar versus 1102 of 6471 patients receiving placebo (Kaplan-Meier 2-year rate, 18.5% vs. 19.9%; hazard ratio, 0.92; 95% confidence interval [CI], 0.85 to 1.01; P=0.07). A composite of death from cardiovascular causes, myocardial infarction, or stroke occurred in 822 patients in the vorapaxar group versus 910 in the placebo group (14.7% and 16.4%, respectively; hazard ratio, 0.89; 95% CI, 0.81 to 0.98; P=0.02). Rates of moderate and severe bleeding were 7.2% in the vorapaxar group and 5.2% in the placebo group (hazard ratio, 1.35; 95% CI, 1.16 to 1.58; P
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- 2012
15. Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure
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Wain, LV, Verwoert, GC, O'Reilly, PF, Shi, G, Johnson, T, Johnson, AD, Bochud, M, Rice, KM, Henneman, P, Smith, AV, Ehret, GB, Amin, N, Larson, MG, Mooser, V, Hadley, D, Dörr, M, Bis, JC, Aspelund, T, Esko, T, Janssens, ACJW, Zhao, JH, Heath, S, Laan, M, Fu, J, Pistis, G, Luan, J, Arora, P, Lucas, G, Pirastu, N, Pichler, I, Jackson, AU, Webster, RJ, Zhang, F, Peden, JF, Schmidt, H, Tanaka, T, Campbell, H, Igl, W, Milaneschi, Y, Hottenga, J-J, Vitart, V, Chasman, DI, Trompet, S, Bragg-Gresham, JL, Alizadeh, BZ, Chambers, JC, Guo, X, Lehtimäki, T, Kühnel, B, Lopez, LM, Polašek, O, Boban, M, Nelson, CP, Morrison, AC, Pihur, V, Ganesh, SK, Hofman, A, Kundu, S, Mattace-Raso, FUS, Rivadeneira, F, Sijbrands, EJG, Uitterlinden, AG, Hwang, S-J, Vasan, RS, Wang, TJ, Bergmann, S, Vollenweider, P, Waeber, G, Laitinen, J, Pouta, A, Zitting, P, McArdle, WL, Kroemer, HK, Völker, U, Völzke, H, Glazer, NL, Taylor, KD, Harris, TB, Alavere, H, Haller, T, Keis, A, Tammesoo, M-L, Aulchenko, Y, Barroso, I, Khaw, K-T, Galan, P, Hercberg, S, Lathrop, M, Eyheramendy, S, Org, E, Sõber, S, Lu, X, Nolte, IM, Penninx, BW, Corre, T, Masciullo, C, Sala, C, Groop, L, Voight, BF, Melander, O, O'Donnell, CJ, Salomaa, V, d'Adamo, AP, Fabretto, A, Faletra, F, Ulivi, S, Del Greco M, F, Facheris, M, Collins, FS, Bergman, RN, Beilby, JP, Hung, J, Musk, AW, Mangino, M, Shin, S-Y, Soranzo, N, Watkins, H, Goel, A, Hamsten, A, Gider, P, Loitfelder, M, Zeginigg, M, Hernandez, D, Najjar, SS, Navarro, P, Wild, SH, Corsi, AM, Singleton, A, de Geus, EJC, Willemsen, G, Parker, AN, Rose, LM, Buckley, B, Stott, D, Orru, M, Uda, M, van der Klauw, MM, Zhang, W, Li, X, Scott, J, Chen, Y-DI, Burke, GL, Kähönen, M, Viikari, J, Döring, A, Meitinger, T, Davies, G, Starr, JM, Emilsson, V, Plump, A, Lindeman, JH, Hoen, PAC', König, IR, Felix, JF, Clarke, R, Hopewell, JC, Ongen, H, Breteler, M, Debette, S, DeStefano, AL, Fornage, M, Mitchell, GF, Smith, NL, Holm, H, Stefansson, K, Thorleifsson, G, Thorsteinsdottir, U, Samani, NJ, Preuss, M, Rudan, I, Hayward, C, Deary, IJ, Wichmann, H-E, Raitakari, OT, Palmas, W, Kooner, JS, Stolk, RP, Jukema, JW, Wright, AF, Boomsma, DI, Bandinelli, S, Gyllensten, UB, Wilson, JF, Ferrucci, L, Schmidt, R, Farrall, M, Spector, TD, Palmer, LJ, Tuomilehto, J, Pfeufer, A, Gasparini, P, Siscovick, D, Altshuler, D, Loos, RJF, Toniolo, D, Snieder, H, Gieger, C, Meneton, P, Wareham, NJ, Oostra, BA, Metspalu, A, Launer, L, Rettig, R, Strachan, DP, Beckmann, JS, Witteman, JCM, Erdmann, J, van Dijk, KW, Boerwinkle, E, Boehnke, M, Ridker, PM, Jarvelin, M-R, Chakravarti, A, Abecasis, GR, Gudnason, V, Newton-Cheh, C, Levy, D, Munroe, PB, Psaty, BM, Caulfield, MJ, Rao, DC, Tobin, MD, Elliott, P, and van Duijn, CM
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- 2011
16. Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease
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Schunkert, H, König, Ir, Kathiresan, S, Reilly, Mp, Assimes, Tl, Holm, H, Preuss, M, Stewart, Af, Barbalic, M, Gieger, C, Absher, D, Aherrahrou, Z, Allayee, H, Altshuler, D, Anand, Ss, Andersen, K, Anderson, Jl, Ardissino, D, Ball, Sg, Balmforth, Aj, Barnes, Ta, Becker, Dm, Becker, Lc, Berger, K, Bis, Jc, Boekholdt, Sm, Boerwinkle, E, Braund, Ps, Brown, Mj, Burnett, Ms, Buysschaert, I, Cardiogenics, Carlquist, Jf, Chen, L, Cichon, S, Codd, V, Davies, Rw, Dedoussis, G, Dehghan, A, Demissie, S, Devaney, Jm, Diemert, P, Do, R, Doering, A, Eifert, S, Mokhtari, Ne, Ellis, Sg, Elosua, R, Engert, Jc, Epstein, Se, de Faire, U, Fischer, M, Folsom, Ar, Freyer, J, Gigante, B, Girelli, Domenico, Gretarsdottir, S, Gudnason, V, Gulcher, Jr, Halperin, E, Hammond, N, Hazen, Sl, Hofman, A, Horne, Bd, Illig, T, Iribarren, C, Jones, Gt, Jukema, Jw, Kaiser, Ma, Kaplan, Lm, Kastelein, Jj, Khaw, Kt, Knowles, Jw, Kolovou, G, Kong, A, Laaksonen, R, Lambrechts, D, Leander, K, Lettre, G, Li, M, Lieb, W, Loley, C, Lotery, Aj, Mannucci, Pm, Maouche, S, Martinelli, Nicola, Mckeown, Pp, Meisinger, C, Meitinger, T, Melander, O, Merlini, Pa, Mooser, V, Morgan, T, Mühleisen, Tw, Muhlestein, Jb, Münzel, T, Musunuru, K, Nahrstaedt, J, Nelson, Cp, Nöthen, Mm, Olivieri, Oliviero, Patel, Rs, Patterson, Cc, Peters, A, Peyvandi, F, Qu, L, Quyyumi, Aa, Rader, Dj, Rallidis, Ls, Rice, C, Rosendaal, Fr, Rubin, D, Salomaa, V, Sampietro, Ml, Sandhu, Ms, Schadt, E, Schäfer, A, Schillert, A, Schreiber, S, Schrezenmeir, J, Schwartz, Sm, Siscovick, Ds, Sivananthan, M, Sivapalaratnam, S, Smith, A, Smith, Tb, Snoep, Jd, Soranzo, N, Spertus, Ja, Stark, K, Stirrups, K, Stoll, M, Tang, Wh, Tennstedt, S, Thorgeirsson, G, Thorleifsson, G, Tomaszewski, M, Uitterlinden, Ag, van Rij AM, Voight, Bf, Wareham, Nj, Wells, Ga, Wichmann, He, Wild, Ps, Willenborg, C, Witteman, Jc, Wright, Bj, Ye, S, Zeller, T, Ziegler, A, Cambien, F, Goodall, Ah, Cupples, La, Quertermous, T, März, W, Hengstenberg, C, Blankenberg, S, Ouwehand, Wh, Hall, As, Deloukas, P, Thompson, Jr, Stefansson, K, Roberts, R, Thorsteinsdottir, U, O'Donnell, Cj, Mcpherson, R, Erdmann, J, the CARDIoGRAM Consortium, Samani, N. J., Epidemiology, Internal Medicine, ACS - Amsterdam Cardiovascular Sciences, Cardiology, and Vascular Medicine
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Adult ,Male ,Multifunction cardiogram ,Locus (genetics) ,Single-nucleotide polymorphism ,Genome-wide association study ,Coronary Artery Disease ,Biology ,Polymorphism, Single Nucleotide ,Genetic determinism ,artery disease ,Article ,Coronary artery disease ,Gene Frequency ,SDG 3 - Good Health and Well-being ,Risk Factors ,Genetics ,medicine ,Humans ,Genetic Predisposition to Disease ,cardiovascular diseases ,Allele ,Genotyping ,Allele frequency ,coronary ,Alleles ,Genetics (clinical) ,Aged ,Genetic association ,business.industry ,Case-control study ,Middle Aged ,medicine.disease ,coronary artery disease ,Large-scale association analysis ,Case-Control Studies ,Female ,Cardiology and Cardiovascular Medicine ,business ,Genome-Wide Association Study - Abstract
1. The CARDIoGRAM Consortium. Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease. Nature Genetics. 2011;43:333–338. ### Study Hypothesis Recently, genome-wide association studies (GWAS) have identified several common variants that are associated with risk of coronary artery disease (CAD) and myocardial infarction (MI). The authors state that the current loci discovered in CAD and MI GWAS explain only a small fraction of the heritability of this complex disease. The authors hypothesized that a larger study would provide more power to discover common variants with modest effect sizes. Therefore, they formed the Coronary ARtery DIsease Genome-wide Replication And Meta-analysis (CARDIoGRAM) consortium, which consisted of data from 14 GWAS of CAD and MI.1 ### How Was the Hypothesis Tested? The authors performed a meta-analysis of 14 GWAS of CAD comprising 22 233 cases and 64 762 control subjects, all of European ancestry. CAD was defined angiographically in a subset (n=7364) and by history in the entire sample. Presence of MI ranged from 48.1% to 100% of each cohort. After the meta-analysis, they genotyped the lead single-nucleotide polymorphisms (SNPs) within the most promising (defined a priori as P 90% power to detect effect sizes observed in the GWAS meta-analysis. Finally, to understand potential mechanisms and intermediate pathways by which novel loci may mediate risk, the authors interrogated 3 genome-wide studies that also assessed gene expression in multiple tissues, using human cell lines, a genome-wide map of allelic expression imbalance, and other human disease traits. ### Principal Findings The analysis of approximately 135 000 individuals more than doubled the number of loci with CAD association, yielding 13 previously unidentified loci and confirming at …
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- 2011
17. Richtlijn 'diagnostiek en behandeling van familiaire hypercholesterolemie' van het college voor zorgverzekeringen
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Walma, Edmond, Visseren, FLJ, Jukema, JW, Kastelein, JJP, Stalenhoef, AFH, Hoes, AW, and General Practice
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- 2006
18. Cholesteryl ester transfer protein expression increases the (V)LDL/HDL ratio and severely aggravates atherosclerosis in APOE*3-Leiden mice
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Westerterp, M, van der Hoogt, CC, de Haan, W, Dallinga-Thie, GM, Jukema, JW, Havekes, LM, Rensen, PCN, and Internal Medicine
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- 2006
19. The cholesterol ester transfer protein (CETP) TaqIB variant, HDL cholesterol levels, cardiovascular risk and the efficacy of pravastatin treatment – an individual patient meta-analisis of 13,677 subjects
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Boekholdt, Sm, Sacks, Fm, Jukema, Jw, Freeman, Dj, Mcmahon, Ad, Cambien, F, Nicaud, V, DE GROOTH GJ, Talmud, Pj, Humphries, Se, Eiriksdottir, G, Gudnason, V, Kauma, H, Kakko, S, Savolainen, Mj, Arca, Marcello, Montali, Anna, Liu, S, Lanz, Hj, Zwinderman, Ah, Kuivenhoven, Ja, and Kastelein, Jjp
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- 2005
20. Association between thrombin-activatable fibrinolysis inhibitor (TAFI) and clinical outcome in patients with unstable agina pectoris
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Brouwers, GJ, Leebeek, Frank, Tanck, MWT, Jukema, JW, Kluft, C, de Maat, Moniek, and Hematology
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- 2003
21. Ìmages in cardiiovascular medicine, malignant right coronary artery anomaly detected by magnetic resonance coronary angiography
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Dirksen, MS (Martijn), Langerak, SE, de Roos, A, Vliegen, HW, Jukema, JW, Bax, JJ, Wielopolski, Piotr, van der Wall, EE, Lamb, HJ, Neurosciences, and Radiology & Nuclear Medicine
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- 2002
22. Raman spectroscopic investigation of the effects of atorvastatin, amlodipine, and both on plaque progression in the aorta of APOE*3 Leiden mice
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Poll, SWE, Delsing, DJM, Jukema, JW, Princen, HMG, Havekes, LM, Puppels, Gerwin, van der Laarse, A, and Surgery
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- 2002
23. Raman spectroscopic evaluation of the effects of diet and lipid-lowering therapy on atherosclerotic plaque development in mice
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Poll, SWE, Römer, TJ, Volger, OL, Delsing, DJM, Bakker Schut, Tom, Princen, HMG, Havekes, LM, Jukema, JW, van der Laarse, A, Puppels, Gerwin, and Surgery
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- 2001
24. Treatment and prevention of coronary heart disease by lowering serum cholesterol levels; from the pioneer work of C.D. de Langen to the third 'Dutch Consensus on Cholestreol'
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Jukema, JW, Simoons, Maarten, and Cardiology
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- 1999
25. 455 G/A polymorphism of the ß-fibrinogen gene is associated with the progression of coronary atherosclerosis in symptomatic men
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de Maat, MPM, Kastelein, JPJ, Jukema, JW, Zwinderman, AH, Jansen, H, Groenemeier, B, Bruschke, AVG, Kluft, C, and Biochemistry
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- 1998
26. Lipoprotein lipase (LPL) activity is decreased in CAD patients and inversely correlated with severity of angina pectoris and silent myocardial ischemia
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Kastelein, Jjp, Jukema, Jw, Boven, Aj, Jansen, H., Zwinderman, Ah, Ton Rabelink, Peters, Rjg, Lie, Ki, Bruschke, Avg, and Hayden, MR
27. Angioplasty with early administration of abciximab in high-risk acute myocardial infarction patients improves clinical outcome
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Beeres, Slma, Oemrawsingh, Pv, Hazem M. Warda, Bechan, R., Atsma, DE, Jukema, Jw, Wall, Ee, and Schalij, Mj
28. No clear role for the-159T/C polymorphism of the CD14 monocyte receptor in progression of atherosclerosis
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Agema, Wrp, Jukema, Jw, Maat, Mpm, Zwinderman, Ah, Kastelein, Jjp, and Ton Rabelink
29. Torcetrapib inhibits cholesterol ester transfer protein, atorvastatin decreases it and both increase HDL in APOE*3-Leiden.CETP transgenic mice
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Hans Princen, Haan, W., Hoogt, Cc, Den Hoogen, Cm, Dallinga-Thie, Gm, Jukema, Jw, Havekes, Lm, and Rensen, Pc
30. Two ecNOS polymorphisms are associated with previous myocardial infarction but not with increased progression of coronary atherosclerosis
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Agema, Wrp, Jukema, Jw, Maat, Mpm, Kraker, J., Zwinderman, Ah, Kastelein, Jjp, and Ton Rabelink
31. Olmesartan and pravastatin additively reduce development of atherosclerosis
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Hoorn, Jw, Jukema, Jw, Havekes, Lm, Kooistra, T., Kleemann, R., and Hans Princen
32. PYRAMID SCORE: perfusion recovery after myocardial infarction diagnostic score
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Hazem M. Warda, Oemrawsingh, Pv, Atsma, DE, Jukema, Jw, Wall, Ee, Laarse, A., and Schalij, Mj
33. No clear role for the-159T/C polymorphism of the CD14 monocyte receptor in progression of atherosclerosis
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Agema, Wrp, Jukema, Jw, Maat, Mpm, Kraker, J., Zwinderman, Ah, Kastelein, Jjp, and Ton Rabelink
34. Not the atherosclerotic burden nor progression of atherosclerosis explain the cardiac event rate in relation to the E/D298 ecNOS polymorphism
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Agema, Wrp, Jukema, Jw, de Maat, MR, Feskens, Ejm, Zwindermans, Ah, Kasteleins, J., Ton Rabelink, and Wall, Ee
35. Calcium-antagonist (amlodipine) and atorvastatin synergy in inhibiting atherosclerosis in apoE*3-leiden mice. The cassia study
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Jukema, Jw, Delsing, Djm, Laarse, A., Boom, H., Offerman, Eh, Havekes, Lm, and Hans Princen
36. Integration of genome-wide association studies with biological knowledge identifies six novel genes related to kidney function
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W. H. Linda Kao, Nicole Probst-Hensch, Florian Ernst, Paul Mitchell, Christa Meisinger, Florian Kronenberg, Sharon L.R. Kardia, Paul M. Ridker, Vilmundur Gudnason, Jeanette S. Andrews, Ming-Huei Chen, Frank B. Hu, Jean-Charles Lambert, Mario Pirastu, Ozren Polasek, Xiaoyi Gao, Sven Bergmann, Catherine Helmer, Wilmar Igl, Jie Jin Wang, Barry I. Freedman, Anke Tönjes, Jacqueline C. M. Witteman, Sheila Ulivi, Conall M. O'Seaghdha, Mika Kähönen, Mariza de Andrade, Daniel I. Chasman, Meredith C. Foster, Rossella Sorice, Mathias Gorski, Eric Boerwinkle, Karlhans Endlich, Maksim Struchalin, Bernhard K. Krämer, Bénédicte Stengel, Caroline Hayward, Giorgio Pistis, Andres Metspalu, Peter Kovacs, Jorma Viikari, Guo Li, Cristian Pattaro, Adrienne Tin, Igor Rudan, Christian Gieger, Mary F. Feitosa, Stephen T. Turner, Gary C. Curhan, Shamika Ketkar, Ian Ford, Peter Vollenweider, Wolfgang Koenig, Madhumathi Rao, Iris M. Heid, Stuart K. Kim, Heather E. Wheeler, Matthias Olden, Hinco J. Gierman, Alex S. F. Doney, Lenore J. Launer, Mladen Boban, Georg Homuth, Paolo Gasparini, Harshal Deshmukh, Henry Völzke, Daniela Ruggiero, Medea Imboden, Elizabeth J. Atkinson, Ben A. Oostra, Stefan Coassin, Ute Nöthlings, Marilyn C. Cornelis, David S. Siscovick, Yongmei Liu, Gian Andri Thun, Gunnar Jacobs, Franco Giulianini, Uwe Völker, Tõnu Esko, Alexander Teumer, Jeffrey R. O'Connell, Brendan M. Buckley, Heyo K. Kroemer, Albert V. Smith, Ulf Gyllensten, Federico Murgia, Man Li, Harry Campbell, Antonietta Robino, Abbas Dehghan, Inga Prokopenko, Shih-Jen Hwang, Sylvia Stracke, Michael Stumvoll, Alan R. Shuldiner, Christian Fuchsberger, Claudia Hundertmark, Luigi Ferrucci, David Ellinghaus, Laura Portas, Caroline S. Fox, Afshin Parsa, Carsten A. Böger, Toshiko Tanaka, Terho Lehtimäki, Ayse Demirkan, James F. Wilson, Elizabeth G. Holliday, Yurii S. Aulchenko, Murielle Bochud, Helen M. Colhoun, Jingzhong Ding, Nicole L. Glazer, Rainer Rettig, Bernhard Paulweber, Margherita Cavalieri, Andre Franke, Ingrid B. Borecki, Olli T. Raitakari, Josef Coresh, Tamara B. Harris, Sarah H. Wild, Reinhold Schmidt, Ching-Ti Liu, Zoltán Kutalik, André G. Uitterlinden, J. Wouter Jukema, Helena Schmidt, Martin Adam, Audrey Y. Chu, Fernando Rivadeneira, Cornelia M. van Duijn, Braxton D. Mitchell, Gudny Eiriksdottir, Tatijana Zemunik, Andrew D. Johnson, Ghazal Zaboli, Reiner Biffar, Thor Aspelund, Cinzia Sala, Peter P. Pramstaller, Veronique Vitart, Michael A. Province, Anna Köttgen, Nicholas D. Hastie, Daniel Taliun, Marina Ciullo, Cosetta Minelli, Kurt Lohman, Matthias Nauck, Thomas Illig, Alan F. Wright, Albert Hofman, Colin N. A. Palmer, Daniela Toniolo, Qiong Yang, Lina Zgaga, Åsa Johansson, Margot Haun, Stella Trompet, Aaron Isaacs, Reedik Mägi, Tiit Nikopensius, Epidemiology, Erasmus School of Social and Behavioural Sciences, Clinical Genetics, Internal Medicine, Chasman, Di, Fuchsberger, C, Pattaro, C, Teumer, A, Böger, Ca, Endlich, K, Olden, M, Chen, Mh, Tin, A, Taliun, D, Li, M, Gao, X, Gorski, M, Yang, Q, Hundertmark, C, Foster, Mc, O'Seaghdha, Cm, Glazer, N, Isaacs, A, Liu, Ct, Smith, Av, O'Connell, Jr, Struchalin, M, Tanaka, T, Li, G, Johnson, Ad, Gierman, Hj, Feitosa, Mf, Hwang, Sj, Atkinson, Ej, Lohman, K, Cornelis, Mc, Johansson, A, Tönjes, A, Dehghan, A, Lambert, Jc, Holliday, Eg, Sorice, R, Kutalik, Z, Lehtimäki, T, Esko, T, Deshmukh, H, Ulivi, S, Chu, Ay, Murgia, F, Trompet, S, Imboden, M, Coassin, S, Pistis, G, Cardiogram, Consortium, Icbp, Consortium, the CARe, Consortium, Wtccc2, Harris, Tb, Launer, Lj, Aspelund, T, Eiriksdottir, G, Mitchell, Bd, Boerwinkle, E, Schmidt, H, Cavalieri, M, Rao, M, Hu, F, Demirkan, A, Oostra, Ba, de Andrade, M, Turner, St, Ding, J, Andrews, J, Freedman, Bi, Giulianini, F, Koenig, W, Illig, T, Meisinger, C, Gieger, C, Zgaga, L, Zemunik, T, Boban, M, Minelli, C, Wheeler, He, Igl, W, Zaboli, G, Wild, Sh, Wright, Af, Campbell, H, Ellinghaus, D, Nöthlings, U, Jacobs, G, Biffar, R, Ernst, F, Homuth, G, Kroemer, Hk, Nauck, M, Stracke, S, Völker, U, Völzke, H, Kovacs, P, Stumvoll, M, Mägi, R, Hofman, A, Uitterlinden, Ag, Rivadeneira, F, Aulchenko, Y, Polasek, O, Hastie, N, Vitart, V, Helmer, C, Wang, Jj, Stengel, B, Ruggiero, D, Bergmann, S, Kähönen, M, Viikari, J, Nikopensius, T, Province, M, Ketkar, S, Colhoun, H, Doney, A, Robino, Antonietta, Krämer, Bk, Portas, L, Ford, I, Buckley, Bm, Adam, M, Thun, Ga, Paulweber, B, Haun, M, Sala, C, Mitchell, P, Ciullo, M, Kim, Sk, Vollenweider, P, Raitakari, O, Metspalu, A, Palmer, C, Gasparini, Paolo, Pirastu, M, Jukema, Jw, Probst Hensch, Nm, Kronenberg, F, Toniolo, D, Gudnason, V, Shuldiner, Ar, Coresh, J, Schmidt, R, Ferrucci, L, Siscovick, D, van Duijn, Cm, Borecki, Ib, Kardia, Sl, Liu, Y, Curhan, Gc, Rudan, I, Gyllensten, U, Wilson, Jf, Franke, A, Pramstaller, Pp, Rettig, R, Prokopenko, I, Witteman, J, Hayward, C, Ridker, Pm, Parsa, A, Bochud, M, Heid, Im, Kao, Wl, Fox, C, and Köttgen, A.
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Candidate gene ,Amino Acid Transport Systems ,Basic/genetics ,Genome-wide association study ,Gene ,Genome ,Inhibin-beta Subunits/genetics ,GWAS ,kidney ,eGFR ,Genetics (clinical) ,Inhibin-beta Subunits ,Glomerular Filtration Rate/genetics ,Genetics ,0303 health sciences ,Genetic Predisposition to Disease/genetics ,Association Studies Articles ,030305 genetics & heredity ,Intracellular Signaling Peptides and Proteins ,General Medicine ,Low Density Lipoprotein Receptor-Related Protein-2/genetics ,Polymorphism, Single Nucleotide/genetics ,LRP2 ,3. Good health ,Low Density Lipoprotein Receptor-Related Protein-2 ,Genome-Wide Association Study/methods ,Single Nucleotide/genetics ,Glomerular Filtration Rate ,Fusion Regulatory Protein 1, Heavy Chain ,Single-nucleotide polymorphism ,Biology ,Polymorphism, Single Nucleotide ,03 medical and health sciences ,Genome-Wide Association Studies ,Humans ,SNP ,Genetic Predisposition to Disease ,ddc:610 ,Membrane Proteins/genetics ,Polymorphism ,Molecular Biology ,030304 developmental biology ,Genetic association ,Fusion Regulatory Protein 1, Heavy Chain/genetics ,Fusion Regulatory Protein 1 ,Genes ,Kidney Function ,Membrane Proteins ,ta3121 ,Amino Acid Transport Systems, Basic ,Amino Acid Transport Systems, Basic/genetics ,Heavy Chain/genetics ,Intracellular Signaling Peptides and Proteins/genetics ,Candidate Disease Gene ,Genome-Wide Association Study - Abstract
In conducting genome-wide association studies (GWAS), analytical approaches leveraging biological information may further understanding of the pathophysiology of clinical traits. To discover novel associations with estimated glomerular filtration rate (eGFR), a measure of kidney function, we developed a strategy for integrating prior biological knowledge into the existing GWAS data for eGFR from the CKDGen Consortium. Our strategy focuses on single nucleotide polymorphism (SNPs) in genes that are connected by functional evidence, determined by literature mining and gene ontology (GO) hierarchies, to genes near previously validated eGFR associations. It then requires association thresholds consistent with multiple testing, and finally evaluates novel candidates by independent replication. Among the samples of European ancestry, we identified a genome-wide significant SNP in FBXL20 (P = 5.6 × 10(-9)) in meta-analysis of all available data, and additional SNPs at the INHBC, LRP2, PLEKHA1, SLC3A2 and SLC7A6 genes meeting multiple-testing corrected significance for replication and overall P-values of 4.5 × 10(-4)-2.2 × 10(-7). Neither the novel PLEKHA1 nor FBXL20 associations, both further supported by association with eGFR among African Americans and with transcript abundance, would have been implicated by eGFR candidate gene approaches. LRP2, encoding the megalin receptor, was identified through connection with the previously known eGFR gene DAB2 and extends understanding of the megalin system in kidney function. These findings highlight integration of existing genome-wide association data with independent biological knowledge to uncover novel candidate eGFR associations, including candidates lacking known connections to kidney-specific pathways. The strategy may also be applicable to other clinical phenotypes, although more testing will be needed to assess its potential for discovery in general.
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- 2012
37. Genetic variation in FTO and mortality
- Author
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Zimmermann, E., Angquist, L.H., Mirza, S.S., Zhao, J.H., Chasman, D.I., Fischer, K., Qi, Q., Smith, A.V., Thinggaard, M., Jarczok, M.N., Nalls, M.A., Trompet, S., Timpson, N.J., Schmidt, B., Jackson, A.U., Lyytikainen, L.P., Verweij, N., Mueller-Nurasyid, M., Vikstrom, M., Marques-Vidal, P., Wong, A., Meidtner, K., Middelberg, R.P., Strawbridge, R.J., Christiansen, L., Kyvik, K.O., Hamsten, A., Jaaskelainen, T., Tjonneland, A., Eriksson, J.G., Whitfield, J.B., Boeing, H., Hardy, R., Vollenweider, P., Leander, K., Peters, A., Harst, P. van der, Kumari, M., Lehtimaki, T., Meirhaeghe, A., Tuomilehto, J., Jockel, K.H., Ben-Shlomo, Y., Sattar, N., Baumeister, S.E., Smith, G.D., Casas, J.P., Houston, D.K., Marz, W., Christensen, K., Gudnason, V., Hu, F.B., Metspalu, A., Ridker, P.M., Wareham, N.J., Loos, R.J.F., Tiemeier, H., Sonestedt, E., Sorensen, T.I.A., The FTO-Mortality Collaborating, Epidemiology, Surgery, Erasmus MC other, Child and Adolescent Psychiatry / Psychology, FTO-Mortality Collaborating Group, Orho-Melander, M., Zillikens, C., Ikram, A., Hofman, A., Luan, J., Khaw, KT., Rose, LM., Läll, K., Mägi, R., Qi, L., Sun, Q., Harris, TB., Launer, LJ., Eiriksdottir, G., Kleber, ME., Delgado, G., Liu, Y., Garcia, M., Teumer, A., Grabe, H., Homuth, G., Jukema, JW., Ford, I., de Craen AJ., Gallacher, J., Yarnell, J., Mahabadi, AA., Nöthen, MM., Erbel, R., Stringham, HM., Boehnke, M., Amouyel, P., Ferrières, J., Arveiler, D., Kähönen, M., Nikus, K., Nieminen, T., Sanchez, A., Kivimaki, M., van Vliet-Ostaptchouk JV., Hampel, R., Thorand, B., De Faire, U., Nyberg, F., Kuh, D., Martin, NG., Montgomery, GW., Heath, AC., Madden, PA., Osmond, C., Pulizzi, N., Roswall, N., Halkjaer, J., Overvad, K., Uusitupa, M., Kinnunen, L., Lindström, J., Saramies, J., Keinänen-Kiukaanniemi, S., Uusitalo, H., Hussi, E., Baldassarre, D., Veglia, F., Humphries, S., Tremoli, E., and Heitmann, B.
- Subjects
obesity ,nutritional and metabolic diseases ,Alpha-Ketoglutarate-Dependent Dioxygenase FTO ,Genetic Variation ,Proteins ,mortality ,Polymorphism, Single Nucleotide ,Article ,Body Mass Index ,meta-analysis ,Observational Studies as Topic ,Humans ,Genetic Predisposition to Disease ,Waist Circumference ,FTO ,Adiposity ,Genome-Wide Association Study - Abstract
Previously, a single nucleotide polymorphism (SNP), rs9939609, in the FTO gene showed a much stronger association with all-cause mortality than expected from its association with body mass index (BMI), body fat mass index (FMI) and waist circumference (WC). This finding implies that the SNP has strong pleiotropic effects on adiposity and adiposity-independent pathological pathways that leads to increased mortality. To investigate this further, we conducted a meta-analysis of similar data from 34 longitudinal studies including 169,551 adult Caucasians among whom 27,100 died during follow-up. Linear regression showed that the minor allele of the FTO SNP was associated with greater BMI (n = 169,551; 0.32 kg m(-2) ; 95% CI 0.28-0.32, P
- Published
- 2015
38. A Meta-Analysis of Thyroid-Related Traits Reveals Novel Loci and Gender-Specific Differences in the Regulation of Thyroid Function
- Author
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McCarthy, M.I., Porcu, E., Medici, M., Pistis, G., Volpato, C.B., Wilson, S.G., Cappola, A.R., Bos, S.D., Deelen, J., den Heijer, M., Freathy, R.M., Lahti, J., Liu, C., Lopez, L.M., Nolte, I.M., O'Connell, J.R., Tanaka, T., Trompet, S., Arnold, A., Bandinelli, S., Beekman, M., Böhringer, S., Brown, S.J., Buckley, B.M., Camaschella, C., de Craen, A.J.M., Davies, G., de Visser, M.C.H., Ford, I., Forsen, T., Frayling, T.M., Fugazzola, L., Gögele, M., Hattersley, A.T., Hermus, A.R., Hofman, A., Houwing-Duistermaat, J.J., Jensen, R.A., Kajantie, E., Kloppenburg, M., Lim, E.M., Masciullo, C., Mariotti, S., Minelli, C., Mitchell, B.D., Nagaraja, R., Netea-Maier, R.T., Palotie, A., Persani, L., Piras, M.G., Psaty, B.M., Räikkönen, K., Richards, J.B., Rivadeneira, F., Sala, C., Sabra, M.M., Sattar, N., Shields, B.M., Soranzo, N., Starr, J.M., Stott, D.J., Sweep, F.C.G.J., Usala, G., van der Klauw, M.M., van Heemst, D., van Mullem, A., H.Vermeulen, S., Visser, W.E., Walsh, J.P., Westendorp, R.G.J., Widen, E., Zhai, G., Cucca, F., Deary, I.J., Eriksson, J.G., Ferrucci, L., Fox, C.S., Jukema, J.W., Kiemeney, L.A., Pramstaller, P.P., Schlessinger, D., Shuldiner, A.R., Slagboom, E.P., Uitterlinden, A.G., Vaidya, B., Visser, T.J., Wolffenbuttel, B.H.R., Meulenbelt, I., Rotter, J.I., Spector, T.D., Hicks, A.A., Toniolo, D., Sanna, S., Peeters, R.P., Naitza, S., Internal Medicine, Clinical Genetics, Public Health, Epidemiology, Internal medicine, ICaR - Circulation and metabolism, Behavioural Sciences, Clinicum, Department of General Practice and Primary Health Care, Children's Hospital, Lastentautien yksikkö, Institute for Molecular Medicine Finland, Haartman Institute (-2014), Department of Medical and Clinical Genetics, Diabetes and Obesity Research Program, Developmental Psychology Research Group, Genomics of Neurological and Neuropsychiatric Disorders, Genomic Discoveries and Clinical Translation, Life Course Epidemiology (LCE), Lifestyle Medicine (LM), Center for Liver, Digestive and Metabolic Diseases (CLDM), Porcu, E, Medici, M, Pistis, G, Volpato, Cb, Wilson, Sg, Cappola, Ar, Bos, Sd, Deelen, J, DEN HEIJER, M, Freathy, Rm, Lahti, J, Liu, C, Lopez, Lm, Nolte, Im, O'Connell, Jr, Tanaka, T, Trompet, S, Arnold, A, Bandinelli, S, Beekman, M, Böhringer, S, Brown, Sj, Buckley, Bm, Camaschella, Clara, DE CRAEN, Aj, Davies, G, DE VISSER, Mc, Ford, I, Forsen, T, Frayling, Tm, Fugazzola, L, Gögele, M, Hattersley, At, Hermus, Ar, Hofman, A, HOUWING DUISTERMAAT, Jj, Jensen, Ra, Kajantie, E, Kloppenburg, M, Lim, Em, Masciullo, C, Mariotti, S, Minelli, C, Mitchell, Bd, Nagaraja, R, NETEA MAIER, Rt, Palotie, A, Persani, L, Piras, Mg, Psaty, Bm, Räikkönen, K, Richards, Jb, Rivadeneira, F, Sala, C, Sabra, Mm, Sattar, N, Shields, Bm, Soranzo, N, Starr, Jm, Stott, Dj, Sweep, Fc, Usala, G, VAN DER KLAUW, Mm, VAN HEEMST, D, VAN MULLEM, A, Vermeulen, Sh, Visser, We, Walsh, Jp, Westendorp, Rg, Widen, E, Zhai, G, Cucca, F, Deary, Ij, Eriksson, Jg, Ferrucci, L, Fox, C, Jukema, Jw, Kiemeney, La, Pramstaller, Pp, Schlessinger, D, Shuldiner, Ar, Slagboom, Ep, Uitterlinden, Ag, Vaidya, B, Visser, Tj, Wolffenbuttel, Bh, Meulenbelt, I, Rotter, Ji, Spector, Td, Hicks, Aa, Toniolo, D, Sanna, S, Peeters, Rp, and Naitza, S.
- Subjects
Male ,Cancer Research ,endocrine system diseases ,Factor binding protein 5 ,Thyroid Gland ,FACTOR BINDING PROTEIN-5 ,Thyrotropin ,Genome-wide association study ,Expression ,Aetiology, screening and detection [ONCOL 5] ,Growth ,Hyperthyroidism ,CLEFT-PALATE ,Serum TSH ,0302 clinical medicine ,Euthyroid ,Genetics (clinical) ,0303 health sciences ,Sex Characteristics ,factor binding protein-S ,Thyroid ,3. Good health ,medicine.anatomical_structure ,Phenotype ,NFIA ,Cleft palate ,GROWTH ,Genome wide Association ,Female ,Thyroid function ,hormones, hormone substitutes, and hormone antagonists ,Research Article ,Signal Transduction ,EXPRESSION ,medicine.medical_specialty ,endocrine system ,lcsh:QH426-470 ,cleft-palate ,515 Psychology ,education ,030209 endocrinology & metabolism ,Biology ,Polymorphism, Single Nucleotide ,Molecular epidemiology [NCEBP 1] ,03 medical and health sciences ,Thyroid-stimulating hormone ,Hypothyroidism ,SERUM TSH ,Internal medicine ,medicine ,Genetics ,Humans ,Hormonal regulation Translational research [IGMD 6] ,GENOME-WIDE ASSOCIATION ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,Health aging / healthy living Cardiovascular diseases [IGMD 5] ,030304 developmental biology ,Molecular epidemiology Aetiology, screening and detection [NCEBP 1] ,Polymorphism, Genetic ,THYROTROPIN ,HORMONE PATHWAY GENES ,Hormonal regulation [IGMD 6] ,R1 ,Thyroxine ,Common variation ,lcsh:Genetics ,Endocrinology ,HYPOTHYROIDISM ,Hormone pathway genes ,genome-wide association ,Hormonal regulation Aetiology, screening and detection [IGMD 6] ,3111 Biomedicine ,COMMON VARIATION ,Hormone ,FOXE1 ,Genome-Wide Association Study ,Developmental Biology - Abstract
Thyroid hormone is essential for normal metabolism and development, and overt abnormalities in thyroid function lead to common endocrine disorders affecting approximately 10% of individuals over their life span. In addition, even mild alterations in thyroid function are associated with weight changes, atrial fibrillation, osteoporosis, and psychiatric disorders. To identify novel variants underlying thyroid function, we performed a large meta-analysis of genome-wide association studies for serum levels of the highly heritable thyroid function markers TSH and FT4, in up to 26,420 and 17,520 euthyroid subjects, respectively. Here we report 26 independent associations, including several novel loci for TSH (PDE10A, VEGFA, IGFBP5, NFIA, SOX9, PRDM11, FGF7, INSR, ABO, MIR1179, NRG1, MBIP, ITPK1, SASH1, GLIS3) and FT4 (LHX3, FOXE1, AADAT, NETO1/FBXO15, LPCAT2/CAPNS2). Notably, only limited overlap was detected between TSH and FT4 associated signals, in spite of the feedback regulation of their circulating levels by the hypothalamic-pituitary-thyroid axis. Five of the reported loci (PDE8B, PDE10A, MAF/LOC440389, NETO1/FBXO15, and LPCAT2/CAPNS2) show strong gender-specific differences, which offer clues for the known sexual dimorphism in thyroid function and related pathologies. Importantly, the TSH-associated loci contribute not only to variation within the normal range, but also to TSH values outside the reference range, suggesting that they may be involved in thyroid dysfunction. Overall, our findings explain, respectively, 5.64% and 2.30% of total TSH and FT4 trait variance, and they improve the current knowledge of the regulation of hypothalamic-pituitary-thyroid axis function and the consequences of genetic variation for hypo- or hyperthyroidism., Author Summary Levels of thyroid hormones are tightly regulated by TSH produced in the pituitary, and even mild alterations in their concentrations are strong indicators of thyroid pathologies, which are very common worldwide. To identify common genetic variants associated with the highly heritable markers of thyroid function, TSH and FT4, we conducted a meta-analysis of genome-wide association studies in 26,420 and 17,520 individuals, respectively, of European ancestry with normal thyroid function. Our analysis identified 26 independent genetic variants regulating these traits, several of which are new, and confirmed previously detected polymorphisms affecting TSH (within the PDE8B gene and near CAPZB, MAF/LOC440389, and NR3C2) and FT4 (within DIO1) levels. Gender-specific differences in the genetic effects of several variants for TSH and FT4 levels were identified at several loci, which offer clues to understand the known sexual dimorphism in thyroid function and pathology. Of particular clinical interest, we show that TSH-associated loci contribute not only to normal variation, but also to TSH values outside reference range, suggesting that they may be involved in thyroid dysfunction. Overall, our findings add to the developing landscape of the regulation of thyroid homeostasis and the consequences of genetic variation for thyroid related diseases.
- Published
- 2013
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