1. Genome-wide association study of intracranial aneurysms identifies 17 risk loci and genetic overlap with clinical risk factors
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Bakker, Mark K., van der Spek, Rick A.A., van Rheenen, Wouter, Morel, Sandrine, Bourcier, Romain, Hostettler, Isabel C., Alg, Varinder S., van Eijk, Kristel R., Koido, Masaru, Akiyama, Masato, Terao, Chikashi, Matsuda, Koichi, Walters, Robin G., Lin, Kuang, Li, Liming, Millwood, Iona Y., Chen, Zhengming, Rouleau, Guy A., Zhou, Sirui, Rannikmäe, Kristiina, Sudlow, Cathie L.M., Houlden, Henry, van den Berg, Leonard H., Dina, Christian, Naggara, Olivier, Gentric, Jean-Christophe, Shotar, Eimad, Eugène, François, Desal, Hubert, Winsvold, Bendik S., Børte, Sigrid, Johnsen, Marianne Bakke, Brumpton, Ben M., Sandvei, Marie Søfteland, Willer, Cristen J., Hveem, Kristian, Zwart, John-Anker, Verschuren, W. M. Monique, Friedrich, Christoph M., Hirsch, Sven, Schilling, Sabine, Dauvillier, Jérôme, Martin, Olivier, Martinsen, Amy E, Aamodt, Anne Hege, Skogholt, Anne Heidi, Sandset, Else Charlotte, Kristoffersen, Espen S, Ellekjaer, Hanne, Heuch, Ingrid, Nielsen, Jonas Bille, Hagen, Knut, Fritsche, Lars, Thomas, Laurent F., Pedersen, Linda, Gabrielsen, Maiken E, Vigeland, Maria Dehli, Holmen, Oddgeir, Zhou, Wei, Chen, Junshi, Chen (PI), Zhengming, Clarke, Robert, Collins, Rory, Guo, Yu, Li (PI), Liming, Liu, Depei, Lv, Jun, Peto, Richard, Walters, Robin, Avery, Daniel, Boxall, Ruth, Bennett, Derrick, Chang, Yumei, Chen, Yiping, Du, Huaidong, Gan, Wei, Gilbert, Simon, Hacker, Alex, Hill, Michael, Holmes, Michael, Iona, Andri, Kartsonaki, Christiana, Kerosi, Rene, Kong, Ling, Lancaster, Garry, Lewington, Sarah, McDonnell, John, Millwood, Iona, Nie, Qunhua, Ryder, Paul, Sansome, Sam, Schmidt-Valle, Dan, Sherliker, Paul, Sohoni, Rajani, Stevens, Becky, Turnbull, Iain, Wang, Lin, Wright, Neil, Yang, Ling, Yang, Xiaoming, Yao, Pang, Bian, Zheng, Han, Xiao, Hou, Can, Pei, Pei, Liu, Chao, Yu, Canqing, Pang, Zengchang, Gao, Ruqin, Li, Shanpeng, Wang, Shaojie, Liu, Yongmei, Du, Ranran, Cheng, Liang, Tian, Xiaocao, Zhang, Hua, Zhai, Yaoming, Ning, Feng, Sun, Xiaohui, Li, Feifei, Lv, Silu, Wang, Junzheng, Hou, Wei, Zou, Mingyuan, Yan, Shichun, Zhou, Xue, Yu, Bo, Li, Yanjie, Xu, Qinai, Kang, Quan, Guo, Ziyan, Wang, Dan, Hu, Ximin, Chen, Jinyan, Fu, Yan, Wang, Xiaohuan, Weng, Min, Guo, Zhendong, Wu, Shukuan, Li, Yilei, Li, Huimei, Wu, Ming, Zhou, Yonglin, Zhou, Jinyi, Tao, Ran, Yang, Jie, Su, Jian, liu, Fang, Zhang, Jun, Hu, Yihe, Lu, Yan, Ma, Liangcai, Tang, Aiyu, Hua, Yujie, Jin, Jianrong, Liu, Jingchao, Tang, Zhenzhu, Chen, Naying, Huang, Ying, Li, Mingqiang, Meng, Jinhuai, Pan, Rong, Jiang, Qilian, Lan, Jian, Liu, Yun, Wei, Liuping, Zhou, Liyuan, Chen, Ningyu, Wang, Ping, Meng, Fanwen, Qin Sisi Wang, Yulu, Wu, Xianping, Zhang, Ningmei, Chen, Xiaofang, Zhou, Weiwei, Luo, Guojin, Li, Jianguo, Zhong, Xunfu, Liu, Jiaqiu, Sun, Qiang, Ge, Pengfei, Ren, Xiaolan, Dong, Caixia, Zhang, Hui, Mao, Enke, Wang, Xiaoping, Wang, Tao, Zhang, Xi, Zhou, Ding Zhang, Zhou, Gang, Feng, Shixian, Chang, Ling, Fan, Lei, Gao, Yulian, He, Tianyou, Sun, Huarong, He, Pan, Hu, Chen, Zhang, Xukui, Wu, Huifang, Yu, Min, Hu, Ruying, Wang, Hao, Gong, Weiwei, Wang, Meng, Xie, Kaixu, Chen, Lingli, Pan, Dongxia, Gu, Qijun, Huang, Yuelong, Chen, Biyun, Yin, Li, Liu, Huilin, Fu, Zhongxi, Xu, Qiaohua, Xu, Xin, Zhang, Hao, Long, Huajun, Zhang, Libo, Nagai, Akiko, Muto, Kaori, Hirata, Makoto, Morisaki, Takayuki, Yamashita, Yasushi, Kamatani, Yoichiro, Kambara, Yoko, Murakami, Yoshinori, Masumoto, Akihide, Nagayama, Satoshi, Miki, Yoshio, Yoshimori, Kozo, Fujioka, Tomoaki, Takata, Ryo, Yamaji, Ken, Takahashi, Kazuhisa, Asai, Satoshi, Takahashi, Yasuo, Minami, Shiro, Yamaguchi, Hiroki, Koretsune, Yukihiro, Nishizawa, Yasuko, Kodama, Ken, Kutsumi, Hiromu, Suzuki, Takao, Sinozaki, Nobuaki, Murayama, Shigeo, Furukawa, Yoichi, Yamanashi, Yuji, Papagiannaki, Chrisanthi, Piotin, Michel, Trystram, Denis, Edjlali-Goujon, Myriam, Boulouis, Grégoire, Rodriguez, Christine, Hassen, Waghi Ben, Saleme, Suzanna, Mounayer, Charbel, Rouchaud, Aymeric, Levrier, Olivier, Aguettaz, Pierre, Combaz, Xavier, Pasco, Anne, l’Allinec, Vincent, Bintner, Marc, Molho, Marc, Pascale, Gauthier, Chivot, Cyril, Costalat, Vincent, Darganzil, Cyril, Bonafé, Alain, Januel, Anne Christine, Michelozzi, Caterina, Cognard, Christophe, Bonneville, Fabrice, Tall, Philippe, Darcourt, Jean, Biondi, Alessandra, Iosif, Cristina, Ferre, Jean Christophe, Gauvrit, Jean Yves, Eugene, François, Raoult, Hélène, Gentric, Jean Christophe, Ognard, Julien, Anxionnat, René, Gory, Benjamin, Bracard, Serge, Derelle, Anne Laure, Tonnelet, Romain, Spelle, Laurent, Ikka, Léon, Ozanne, Augustin, Gallas, Sophie, Caroff, Jildaz, Achour, Nidal Ben, Moret, Jacques, Chabert, Emmanuel, Berge, Jérôme, Marnat, Gaultier, Barreau, Xavier, Gariel, Florent, Clarencon, Frédéric, Aggour, Mohammed, Ricolfi, Frédéric, Chavent, Adrien, Thouant, Pierre, Lebidinsky, Pablo, Lemogne, Brivael, Herbreteau, Denis, Bibi, Richard, Janot, Kevin, Pierot, Laurent, Soize, Sébastien, Labeyrie, Marc Antoine, Vandendries, Christophe, Kazemi, Appoline, Leclerc, Xavier, Pruvo, Jean Pierre, Bricout, Nicolas, Velasco, Stéphane, Boucebci, Samy, Lemmens, Robin, Pandolfo, Massimo, Bodenant, Marie, Louillet, Fabien, Mas, Jean-Louis, Deltour, Sandrine, Leder, Sara, Léger, Anne, Canaple, Sandrine, Godefroy, Olivier, Giroud, Maurice, Jacquin, Agnès, Moulin, Thierry, Vuillier, Fabrice, Tzourio, Christophe, Santos, Michael Dos, Malik, Rainer, Hausser, Ingrid, Thomas-Feles, Constanze, Weber, Ralf, Grond-Ginsbach, Caspar, Hacke, Werner, Giossi, Alessia, Volonghi, Irene, Costa, Paolo, del Zotto, Elisabetta, Morotti, Andrea, Poli, Loris, Muiesan, Maria Lorenza, Salvetti, Massimo, Rosei, Enrico Agabiti, Lanfranconi, Silvia, Baron, Pierluigi, Ferrarese, Carlo, Susani, Emanuela, Giacalone, Giacomo, Paolucci, Stefano, Palmirotta, Raffaele, Guadagni, Fiorella, Paciaroni, Maurizio, Ballabio, Elena, Parati, Eugenio A., Fluri, Felix, Hatz, Florian, Gisler, Dominique, Amort, Margareth, Bevan, Steve, James, Tom, Olsson, Sandra, Holmegaard, Lukas, Altintas, Ayse, Martin, Juan José, Kittner, Steven, Mitchell, Braxton, Stine, Colin, O’Connell, Jeff, Dueker, Nicole, Koudstaal, Peter J., de Lau, Lonneke M.L., Hofman, Albert, Verhaaren, Benjamin F, Uitterlinden, Andre G, Montaner, Joan, Mendioroz, Maite, Yadav, Sunaina, Khan, Muhammad Saleem, Wilder, Michael, van Dijk, Ewoud, Maaijwee, Noortje, Rutten-Jacobs, Loes, Kramer, Jamie, Malik, Shaneela, Brott, Thomas G, Brown, Robert D, Singleton, Andrew, Hardy, John, Rich, Stephen S, Tanislav, Christian, Jungehülsing, Jan, Werring, David, Alg, Varinder, Hostettler, Isabel, Bonner, Stephen, Walsh, Daniel, Bulters, Diederik, Kitchen, Neil, Brown, Martin, Grieve, Joan, Roberts, Gareth, Jones, Timothy, Critchley, Giles, Sharma, Pankaj, Nelson, Richard, Whitfield, Peter, Ross, Stuart, Patel, Hiren, Eldridge, Paul, Saastamoinen, Kari, Patel, Umang, Lawrance, Enas, Vandabona, Subha, Mendelow, David, Teal, Rachel, Warner, Orlando, Kirkpatrick, Peter, Seshadri, Sudha, Kilarski, Laura, Hyacinth, Hyacinth I, Oliveira, Jamary, Marini, Sandro, Nyquist, Paul, Lewis, Cathryn, Norrving, Bo, Smith, Gustav, Rosand, Jonathan, Biffi, Alessandro, Kourkoulis, Christina, Anderson, Chris, Giese, Anne-Katrin, Bang, Oh Young, Chung, Jong-Won, Kim, Gyeong-Moon, Zhuang, Qishuai, Sheu, Wayne, Smalley, June, Howson, Joanna, Granata, Alessandra, Markus, Hugh, Wardlaw, Joanna, Cole, John, Thalamuthu, Anbupalam, Hopewell, Jemma, Worrall, Bradford, Bis, Josh, Tirschwell, David, Reiner, Alex, Dhar, Raj, Lee, Jin-Moo, Mortenson, Janne, Wassertheil-Smoller, Sylvia, Prasad, Kameshwar, Fisher, Mark, Traenka, Christopher, Wang, Xingwu, Wang, Yongjun, Rouanet, Francois, Sibon, Igor, Sarnowski, Chloé, Maillard, Pauline, Aparicio, Hugo Javier, Dupuis, Josee, Yang, Qiong, Luvizutto, Gustavo, Chasman, Daniel, Rexrode, Kathryn, Harriot, Andrea, Phuah, Chia-Ling, Santo, Gustavo, Gerard, Jen, Liu, Guiyou, Aaron, Sanjith, Christudass, Christhunesa S., Salomi, BSB, Sanghera, Dharambir, Boehme, Amelia, Elkind, Mitchell, Gretarsdottir, Solveig, Lange, Leslie, Rost, Natalia, James, Michael, Stewart, Jill, Goldstein, Larry, Waddy, Salina, Vojinovic, Dina, Ikram, Arfan, Thijs, Vincent, Parati, Eugenio, Boncoraglio, Giorgio, Kooperberg, Charles, Abboud, Sherrine, Zand, Ramin, Bijlenga, Philippe, Selim, Magdy, Happola, Olli, Strbian, Daniel, Tomppo, Liisa, Pathak, Abhishek, Pfeiffer, Dorothea, Aires, de Buenos, de Carvalho, Joao Jose Freitas, Ribeiro, Priscila, Torres, Nuria, Barboza, Miguel, Plomaritoglou, Androniki, Bjorkegren, Johan, Chan, Yu-Feng Yvonne, Gudnason, Villi, Jimenez-Conde, Jordi, Soriano, Carolina, Roquer, Jaume, Bentley, Paul, Tournier-Lasserve, Elisabeth, Dufouil, Carole, Debette, Stephanie, Mishra, Aniket, Wee, Lawrence, Siddiqi, Saima, Wu, Jer-Yuarn, Ko, Tai-Ming, Bione, Silvia, Jood, Katarina, Tatlisumak, Turgut, Arauz, Antonio, Korostynski, Michal, Launer, Lenore, Yue, Suo, bersano, anna, Juchniewicz, Karol Józef, Mateusz, Adamski, Pera, Joanna, Wnuk, Marcin, Levi, Christopher, Gusdon, Aaron, Kostulas, Konstantinos, Maxwell, Jessye, Duering, Marco, Jagiella, Jeremiasz, Hata, Jun, Ninomiya, Toshiharu, Nguyen, Vinh, Thorarinsson, Bjorn Logi, Lee, Tsong-Hai, Rakitko, Alexandr, Dichgans, Martin, Lindgren, Arne, Wasselius, Johan, Drake, Mattias, Stenman, Martin, Ilinca, Andreea, Staals, Julie, Sadr-Nabavi, Ariane, Crawford, Katherine, Lena, Umme, Mateen, Farrah, Ay, Hakan, Wu, Ona, Schirmer, Markus, Romero, Javier, Cramer, Steve, Golland, Polina, Mueller, Bertram, Brown, Robert, Meschia, James, Ross, Owen A., Pare, Guillaume, Chong, Mike, mansour, Ossama yassin, Karaszewski, Bartosz, Enzinger, Christian, Schmidt, Reinhold, Seiler, Stephan, Pichler, Alexander, Ovbiagele, Bruce, Yamada, Yoshiji, Rundek, Tatjana, Blanton, Susan, P, John, Chern, Joseph, O'Donnell, Chris, Corriveau, Roderick, Bhattacharya, Pallab, Gwinn, Katrina, CHANDRA, BHARATENDU, Chen, Christopher, Kalaria, Raj, Koenig, Jim, Singh, Om Prakash, Olugbodi, Akintomi, Giralt, Eva, Saleheen, Danish, de Leeuw, Frank-Erik, Klijn, Karin, Olesen, Jes, Kubo, Michiaki, Spence, David, Pedersen, Annie, Olsson, Maja, Martín, Juan José, Braga, Gabriel, Xu, Huichun, Assimes, Tim, Raskurazhev, Anton, Lee, Wei Ling, Burri, Philippe, Frid, Petrea, GmbH, Heilbronn, Deng, Zhen, Habibi-koolaee, Mahdi, Vijayan, Murali, Leung, Thomas, Wong, Lawrence, Mok, Vincent, Choy, Richard, Jern, Christina, Lebedeva, Elena, Farrall, Martin, Jiayuan, Xu, Loo, Keat Wei, Rinkel, Gabriel, Magnus, Rudolf, Goncalves, Anderson, Franca, Paulo, Cendes, Iscia, Carrera, Caty, Fernandez-Cadenas, Israel, Kim, Helen, Rolfs, Arndt, Owolabi, Mayowa, Bakker, Mark, Ruigrok, Ynte, Hauer, Allard, Pulit, Sara L., Algra, Ale, van der Laan, Sander W., Macleod, Mary, Howard, George, Tiwari, Hemant, Irvin, Ryan, Albright, Karen C., Perry, Rodney, Kidwell, Chelsea, Pavlovic, Aleksandra, Sargurupremraj, Murali, Schilling, Sabrina, Pezzini, Alessandro, Abd-Allah, Foad, DeCarli, Charles, Liebeskind, David, Traylor, Matthew, Tan, Rhea, Danesh, John, Larsson, Susanna C., Rutten, Loes, Donatti, Amanda, Avelar, Wagner, Broderick, Joseph, Woo, Daniel, Kissela, Brett, Ibenez, Laura Garcia, Salman, Rustam, Sudlow, Cathie, McDonough, Caitrin Wheeler, Silliman, Scott, Magvanjav, Oyunbileg, van Agtmael, Tom, Walters, Matthew, Lorentzen, Erik, Stanne, Tara, Olsson, Martina, Nakagawa, Kazuma, Akinyemi, Rufus, Cotlatciuc, Ioana, O'Connell, Jeff, Sparks, Mary, Sorkin, John, Dave, Tushar, Naylor, Jill, Brown, Devin, Du, Rose, Kulik, Tobias B., Attia, John, Faber, James E, Rothwell, Peter, Márquez, Elsa Valdés, Mancuso, Michelangelo, Souza, Doralina Brum, de Silva, Ranil, Vibo, Riina, Korv, Janika, Maguire, Jane, Fornage, Myriam, Illoh, Kachikwu, Milewicz, Dianna, Majersik, Jennifer, DeHavenon, Adam, Kalani, Yashar, Alexander, Matthew, Cushman, Mary, Sale, Michele, Owens, Debra, Keene, Keith, Rich, Stephe, Psaty, Bruce, Longstreth, Will, Atadzhanov, Masharip, Wolfe, Stacey Quintero, Langefeld, Carl, Bushnell, Cheryl, Cruchaga, Carlos, Konrad, Jan, Liu, Junfeng, Sheth, Kevin, Falcone, Guido, Donahue J, Kathleen, Jones, Gregory T., Bown, Matthew J., Ko, Nerissa U., Coleman, Jonathan R.I., Breen, Gerome, Zaroff, Jonathan G., Klijn, Catharina J.M., Sargurupremraj, Muralidharan, Amouyel, Philippe, Debette, Stéphanie, Rinkel, Gabriel J.E., Worrall, Bradford B., Slowik, Agnieszka, Gaál-Paavola, Emilia I., Niemelä, Mika, Jääskeläinen, Juha E., von Und Zu Fraunberg, Mikael, Lindgren, Antti, Broderick, Joseph P., Werring, David J., Redon, Richard, Veldink, Jan H., Ruigrok, Ynte M., Stroke, HUNT All-In, Group, China Kadoorie Biobank Collaborative, Consortium, BioBank Japan Project, Group, ICAN Study, Group, CADISP, investigators, Genetics and Observational Subarachnoid Haemorrhage (GOSH) Study, (ISGC), International Stroke Genetics Consortium, Morel, Sandrine, and Bijlenga, Philippe Alexandre Pierre
- Subjects
genetics [Blood Pressure] ,Medizin ,Genome-wide association study ,Blood Pressure ,Disease ,ddc:616.07 ,Bioinformatics ,616: Innere Medizin und Krankheiten ,0302 clinical medicine ,Risk Factors ,physiopathology [Hypertension] ,genetics [Genetic Predisposition to Disease] ,Genetic risk factor ,Stroke ,0303 health sciences ,Smoking ,genetics [Smoking] ,genetics [Intracranial Aneurysm] ,Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3] ,Cerebrovascular disorder ,3. Good health ,genetics [European Continental Ancestry Group] ,Hypertension ,genetics [Polymorphism, Single Nucleotide] ,Subarachnoid hemorrhage ,pathology [Intracranial Aneurysm] ,genetics [White People] ,Biology ,Genetic correlation ,pathology [Endothelial Cells] ,Polymorphism, Single Nucleotide ,Article ,White People ,03 medical and health sciences ,Aneurysm ,Asian People ,ddc:570 ,Genetics ,medicine ,Humans ,Genetic Predisposition to Disease ,cardiovascular diseases ,030304 developmental biology ,genetics [Subarachnoid Hemorrhage] ,genetics [Asian Continental Ancestry Group] ,572: Biochemie ,genetics [Asian People] ,pathology [Subarachnoid Hemorrhage] ,adverse effects [Smoking] ,Endothelial Cells ,Subarachnoid Hemorrhage ,medicine.disease ,Intracranial aneurysm ,Genetic architecture ,ddc:616.8 ,Case-Control Studies ,genetics [Hypertension] ,030217 neurology & neurosurgery ,Genome-Wide Association Study - Abstract
An author correction to this article published in December 2020 is available at https://doi.org/10.1038/s41588-020-00760-4. Rupture of an intracranial aneurysm leads to subarachnoid hemorrhage, a severe type of stroke. To discover new risk loci and the genetic architecture of intracranial aneurysms, we performed a cross-ancestry, genome-wide association study in 10,754 cases and 306,882 controls of European and East Asian ancestry. We discovered 17 risk loci, 11 of which are new. We reveal a polygenic architecture and explain over half of the disease heritability. We show a high genetic correlation between ruptured and unruptured intracranial aneurysms. We also find a suggestive role for endothelial cells by using gene mapping and heritability enrichment. Drug-target enrichment shows pleiotropy between intracranial aneurysms and antiepileptic and sex hormone drugs, providing insights into intracranial aneurysm pathophysiology. Finally, genetic risks for smoking and high blood pressure, the two main clinical risk factors, play important roles in intracranial aneurysm risk, and drive most of the genetic correlation between intracranial aneurysms and other cerebrovascular traits.
- Published
- 2021