Search

Your search keyword '"Berrandou, Takiy"' showing total 40 results
Start Over Author "Berrandou, Takiy"
40 results on '"Berrandou, Takiy"'

1. Genome-wide association meta-analysis of spontaneous coronary artery dissection identifies risk variants and genes related to artery integrity and tissue-mediated coagulation.

Author

Adlam, David, Berrandou, Takiy-Eddine, Georges, Adrien, Nelson, Christopher, Giannoulatou, Eleni, Henry, Joséphine, Ma, Lijiang, Blencowe, Montgomery, Turley, Tamiel, Yang, Min-Lee, Chopade, Sandesh, Finan, Chris, Braund, Peter, Sadeg-Sayoud, Ines, Iismaa, Siiri, Kosel, Matthew, Zhou, Xiang, Hamby, Stephen, Cheng, Jenny, Liu, Lu, Tarr, Ingrid, Muller, David, dEscamard, Valentina, King, Annette, Brunham, Liam, Baranowska-Clarke, Ania, Debette, Stéphanie, Amouyel, Philippe, Olin, Jeffrey, Patil, Snehal, Hesselson, Stephanie, Junday, Keerat, Kanoni, Stavroula, Aragam, Krishna, Butterworth, Adam, Tweet, Marysia, Gulati, Rajiv, Combaret, Nicolas, Kadian-Dodov, Daniella, Kalman, Jonathan, Fatkin, Diane, Hingorani, Aroon, Saw, Jacqueline, Webb, Tom, Hayes, Sharonne, Yang, Xia, Ganesh, Santhi, Olson, Timothy, Kovacic, Jason, Graham, Robert, Samani, Nilesh, and Bouatia-Naji, Nabila

Subjects
Humans, Female, Genome-Wide Association Study, Vascular Diseases, Coronary Artery Disease, Myocardial Infarction
Abstract

Spontaneous coronary artery dissection (SCAD) is an understudied cause of myocardial infarction primarily affecting women. It is not known to what extent SCAD is genetically distinct from other cardiovascular diseases, including atherosclerotic coronary artery disease (CAD). Here we present a genome-wide association meta-analysis (1,917 cases and 9,292 controls) identifying 16 risk loci for SCAD. Integrative functional annotations prioritized genes that are likely to be regulated in vascular smooth muscle cells and artery fibroblasts and implicated in extracellular matrix biology. One locus containing the tissue factor gene F3, which is involved in blood coagulation cascade initiation, appears to be specific for SCAD risk. Several associated variants have diametrically opposite associations with CAD, suggesting that shared biological processes contribute to both diseases, but through different mechanisms. We also infer a causal role for high blood pressure in SCAD. Our findings provide novel pathophysiological insights involving arterial integrity and tissue-mediated coagulation in SCAD and set the stage for future specific therapeutics and preventions.

Published
2023

2. Abstract 4143772: Genome wide association study meta-analysis of 19,487 individuals with mitral valve prolapse identifies 52 novel genomic regions and highlights pro-fibrosis genes

Author

Small, Aeron, Berrandou, Takiy-Eddine, Georges, Adrien, Morningstar, Jordan, Huff, Matthew, Yang, Ta-Yu, Lee, Jiwoo, Abner, Erik, Bundgaard, Henning, Wells, Quinn, Wilson, Peter, Cho, Kelly, Rader, Daniel, Ganna, Andrea, Helgadottir, Anna, Holm, Hilma, Stefansson, Kari, Gudbjartsson, Daniel, Vy, Ha My, Rosenberg, Michael, Milan, David, Borger, Michael, Dieterlen, Maja-Theresa, Kontorovich, Amy, Engert, Jamie, Thanassoulis, George, Farber-Eger, Eric, Gignoux, Christopher, Ellinor, Patrick, Peloso, Gina, Norris, Russell, Yu, Mengyao, Bouatia-Naji, Nabila, and Natarajan, Pradeep

Published
2024
Full Text
View/download PDF

4. Assessment of interactions between 205 breast cancer susceptibility loci and 13 established risk factors in relation to breast cancer risk, in the Breast Cancer Association Consortium

Author

Kapoor, Pooja Middha, Lindström, Sara, Behrens, Sabine, Wang, Xiaoliang, Michailidou, Kyriaki, Bolla, Manjeet K, Wang, Qin, Dennis, Joe, Dunning, Alison M, Pharoah, Paul DP, Schmidt, Marjanka K, Kraft, Peter, García-Closas, Montserrat, Easton, Douglas F, Milne, Roger L, Chang-Claude, Jenny, Ahearn, Thomas, Andrulis, Irene L, Anton-Culver, Hoda, Arndt, Volker, Aronson, Kristan J, Auer, Paul L, Augustinsson, Annelie, Freeman, Laura E Beane, Beckmann, Matthias W, Benitez, Javier, Bernstein, Leslie, Berrandou, Takiy, Bojesen, Stig E, Brauch, Hiltrud, Brenner, Hermann, Brock, Ian W, Broeks, Annegien, Brooks-Wilson, Angela, Butterbach, Katja, Cai, Qiuyin, Campa, Daniele, Canzian, Federico, Carter, Brian D, Castelao, Jose E, Chanock, Stephen J, Chenevix-Trench, Georgia, Cheng, Ting-Yuan David, Clarke, Christine L, Cordina-Duverger, Emilie, Couch, Fergus J, Cox, Angela, Cross, Simon S, Czene, Kamila, Dai, James Y, Dite, Gillian S, Earp, H Shelton, Eliassen, A Heather, Eriksson, Mikael, Evans, D Gareth, Fasching, Peter A, Figueroa, Jonine, Flyger, Henrik, Fritschi, Lin, Gabrielson, Marike, Gago-Dominguez, Manuela, Gapstur, Susan M, Gaudet, Mia M, Giles, Graham G, González-Neira, Anna, Grundy, Anne, Guénel, Pascal, Haeberle, Lothar, Haiman, Christopher A, Håkansson, Niclas, Hall, Per, Hamann, Ute, Hankinson, Susan E, Harkness, Elaine F, Harstad, Tricia, He, Wei, Heyworth, Jane, Hoover, Robert N, Hopper, John L, Humphreys, Keith, Hunter, David J, Marrón, Pablo Isidro, John, Esther M, Jones, Michael E, Jung, Audrey, Kaaks, Rudolf, Keeman, Renske, Kitahara, Cari M, Ko, Yon-Dschun, Koutros, Stella, Krüger, Ute, Lambrechts, Diether, Le Marchand, Loic, Lee, Eunjung, Lejbkowicz, Flavio, Linet, Martha, Lissowska, Jolanta, Llaneza, Ana, Lo, Wing-Yee, and Makalic, Enes

Subjects
Genetics, Estrogen, Clinical Research, Cancer, Breast Cancer, Prevention, 2.1 Biological and endogenous factors, Aetiology, Alleles, Breast Neoplasms, Case-Control Studies, Europe, Factor XIII, Female, Gene-Environment Interaction, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Polymorphism, Single Nucleotide, Receptors, Estrogen, Risk Factors, White People, Breast Cancer Association Consortium, Europeans, Gene-environment interaction, breast cancer, epidemiology, risk factors, single nucleotide polymorphism, Statistics, Public Health and Health Services, Epidemiology
Abstract

BackgroundPrevious gene-environment interaction studies of breast cancer risk have provided sparse evidence of interactions. Using the largest available dataset to date, we performed a comprehensive assessment of potential effect modification of 205 common susceptibility variants by 13 established breast cancer risk factors, including replication of previously reported interactions.MethodsAnalyses were performed using 28 176 cases and 32 209 controls genotyped with iCOGS array and 44 109 cases and 48 145 controls genotyped using OncoArray from the Breast Cancer Association Consortium (BCAC). Gene-environment interactions were assessed using unconditional logistic regression and likelihood ratio tests for breast cancer risk overall and by estrogen-receptor (ER) status. Bayesian false discovery probability was used to assess the noteworthiness of the meta-analysed array-specific interactions.ResultsNoteworthy evidence of interaction at ≤1% prior probability was observed for three single nucleotide polymorphism (SNP)-risk factor pairs. SNP rs4442975 was associated with a greater reduction of risk of ER-positive breast cancer [odds ratio (OR)int = 0.85 (0.78-0.93), Pint = 2.8 x 10-4] and overall breast cancer [ORint = 0.85 (0.78-0.92), Pint = 7.4 x 10-5) in current users of estrogen-progesterone therapy compared with non-users. This finding was supported by replication using OncoArray data of the previously reported interaction between rs13387042 (r2 = 0.93 with rs4442975) and current estrogen-progesterone therapy for overall disease (Pint = 0.004). The two other interactions suggested stronger associations between SNP rs6596100 and ER-negative breast cancer with increasing parity and younger age at first birth.ConclusionsOverall, our study does not suggest strong effect modification of common breast cancer susceptibility variants by established risk factors.

Published
2020

6. Author Correction: Genetic investigation of fibromuscular dysplasia identifies risk loci and shared genetics with common cardiovascular diseases

Author

Georges, Adrien, Yang, Min-Lee, Berrandou, Takiy-Eddine, Bakker, Mark K., Dikilitas, Ozan, Kiando, Soto Romuald, Ma, Lijiang, Satterfield, Benjamin A., Sengupta, Sebanti, Yu, Mengyao, Deleuze, Jean-François, Dupré, Delia, Hunker, Kristina L., Kyryachenko, Sergiy, Liu, Lu, Sayoud-Sadeg, Ines, Amar, Laurence, Brummett, Chad M., Coleman, Dawn M., d’Escamard, Valentina, de Leeuw, Peter, Fendrikova-Mahlay, Natalia, Kadian-Dodov, Daniella, Li, Jun Z., Lorthioir, Aurélien, Pappaccogli, Marco, Prejbisz, Aleksander, Smigielski, Witold, Stanley, James C., Zawistowski, Matthew, Zhou, Xiang, Zöllner, Sebastian, Amouyel, Philippe, De Buyzere, Marc L., Debette, Stéphanie, Dobrowolski, Piotr, Drygas, Wojciech, Gornik, Heather L., Olin, Jeffrey W., Piwonski, Jerzy, Rietzschel, Ernst R., Ruigrok, Ynte M., Vikkula, Miikka, Warchol Celinska, Ewa, Januszewicz, Andrzej, Kullo, Iftikhar J., Azizi, Michel, Jeunemaitre, Xavier, Persu, Alexandre, Kovacic, Jason C., Ganesh, Santhi K., and Bouatia-Naji, Nabila

Published
2022
Full Text
View/download PDF

7. Genetic Risk Score for Intracranial Aneurysms: Prediction of Subarachnoid Hemorrhage and Role in Clinical Heterogeneity

Author

Bakker, Mark K., Kanning, Jos P., Abraham, Gad, Martinsen, Amy E., Winsvold, Bendik S., Zwart, John-Anker, Bourcier, Romain, Sawada, Tomonobu, Koido, Masaru, Kamatani, Yoichiro, Morel, Sandrine, Amouyel, Philippe, Debette, Stéphanie, Bijlenga, Philippe, Berrandou, Takiy, Ganesh, Santhi K., Bouatia-Naji, Nabila, Jones, Gregory, Bown, Matthew, Rinkel, Gabriel J.E., Veldink, Jan H., Ruigrok, Ynte M., Hege Aamodt, Anne, Heidi Skogholt, Anne, Brumpton, Ben M, Willer, Cristen J, Sandset, Else C, Kristoffersen, Espen S, Ellekjær, Hanne, Heuch, Ingrid, Nielsen, Jonas B, Hagen, Knut, Hveem, Kristian, Fritsche, Lars G, Thomas, Laurent F, Pedersen, Linda M, Gabrielsen, Maiken E, Holmen, Oddgeir L, Børte, Sigrid, Zhou, Wei, Abboud, Shérine, Pandolfo, Massimo, Thijs, Vincent, Leys, Didier, Bodenant, Marie, Louillet, Fabien, Touzé, Emmanuel, Mas, Jean-Louis, Samson, Yves, Leder, Sara, Léger, Anne, Deltour, Sandrine, Crozier, Sophie, Méresse, Isabelle, Canaple, Sandrine, Godefroy, Olivier, Giroud, Maurice, Béjot, Yannick, Decavel, Pierre, Medeiros, Elizabeth, Montiel, Paola, Moulin, Thierry, Vuillier, Fabrice, Dallongeville, Jean, Metso, Antti J, Metso, Tiina, Tatlisumak, Turgut, Grond-Ginsbach, Caspar, Lichy, Christoph, Kloss, Manja, Werner, Inge, Arnold, Marie-Luise, Dos Santos, Michael, Grau, Armin, Dichgans, Martin, Thomas-Feles, Constanze, Weber, Ralf, Brandt, Tobias, Pezzini, Alessandro, De Giuli, Valeria, Caria, Filomena, Poli, Loris, Padovani, Alessandro, Bersano, Anna, Lanfranconi, Silvia, Beretta, Simone, Ferrarese, Carlo, Giacolone, Giacomo, Paolucci, Stefano, Lyrer, Philippe, Engelter, Stefan, Fluri, Felix, Hatz, Florian, Gisler, Dominique, Bonati, Leo, Gensicke, Henrik, Amort, Margareth, Markus, Hugh, Majersik, Jennifer, Worrall, Bradford, Southerland, Andrew, Cole, John, Kittner, Steven, Evangelou, Evangelos, Warren, Helen R, Gao, He, Ntritsos, Georgios, Dimou, Niki, Esko, Tonu, Mägi, Reedik, Milani, Lili, Almgren, Peter, Boutin, Thibaud, Ding, Jun, Giulianini, Franco, Holliday, Elizabeth G, Jackson, Anne U, Li-Gao, Ruifang, Lin, Wei-Yu, Luan, Jian’an, Mangino, Massimo, Oldmeadow, Christopher, Peter Prins, Bram, Qian, Yong, Sargurupremraj, Muralidharan, Shah, Nabi, Surendran, Praveen, Thériault, Sébastien, Verweij, Niek, Willems, Sara M, Zhao, Jing-Hua, Connell, John, de Mutsert, Renée, Doney, Alex SF, Farrall, Martin, Menni, Cristina, Morris, Andrew D, Noordam, Raymond, Paré, Guillaume, Poulter, Neil R, Shields, Denis C, Stanton, Alice, Thom, Simon, Abecasis, Gonçalo, Amin, Najaf, Arking, Dan E, Ayers, Kristin L, Barbieri, Caterina M, Batini, Chiara, Bis, Joshua C, Blake, Tineka, Bochud, Murielle, Boehnke, Michael, Boerwinkle, Eric, Boomsma, Dorret I, Bottinger, Erwin P, Braund, Peter S, Brumat, Marco, Campbell, Archie, Campbell, Harry, Chakravarti, Aravinda, Chambers, John C, Chauhan, Ganesh, Ciullo, Marina, Cocca, Massimiliano, Collins, Francis, Cordell, Heather J, Davies, Gail, de Borst, Martin H, de Geus, Eco J, Deary, Ian J, Deelen, Joris, Del Greco M, Fabiola, Yusuf Demirkale, Cumhur, Dörr, Marcus, Ehret, Georg B, Elosua, Roberto, Enroth, Stefan, Mesut Erzurumluoglu, A, Ferreira, Teresa, Frånberg, Mattias, Franco, Oscar H, Gandin, Ilaria, Gasparini, Paolo, Giedraitis, Vilmantas, Gieger, Christian, Girotto, Giorgia, Goel, Anuj, Gow, Alan J, Gudnason, Vilmundur, Guo, Xiuqing, Gyllensten, Ulf, Hamsten, Anders, Harris, Tamara B, Harris, Sarah E, Hartman, Catharina A, Havulinna, Aki S, Hicks, Andrew A, Hofer, Edith, Hofman, Albert, Hottenga, Jouke-Jan, Huffman, Jennifer E, Hwang, Shih-Jen, Ingelsson, Erik, James, Alan, Jansen, Rick, Jarvelin, Marjo-Riitta, Joehanes, Roby, Johansson, Åsa, Johnson, Andrew D, Joshi, Peter K, Jousilahti, Pekka, Wouter Jukema, J, Jula, Antti, Kähönen, Mika, Kathiresan, Sekar, Keavney, Bernard D, Khaw, Kay-Tee, Knekt, Paul, Knight, Joanne, Kolcic, Ivana, Kooner, Jaspal S, Koskinen, Seppo, Kristiansson, Kati, Kutalik, Zoltan, Laan, Maris, Larson, Marty, Launer, Lenore J, Lehne, Benjamin, Lehtimäki, Terho, Liewald, David CM, Lin, Li, Lind, Lars, Lindgren, Cecilia M, Liu, YongMei, Loos, Ruth JF, Lopez, Lorna M, Lu, Yingchang, Lyytikäinen, Leo-Pekka, Mahajan, Anubha, Mamasoula, Chrysovalanto, Marrugat, Jaume, Marten, Jonathan, Milaneschi, Yuri, Morgan, Anna, Morris, Andrew P, Morrison, Alanna C, Munson, Peter J, Nalls, Mike A, Nandakumar, Priyanka, Nelson, Christopher P, Niiranen, Teemu, Nolte, Ilja M, Nutile, Teresa, Oldehinkel, Albertine J, Oostra, Ben A, O’Reilly, Paul F, Org, Elin, Padmanabhan, Sandosh, Palmas, Walter, Palotie, Aarno, Pattie, Alison, WJH Penninx, Brenda, Perola, Markus, Peters, Annette, Polasek, Ozren, Pramstaller, Peter P, Tri Nguyen, Quang, Raitakari, Olli T, Rettig, Rainer, Rice, Kenneth, Ridker, Paul M, Ried, Janina S, Riese, Harriëtte, Ripatti, Samuli, Robino, Antonietta, Rose, Lynda M, Rotter, Jerome I, Rudan, Igor, Ruggiero, Daniela, Saba, Yasaman, Sala, Cinzia F, Salomaa, Veikko, Samani, Nilesh J, Sarin, Antti-Pekka, Schmidt, Reinhold, Schmidt, Helena, Shrine, Nick, Siscovick, David, Smith, Albert V, Snieder, Harold, Sõber, Siim, Sorice, Rossella, Starr, John M, Stott, David J, Strachan, David P, Strawbridge, Rona J, Sundström, Johan, Swertz, Morris A, Taylor, Kent D, Teumer, Alexander, Tobin, Martin D, Tomaszewski, Maciej, Toniolo, Daniela, Traglia, Michela, Trompet, Stella, Tuomilehto, Jaakko, Tzourio, Christophe, Uitterlinden, André G, Vaez, Ahmad, van der Most, Peter J, van Duijn, Cornelia M, Verwoert, Germaine C, Vitart, Veronique, Völker, Uwe, Vollenweider, Peter, Vuckovic, Dragana, Watkins, Hugh, Wild, Sarah H, Willemsen, Gonneke, Wilson, James F, Wright, Alan F, Yao, Jie, Zemunik, Tatijana, Zhang, Weihua, Attia, John R, Butterworth, Adam S, Chasman, Daniel I, Conen, David, Cucca, Francesco, Danesh, John, Hayward, Caroline, Howson, Joanna MM, Laakso, Markku, Lakatta, Edward G, Langenberg, Claudia, Melander, Olle, Mook-Kanamori, Dennis O, Palmer, Colin NA, Risch, Lorenz, Scott, Robert A, Scott, Rodney J, Sever, Peter, Spector, Tim D, van der Harst, Pim, Wareham, Nicholas J, Zeggini, Eleftheria, Levy, Daniel, Munroe, Patricia B, Newton-Cheh, Christopher, Brown, Morris J, Metspalu, Andres, Psaty, Bruce M., Wain, Louise V, Elliott, Paul, Caulfield, Mark J, Gormley, Padhraig, Anttila, Verneri, Palta, Priit, Esko, Tonu, Pers, Tune H, Farh, Kai-How, Cuenca-Leon, Ester, Muona, Mikko, Furlotte, Nicholas A, Kurth, Tobias, Ingason, Andres, McMahon, George, Ligthart, Lannie, Terwindt, Gisela M, Kallela, Mikko, Freilinger, Tobias M, Ran, Caroline, Gordon, Scott G, Stam, Anine H, Steinberg, Stacy, Borck, Guntram, Koiranen, Markku, Quaye, Lydia, Adams, Hieab H H, Lehtimäki, Terho, Sarin, Antti-Pekka, Wedenoja, Juho, Hinds, David A, Buring, Julie E, Schürks, Markus, Ridker, Paul M, Gudlaug Hrafnsdottir, Maria, Stefansson, Hreinn, Ring, Susan M, Hottenga, Jouke-Jan, Penninx, Brenda W J H, Färkkilä, Markus, Artto, Ville, Kaunisto, Mari, Vepsäläinen, Salli, Malik, Rainer, Heath, Andrew C, Madden, Pamela A F, Martin, Nicholas G, Montgomery, Grant W, Kurki, Mitja I, Kals, Mart, Mägi, Reedik, Pärn, Kalle, Hämäläinen, Eija, Huang, Hailiang, Byrnes, Andrea E, Franke, Lude, Huang, Jie, Stergiakouli, Evie, Lee, Phil H, Sandor, Cynthia, Webber, Caleb, Cader, Zameel, Muller-Myhsok, Bertram, Schreiber, Stefan, Meitinger, Thomas, Eriksson, Johan G, Salomaa, Veikko, Heikkilä, Kauko, Loehrer, Elizabeth, Uitterlinden, Andre G, Hofman, Albert, van Duijn, Cornelia M, Cherkas, Lynn, Pedersen, Linda M, Stubhaug, Audun, Nielsen, Christopher S, Männikkö, Minna, Mihailov, Evelin, Milani, Lili, Göbel, Hartmut, Esserlind, Ann-Louise, Francke Christensen, Anne, Folkmann Hansen, Thomas, Werge, Thomas, Kaprio, Jaakko, Aromaa, Arpo J, Raitakari, Olli, Arfan Ikram, M, Spector, Tim, Järvelin, Marjo-Riitta, Metspalu, Andres, Kubisch, Christian, Strachan, David P, Ferrari, Michel D, Belin, Andrea C, Dichgans, Martin, Wessman, Maija, van den Maagdenberg, Arn M J M, Boomsma, Dorret I, Davey Smith, George, Stefansson, Kari, Eriksson, Nicholas, Daly, Mark J, Neale, Benjamin M, Olesen, Jes, Chasman, Daniel I, Nyholt, Dale R, Palotie, Aarno, Akiyama, Masato, Alg, Varinder S., Børte, Sigrid, Broderick, Joseph P., Brumpton, Ben M., Dauvillier, Jérôme, Desal, Hubert, Dina, Christian, Friedrich, Christoph M., Gaál-Paavola, Emília I., Gentric, Jean-Christophe, Hirsch, Sven, Hostettler, Isabel C., Houlden, Henry, Hveem, Kristian, Jääskeläinen, Juha E., Johnsen, Marianne Bakke, Li, Liming, Lin, Kuang, Lindgren, Antti, Martin, Olivier, Matsuda, Koichi, Millwood, Iona Y., Naggara, Olivier, Niemelä, Mika, Pera, Joanna, Redon, Richard, Rouleau, Guy A., Sandvei, Marie Søfteland, Schilling, Sabine, Shotar, Eimad, Slowik, Agnieszka, Terao, Chikashi, Verschuren, W. M. Monique, Walters, Robin G., Werring, David J., Willer, Cristen J., Woo, Daniel, Worrall, Bradford B., and Zhou, Sirui

Published
2023
Full Text
View/download PDF

8. Abstract 12681: GWAS Meta-Analysis in SCAD, a Women Predominant Ischemic Heart Disease, Reveals Common Variants and Genes Related to Artery Integrity and Tissue-Mediated Coagulation

Author

Adlam, David, BERRANDOU, Takiy E, Georges, Adrien, Nelson, Christopher P, Giannoulatou, Eleni, Ma, Lijiang, Blencowe, Montgomory, Turley, Tamiel, Yang, Min-Lee, Iismaa, Siiri, Tarr, Ingrid, Muller, David, Hesselson, Stephanie, Junday, Keerat, Fatkin, Diane, COMBARET, Nicolas, Saw, Jacqueline, Webb, Tom, Tweet, Marysia, Hayes, Sharonne N, Xia, Yang, Ganesh, Santhi, Olson, Timothy M, Kovacic, Jason C, Graham, Robert M, Samani, Nilesh J, and Bouatia-Naji, Nabila

Published
2022
Full Text
View/download PDF

9. Genetic investigation of fibromuscular dysplasia identifies risk loci and shared genetics with common cardiovascular diseases

Author

Georges, Adrien, Yang, Min-Lee, Berrandou, Takiy-Eddine, Bakker, Mark K., Dikilitas, Ozan, Kiando, Soto Romuald, Ma, Lijiang, Satterfield, Benjamin A., Sengupta, Sebanti, Yu, Mengyao, Deleuze, Jean-François, Dupré, Delia, Hunker, Kristina L., Kyryachenko, Sergiy, Liu, Lu, Sayoud-Sadeg, Ines, Amar, Laurence, Brummett, Chad M., Coleman, Dawn M., d’Escamard, Valentina, de Leeuw, Peter, Fendrikova-Mahlay, Natalia, Kadian-Dodov, Daniella, Li, Jun Z., Lorthioir, Aurélien, Pappaccogli, Marco, Prejbisz, Aleksander, Smigielski, Witold, Stanley, James C., Zawistowski, Matthew, Zhou, Xiang, Zöllner, Sebastian, Amouyel, Philippe, De Buyzere, Marc L., Debette, Stéphanie, Dobrowolski, Piotr, Drygas, Wojciech, Gornik, Heather L., Olin, Jeffrey W., Piwonski, Jerzy, Rietzschel, Ernst R., Ruigrok, Ynte M., Vikkula, Miikka, Warchol Celinska, Ewa, Januszewicz, Andrzej, Kullo, Iftikhar J., Azizi, Michel, Jeunemaitre, Xavier, Persu, Alexandre, Kovacic, Jason C., Ganesh, Santhi K., and Bouatia-Naji, Nabila

Published
2021
Full Text
View/download PDF

10. Genetic Study of PHACTR1 and Fibromuscular Dysplasia, Meta-Analysis and Effects on Clinical Features of Patients: The ARCADIA-POL Study

Author

Warchol-Celinska, Ewa, Berrandou, Takiy, Prejbisz, Aleksander, Georges, Adrien, Dupré, Delia, Januszewicz, Magdalena, Florczak, Elzbieta, Jozwik-Plebanek, Katarzyna, Dobrowolski, Piotr, Smigielski, Witold, Drygas, Wojciech, Kadziela, Jacek, Witkowski, Adam, Kabat, Marek, Szczerbo-Trojanowska, Malgorzata, Pappaccogli, Marco, Persu, Alexandre, Jeunemaitre, Xavier, Januszewicz, Andrzej, and Bouatia-Naji, Nabila

Published
2020
Full Text
View/download PDF

12. Genetic Risk Score for Intracranial Aneurysms:Prediction of Subarachnoid Hemorrhage and Role in Clinical Heterogeneity

Author

Bakker, Mark K., Kanning, Jos P., Abraham, Gad, Martinsen, Amy E., Winsvold, Bendik S., Zwart, John Anker, Bourcier, Romain, Sawada, Tomonobu, Koido, Masaru, Kamatani, Yoichiro, Morel, Sandrine, Amouyel, Philippe, Debette, Stéphanie, Bijlenga, Philippe, Berrandou, Takiy, Ganesh, Santhi K., Bouatia-Naji, Nabila, Jones, Gregory, Bown, Matthew, Rinkel, Gabriel J.E., Veldink, Jan H., Ruigrok, Ynte M., Kristoffersen, Espen S., Bakker, Mark K., Kanning, Jos P., Abraham, Gad, Martinsen, Amy E., Winsvold, Bendik S., Zwart, John Anker, Bourcier, Romain, Sawada, Tomonobu, Koido, Masaru, Kamatani, Yoichiro, Morel, Sandrine, Amouyel, Philippe, Debette, Stéphanie, Bijlenga, Philippe, Berrandou, Takiy, Ganesh, Santhi K., Bouatia-Naji, Nabila, Jones, Gregory, Bown, Matthew, Rinkel, Gabriel J.E., Veldink, Jan H., Ruigrok, Ynte M., and Kristoffersen, Espen S.

Published
2023

13. S-22-4: GENOME WIDE ASSOCIATION STUDY OF FIBROMUSCULAR DYSPLASIA REVEALS MECHANISTIC LINKS WITH BLOOD PRESSURE REGULATION AND OTHER VASCULAR DISEASES

Author

Georges, Adrien, primary, Yang, Min Lee, additional, Berrandou, Takiy Eddine, additional, Liu, Lu, additional, Sayed, Ines Sadoug, additional, Dikilitas, Ozan, additional, Vikkula, Mikka, additional, Januszewicz, Andrzej, additional, Kullo, Iftikhar J, additional, Azizi, Michel, additional, Jeunemaitre, Xavier, additional, Persu, Alexandre, additional, Kovacic, Jason C, additional, Ganesh, Santhi K, additional, and Naji, Nabila Bouatia, additional

Published
2023
Full Text
View/download PDF

17. Author Correction: Genetic investigation of fibromuscular dysplasia identifies risk loci and shared genetics with common cardiovascular diseases.

Author

UCL - SSS/IREC/CARD - Pôle de recherche cardiovasculaire, UCL - (SLuc) Département cardiovasculaire, Georges, Adrien, Yang, Min-Lee, Berrandou, Takiy-Eddine, Bakker, Mark K, Dikilitas, Ozan, Kiando, Soto Romuald, Ma, Lijiang, Satterfield, Benjamin A, Sengupta, Sebanti, Yu, Mengyao, Deleuze, Jean-François, Dupré, Delia, Hunker, Kristina L, Kyryachenko, Sergiy, Liu, Lu, Sayoud-Sadeg, Ines, Amar, Laurence, Brummett, Chad M, Coleman, Dawn M, d'Escamard, Valentina, de Leeuw, Peter, Fendrikova-Mahlay, Natalia, Kadian-Dodov, Daniella, Li, Jun Z, Lorthioir, Aurélien, Pappaccogli, Marco, Prejbisz, Aleksander, Smigielski, Witold, Stanley, James C, Zawistowski, Matthew, Zhou, Xiang, Zöllner, Sebastian, FEIRI investigators, International Stroke Genetics Consortium (ISGC) Intracranial Aneurysm Working Group, MEGASTROKE, Amouyel, Philippe, De Buyzere, Marc L, Debette, Stéphanie, Dobrowolski, Piotr, Drygas, Wojciech, Gornik, Heather L, Olin, Jeffrey W, Piwonski, Jerzy, Rietzschel, Ernst R, Ruigrok, Ynte M, Vikkula, Miikka, Warchol Celinska, Ewa, Januszewicz, Andrzej, Kullo, Iftikhar J, Azizi, Michel, ARCADIA Investigators, Jeunemaitre, Xavier, Persu, Alexandre, Kovacic, Jason C, Ganesh, Santhi K, Bouatia-Naji, Nabila, UCL - SSS/IREC/CARD - Pôle de recherche cardiovasculaire, UCL - (SLuc) Département cardiovasculaire, Georges, Adrien, Yang, Min-Lee, Berrandou, Takiy-Eddine, Bakker, Mark K, Dikilitas, Ozan, Kiando, Soto Romuald, Ma, Lijiang, Satterfield, Benjamin A, Sengupta, Sebanti, Yu, Mengyao, Deleuze, Jean-François, Dupré, Delia, Hunker, Kristina L, Kyryachenko, Sergiy, Liu, Lu, Sayoud-Sadeg, Ines, Amar, Laurence, Brummett, Chad M, Coleman, Dawn M, d'Escamard, Valentina, de Leeuw, Peter, Fendrikova-Mahlay, Natalia, Kadian-Dodov, Daniella, Li, Jun Z, Lorthioir, Aurélien, Pappaccogli, Marco, Prejbisz, Aleksander, Smigielski, Witold, Stanley, James C, Zawistowski, Matthew, Zhou, Xiang, Zöllner, Sebastian, FEIRI investigators, International Stroke Genetics Consortium (ISGC) Intracranial Aneurysm Working Group, MEGASTROKE, Amouyel, Philippe, De Buyzere, Marc L, Debette, Stéphanie, Dobrowolski, Piotr, Drygas, Wojciech, Gornik, Heather L, Olin, Jeffrey W, Piwonski, Jerzy, Rietzschel, Ernst R, Ruigrok, Ynte M, Vikkula, Miikka, Warchol Celinska, Ewa, Januszewicz, Andrzej, Kullo, Iftikhar J, Azizi, Michel, ARCADIA Investigators, Jeunemaitre, Xavier, Persu, Alexandre, Kovacic, Jason C, Ganesh, Santhi K, and Bouatia-Naji, Nabila

Abstract

No abstract available

Published
2022

19. National French registry of spontaneous coronary artery dissections: prevalence of fibromuscular dysplasia and genetic analyses: National French SCAD registry: DISCO

Author

Combaret, Nicolas, Gerbaud, Edouard, Dérimay, François, Souteyrand, Geraud, Cassagnes, Lucie, Bouajila, Sara, Berrandou, Takiy, Rangé, Gregoire, Meneveau, Nicolas, Harbaoui, Brahim, Lattuca, Benoit, Bouatia-Naji, Nabila, and Motreff, Pascal

Subjects
Clinical Research
Abstract

BACKGROUND: Spontaneous coronary artery dissection (SCAD) is an increasingly reported but poorly understood condition. Few European data are available. AIMS: The aims of this study were to obtain European data on SCAD, determine the prevalence of fibromuscular dysplasia (FMD) and enable genetic analyses in this population. METHODS: Data from a national French registry of SCAD cases were analysed prospectively and retrospectively. Clinical and angiographic data and management strategy were collected. Major adverse cardiovascular events (MACE) were analysed after one year of follow-up. Subjects were screened for FMD and blood was collected for DNA extraction. RESULTS: From June 2016 to August 2018, 373 SCAD cases were confirmed by the core lab. Mean age was 51.5 years. Patients were mostly women (90.6%) and 54.7% of cases had less than two cardiovascular risk factors. At one year, 295 patients (79.1%) were treated conservatively, the MACE rate was 12.3%, and there were no cases of mortality. The recurrence rate of SCAD was 3.3%. FMD was found at ≥1 arterial site in 45.0% of cases. We also confirmed the genetic association between the PHACTR1 locus and SCAD (odds ratio=1.66, p=7.08×10–8). CONCLUSIONS: Here we describe the DISCO registry, the largest European SCAD cohort where FMD was found in 45% of cases and the genetic association with PHACTR1 was confirmed. This nationwide cohort is a valuable resource for future clinical and genetic investigation to understand SCAD aetiology.

Published
2021

20. National French registry of spontaneous coronary artery dissections: prevalence of fibromuscular dysplasia and genetic analyses

Author

Combaret, Nicolas, primary, Gerbaud, Edouard, additional, Dérimay, François, additional, Souteyrand, Geraud, additional, Cassagnes, Lucie, additional, Bouajila, Sara, additional, Berrandou, Takiy, additional, Rangé, Gregoire, additional, Meneveau, Nicolas, additional, Harbaoui, Brahim, additional, Lattuca, Benoit, additional, Bouatia-Naji, Nabila, additional, and Motreff, Pascal, additional

Published
2021
Full Text
View/download PDF

21. Genetic investigation of fibromuscular dysplasia identifies risk loci and shared genetics with common cardiovascular diseases.

Author

UCL - SSS/DDUV/GEHU - Génétique, UCL - SSS/IREC/CARD - Pôle de recherche cardiovasculaire, UCL - (SLuc) Département cardiovasculaire, Georges, Adrien, Yang, Min-Lee, Berrandou, Takiy-Eddine, Bakker, Mark K, Dikilitas, Ozan, Kiando, Soto Romuald, Ma, Lijiang, Satterfield, Benjamin A, Sengupta, Sebanti, Yu, Mengyao, Deleuze, Jean-François, Dupré, Delia, Hunker, Kristina L, Kyryachenko, Sergiy, Liu, Lu, Sayoud-Sadeg, Ines, Amar, Laurence, Brummett, Chad M, Coleman, Dawn M, d'Escamard, Valentina, de Leeuw, Peter, Fendrikova-Mahlay, Natalia, Kadian-Dodov, Daniella, Li, Jun Z, Lorthioir, Aurélien, Pappaccogli, Marco, Prejbisz, Aleksander, Smigielski, Witold, Stanley, James C, Zawistowski, Matthew, Zhou, Xiang, Zöllner, Sebastian, FEIRI investigators, International Stroke Genetics Consortium (ISGC) Intracranial Aneurysm Working Group, MEGASTROKE, Amouyel, Philippe, De Buyzere, Marc L, Debette, Stéphanie, Dobrowolski, Piotr, Drygas, Wojciech, Gornik, Heather L, Olin, Jeffrey W, Piwonski, Jerzy, Rietzschel, Ernst R, Ruigrok, Ynte M, Vikkula, Miikka, Warchol Celinska, Ewa, Januszewicz, Andrzej, Kullo, Iftikhar J, Azizi, Michel, Jeunemaitre, Xavier, Persu, Alexandre, Kovacic, Jason C, Ganesh, Santhi K, Bouatia-Naji, Nabila, UCL - SSS/DDUV/GEHU - Génétique, UCL - SSS/IREC/CARD - Pôle de recherche cardiovasculaire, UCL - (SLuc) Département cardiovasculaire, Georges, Adrien, Yang, Min-Lee, Berrandou, Takiy-Eddine, Bakker, Mark K, Dikilitas, Ozan, Kiando, Soto Romuald, Ma, Lijiang, Satterfield, Benjamin A, Sengupta, Sebanti, Yu, Mengyao, Deleuze, Jean-François, Dupré, Delia, Hunker, Kristina L, Kyryachenko, Sergiy, Liu, Lu, Sayoud-Sadeg, Ines, Amar, Laurence, Brummett, Chad M, Coleman, Dawn M, d'Escamard, Valentina, de Leeuw, Peter, Fendrikova-Mahlay, Natalia, Kadian-Dodov, Daniella, Li, Jun Z, Lorthioir, Aurélien, Pappaccogli, Marco, Prejbisz, Aleksander, Smigielski, Witold, Stanley, James C, Zawistowski, Matthew, Zhou, Xiang, Zöllner, Sebastian, FEIRI investigators, International Stroke Genetics Consortium (ISGC) Intracranial Aneurysm Working Group, MEGASTROKE, Amouyel, Philippe, De Buyzere, Marc L, Debette, Stéphanie, Dobrowolski, Piotr, Drygas, Wojciech, Gornik, Heather L, Olin, Jeffrey W, Piwonski, Jerzy, Rietzschel, Ernst R, Ruigrok, Ynte M, Vikkula, Miikka, Warchol Celinska, Ewa, Januszewicz, Andrzej, Kullo, Iftikhar J, Azizi, Michel, Jeunemaitre, Xavier, Persu, Alexandre, Kovacic, Jason C, Ganesh, Santhi K, and Bouatia-Naji, Nabila

Abstract

Fibromuscular dysplasia (FMD) is an arteriopathy associated with hypertension, stroke and myocardial infarction, affecting mostly women. We report results from the first genome-wide association meta-analysis of six studies including 1556 FMD cases and 7100 controls. We find an estimate of SNP-based heritability compatible with FMD having a polygenic basis, and report four robustly associated loci (PHACTR1, LRP1, ATP2B1, and LIMA1). Transcriptome-wide association analysis in arteries identifies one additional locus (SLC24A3). We characterize open chromatin in arterial primary cells and find that FMD associated variants are located in arterial-specific regulatory elements. Target genes are broadly involved in mechanisms related to actin cytoskeleton and intracellular calcium homeostasis, central to vascular contraction. We find significant genetic overlap between FMD and more common cardiovascular diseases and traits including blood pressure, migraine, intracranial aneurysm, and coronary artery disease.

Published
2021

22. GENETIC ASSOCIATION STUDIES OF FIBROMUSCULAR DYSPLASIA IDENTIFY NEW RISK LOCI AND SHARED GENETIC BASIS WITH MORE COMMON VASCULAR DISEASES

Author

Georges, Adrien, primary, Yang, Min-Lee, additional, Berrandou, Takiy-Eddine, additional, Bakker, Mark, additional, Dikilitas, Ozan, additional, Ma, Lijiang, additional, Satterfield, Benjamin A., additional, Sengupta, Sebanti, additional, Hunker, Kristina L., additional, Amar, Laurence, additional, Lorthioir, Aurélien, additional, Prejbisz, Aleksander, additional, Pappaccogli, Marco, additional, Ruigrok, Ynte, additional, Olin, Jeffrey W., additional, Gornik, Heather L., additional, Rietzschel, Ernst R., additional, Celinska, Ewa Warchol, additional, Januszewicz, Andrzej, additional, Kullo, Iftikhar J., additional, Azizi, Michel, additional, Jeunemaitre, Xavier, additional, Persu, Alexandre, additional, Kovacic, Jason C., additional, Ganesh, Santhi K., additional, and Bouatia-Naji, Nabila, additional

Published
2021
Full Text
View/download PDF

23. RARE LOSS-OF-FUNCTION MUTATIONS OF PTGIR IDENTIFIED IN FIBROMUSCULAR DYSPLASIA AND SPONTANEOUS CORONARY ARTERY DISSECTION

Author

Georges, Adrien, primary, Albuisson, Juliette, additional, Berrandou, Takiy, additional, Dupré, Délia, additional, Lorthioir, Aurélien, additional, Amar, Laurence, additional, Januszewicz, Andrzej, additional, Motreff, Pascal, additional, Adlam, David, additional, Azizi, Michel, additional, Gornik, Heather, additional, Ganesh, Santhi, additional, Kovacic, Jason, additional, Jeunemaitre, Xavier, additional, and Bouatia-Naji, Nabila, additional

Published
2021
Full Text
View/download PDF

25. Rare loss-of-function mutations of PTGIR are enriched in fibromuscular dysplasia

Author

Georges, Adrien, primary, Albuisson, Juliette, additional, Berrandou, Takiy, additional, Dupré, Délia, additional, Lorthioir, Aurélien, additional, D’Escamard, Valentina, additional, Di Narzo, Antonio F, additional, Kadian-Dodov, Daniella, additional, Olin, Jeffrey W, additional, Warchol-Celinska, Ewa, additional, Prejbisz, Aleksander, additional, Januszewicz, Andrzej, additional, Bruneval, Patrick, additional, Baranowska, Anna A, additional, Webb, Tom R, additional, Hamby, Stephen E, additional, Samani, Nilesh J, additional, Adlam, David, additional, Fendrikova-Mahlay, Natalia, additional, Hazen, Stanley, additional, Wang, Yu, additional, Yang, Min-Lee, additional, Hunker, Kristina, additional, Combaret, Nicolas, additional, Motreff, Pascal, additional, Chédid, Antoine, additional, Fiquet, Béatrice, additional, Plouin, Pierre-François, additional, Mousseaux, Elie, additional, Azarine, Arshid, additional, Amar, Laurence, additional, Azizi, Michel, additional, Gornik, Heather L, additional, Ganesh, Santhi K, additional, Kovacic, Jason C, additional, Jeunemaitre, Xavier, additional, and Bouatia-Naji, Nabila, additional

Published
2020
Full Text
View/download PDF

26. Characterization of genomic regulation profiles in human mitral valve whole tissue to annotate genetic risk loci for mitral valve prolapse

Author

Kyryachenko, Sergiy, primary, Georges, Adrien, additional, Yu, Mengyao, additional, Berrandou, Takiy E., additional, Bruneval, Patrick, additional, Rubio, Tony, additional, Gronwald, Judith, additional, Baraki, Hassina, additional, Kutschka, Ingo, additional, Norris, Russell A, additional, Voight, Niels, additional, and Bouatia-Naji, Nabila, additional

Published
2020
Full Text
View/download PDF

27. Genetic Study of and Fibromuscular Dysplasia, Meta-Analysis and Effects on Clinical Features of Patients: The ARCADIA-POL Study

Author

Warchol-Celinska, Ewa, Berrandou, Takiy, Prejbisz, Aleksander, Georges, Adrien, Dupré, Delia, Januszewicz, Magdalena, Florczak, Elzbieta, Jozwik-Plebanek, Katarzyna, Dobrowolski, Piotr, Smigielski, Witold, Drygas, Wojciech, Kadziela, Jacek, Witkowski, Adam, Kabat, Marek, Szczerbo-Trojanowska, Malgorzata, Pappaccogli, Marco, Persu, Alexandre, Jeunemaitre, Xavier, Januszewicz, Andrzej, Bouatia-Naji, Nabila, UCL - SSS/IREC/CARD - Pôle de recherche cardiovasculaire, UCL - (SLuc) Département cardiovasculaire, and UCL - (SLuc) Service de pathologie cardiovasculaire

Subjects
Adult, Male, Genotype, Computed Tomography Angiography, Microfilament Proteins, Headache, fibromuscular dysplasia, Middle Aged, Aneurysm, Dizziness, Polymorphism, Single Nucleotide, stroke, Tinnitus, Hypertension, Renovascular, myocardial infarction, Hypertension, cardiovascular system, Humans, risk factors, Female, Genetic Predisposition to Disease, cardiovascular diseases, Registries, Contraceptives, Oral
Abstract

Fibromuscular dysplasia (FMD) is a common cause of renovascular hypertension in middle-aged women lacking cardiovascular risk factors. FMD is an intriguing group of noninflammatory arterial deformations, which results in stenosis, and in some cases, aneurysms and dissections of medium-sized arteries. Mostly asymptomatic, the clinical manifestations of FMD depends on the arterial bed affected and is usually diagnosed in the context of resistant hypertension or after a stroke, particularly cervical artery dissection. FMD is increasingly identified after the occurrence of spontaneous coronary artery dissection, an underdiagnosed cause of acute myocardial infarction. We have previously established a complex genetic basis for FMD and reported a first genetic susceptibility locus on chromosome 6 involving rs9349379, a common genetic locus within the phosphatase and active regulatory 1 gene (PHACTR1). This pleiotropic genetic locus is also known to associate with several neurovascular diseases, atherosclerotic acute myocardial infarction, and spontaneous coronary artery dissection. [...]

Published
2020

28. Xenobiotic Metabolism Genes : Prediction of Biological Contamination Levels by Environmental Pollutants and Implication in Breast Cancer Risk. Analysis of the CECILE Study

Author

Berrandou, Takiy Eddine, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Saclay (COmUE), Pascal Guénel, and STAR, ABES

Subjects
[SDV.GEN]Life Sciences [q-bio]/Genetics, Polluants organochlorés persistants, Gene-environment interactions, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.GEN] Life Sciences [q-bio]/Genetics, Tabagisme, Gènes du métabolisme des xénobiotiques, Active smoking, Persistent organochlorine pollutants, Breast cancer, [SDV.CAN] Life Sciences [q-bio]/Cancer, Interactions gènes-environnement, Xenobiotic metabolism genes, Cancer du sein
Abstract

The xenobiotic metabolism (XM) genes involved in the activation and elimination of environmental carcinogens may modulate breast cancer risk, but their effects in breast cancer have been little studied and are poorly understood. The objectives of the PhD were to study the role of XM genes in breast cancer on the one hand, and in the biological levels of suspected breast carcinogens on the other. The analyses were based on a population-based case-control study on breast cancer (CECILE study). We investigated the association of breast cancer (1) with NAT2 gene variants that determine the type of slow or rapid acetylator in each individual; (2) with polymorphisms of XM genes that were studied jointly at the gene and at the XM pathway level using a gene set method. In each of these approaches, interactions with tobacco consumption were studied. In a final section, we sought to identify polymorphisms of XM genes that predict blood concentrations of persistent organochlorine pollutants (p,p'-DDE and PCB153) among the controls of the CECILE study.The risk of breast cancer was increased in women with a NAT2 genetic profile of rapid acetylators compared to women with a profile of slow acetylators. Among slow acetylators, current smokers had an increased risk of breast cancer compared to non-smokers, indicating an interaction between tobacco smoking and NAT2 genotype. The gene set approach showed that polymorphisms at the level of some XM genes and at the level of the entire pathway were collectively associated with breast cancer. The association between breast cancer and all pathway XM polymorphisms was observed in female smokers, indicating a role for tobacco smoking in this association. Finally, we have shown that CYP2B6 gene was a determinant of blood levels of p,p'-DDE and PCB153. Our results highlight a role of XM genes in breast cancer that is explained by their function in the metabolism and elimination of environmental carcinogens., Les gènes du métabolisme des xénobiotiques (MX) impliqués dans l’activation et l’élimination des cancérogènes environnementaux pourraient moduler le risque de cancer du sein, mais leurs effets dans ce cancer ont été peu étudiés et sont mal connus. Les objectifs de la thèse étaient d’étudier le rôle des gènes MX dans le cancer du sein d’une part, et dans les niveaux biologiques de cancérogènes mammaires suspectés, d’autre part. Les analyses ont porté sur les données d’une étude cas-témoins en population sur les cancers du sein (étude CECILE). L’association avec le cancer du sein a été étudiée (1) avec les variants du gène NAT2 qui déterminent le type d’acétyleur lent ou rapide de chaque individu ; (2) les polymorphismes des gènes MX étudiés conjointement au niveau de chacun des gènes et au niveau de l’ensemble du pathway à l’aide d’une méthode exploratoire de type « gene-set ». Dans chacune de ces approches, les interactions avec la consommation de tabac ont été étudiées. Dans une dernière partie, nous avons cherché à identifier les polymorphismes des gènes MX prédictifs des concentrations sanguines de polluants organochlorés persistants (p,p’-DDE et PCB153) chez les témoins de l’étude CECILE. Le risque de cancer du sein était augmenté chez les femmes ayant un profil génétique NAT2 d’acétyleuses rapides par rapport aux femmes ayant un profil d’acétyleuses lentes. Parmi les acétyleuses lentes, les femmes fumeuses avaient un risque de cancer du sein augmenté par rapport aux non fumeuses indiquant l’existence d’une interaction tabac-NAT2. L’approche « gene-set » montrait que les polymorphismes au niveau de plusieurs gènes MX et au niveau de l’ensemble du pathway étaient associés collectivement au cancer du sein. L’association entre le cancer du sein et l’ensemble des polymorphismes du pathway XM était observée chez les fumeuses, indiquant le rôle de la consommation de tabac dans cette association. Enfin, nous avons montré l’effet du gène CYP2B6 en tant que déterminant des niveaux sanguins de p,p’-DDE et PCB153. Nos résultats mettent en évidence un rôle des gènes XM dans le cancer du sein qui peut être expliqué par leur fonction dans le métabolisme et l’élimination des cancérogènes environnementaux.

Published
2018

29. Gènes du métabolisme des xénobiotiques : rôle prédictif dans les niveaux de contamination biologique par les polluants environnementaux et implication dans le risque de cancer du sein. Analyse de l’étude CECILE

Author

Berrandou, Takiy Eddine, Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Université Paris Saclay (COmUE), and Pascal Guénel

Subjects
[SDV.GEN]Life Sciences [q-bio]/Genetics, Breast cancer, Interactions gènes-environnement, Polluants organochlorés persistants, Xenobiotic metabolism genes, Gene-environment interactions, [SDV.CAN]Life Sciences [q-bio]/Cancer, Tabagisme, Gènes du métabolisme des xénobiotiques, Cancer du sein, Active smoking, Persistent organochlorine pollutants
Abstract

The xenobiotic metabolism (XM) genes involved in the activation and elimination of environmental carcinogens may modulate breast cancer risk, but their effects in breast cancer have been little studied and are poorly understood. The objectives of the PhD were to study the role of XM genes in breast cancer on the one hand, and in the biological levels of suspected breast carcinogens on the other. The analyses were based on a population-based case-control study on breast cancer (CECILE study). We investigated the association of breast cancer (1) with NAT2 gene variants that determine the type of slow or rapid acetylator in each individual; (2) with polymorphisms of XM genes that were studied jointly at the gene and at the XM pathway level using a gene set method. In each of these approaches, interactions with tobacco consumption were studied. In a final section, we sought to identify polymorphisms of XM genes that predict blood concentrations of persistent organochlorine pollutants (p,p'-DDE and PCB153) among the controls of the CECILE study.The risk of breast cancer was increased in women with a NAT2 genetic profile of rapid acetylators compared to women with a profile of slow acetylators. Among slow acetylators, current smokers had an increased risk of breast cancer compared to non-smokers, indicating an interaction between tobacco smoking and NAT2 genotype. The gene set approach showed that polymorphisms at the level of some XM genes and at the level of the entire pathway were collectively associated with breast cancer. The association between breast cancer and all pathway XM polymorphisms was observed in female smokers, indicating a role for tobacco smoking in this association. Finally, we have shown that CYP2B6 gene was a determinant of blood levels of p,p'-DDE and PCB153. Our results highlight a role of XM genes in breast cancer that is explained by their function in the metabolism and elimination of environmental carcinogens.; Les gènes du métabolisme des xénobiotiques (MX) impliqués dans l’activation et l’élimination des cancérogènes environnementaux pourraient moduler le risque de cancer du sein, mais leurs effets dans ce cancer ont été peu étudiés et sont mal connus. Les objectifs de la thèse étaient d’étudier le rôle des gènes MX dans le cancer du sein d’une part, et dans les niveaux biologiques de cancérogènes mammaires suspectés, d’autre part. Les analyses ont porté sur les données d’une étude cas-témoins en population sur les cancers du sein (étude CECILE). L’association avec le cancer du sein a été étudiée (1) avec les variants du gène NAT2 qui déterminent le type d’acétyleur lent ou rapide de chaque individu ; (2) les polymorphismes des gènes MX étudiés conjointement au niveau de chacun des gènes et au niveau de l’ensemble du pathway à l’aide d’une méthode exploratoire de type « gene-set ». Dans chacune de ces approches, les interactions avec la consommation de tabac ont été étudiées. Dans une dernière partie, nous avons cherché à identifier les polymorphismes des gènes MX prédictifs des concentrations sanguines de polluants organochlorés persistants (p,p’-DDE et PCB153) chez les témoins de l’étude CECILE. Le risque de cancer du sein était augmenté chez les femmes ayant un profil génétique NAT2 d’acétyleuses rapides par rapport aux femmes ayant un profil d’acétyleuses lentes. Parmi les acétyleuses lentes, les femmes fumeuses avaient un risque de cancer du sein augmenté par rapport aux non fumeuses indiquant l’existence d’une interaction tabac-NAT2. L’approche « gene-set » montrait que les polymorphismes au niveau de plusieurs gènes MX et au niveau de l’ensemble du pathway étaient associés collectivement au cancer du sein. L’association entre le cancer du sein et l’ensemble des polymorphismes du pathway XM était observée chez les fumeuses, indiquant le rôle de la consommation de tabac dans cette association. Enfin, nous avons montré l’effet du gène CYP2B6 en tant que déterminant des niveaux sanguins de p,p’-DDE et PCB153. Nos résultats mettent en évidence un rôle des gènes XM dans le cancer du sein qui peut être expliqué par leur fonction dans le métabolisme et l’élimination des cancérogènes environnementaux.

Published
2018

30. Rare Loss-of-function Mutations ofPTGIRIdentified in Fibromuscular Dysplasia and Spontaneous Coronary Artery Dissection

Author

Georges, Adrien, primary, Albuisson, Juliette, additional, Berrandou, Takiy, additional, Dupré, Délia, additional, Lorthioir, Aurélien, additional, D’Escamard, Valentina, additional, Di Narzo, Antonio F, additional, Kadian-Dodov, Daniella, additional, Olin, Jeffrey W, additional, Warchol-Celinska, Ewa, additional, Prejbisz, Aleksander, additional, Januszewicz, Andrzej, additional, Bruneval, Patrick, additional, Baranowska, Anna A., additional, Webb, Tom R., additional, Hamby, Stephen E., additional, Samani, Nilesh J., additional, Adlam, David, additional, Fendrikova-Mahlay, Natalia, additional, Hazen, Stanley, additional, Wang, Yu, additional, Yang, Min-Lee, additional, Hunker, Kristina, additional, Combaret, Nicolas, additional, Motreff, Pascal, additional, Chédid, Antoine, additional, Fiquet, Béatrice, additional, Plouin, Pierre-François, additional, Mousseaux, Elie, additional, Azarine, Arshid, additional, Amar, Laurence, additional, Azizi, Michel, additional, Gornik, Heather L., additional, Ganesh, Santhi K., additional, Kovacic, Jason C., additional, Jeunemaitre, Xavier, additional, and Bouatia-Naji, Nabila, additional

Published
2019
Full Text
View/download PDF

31. Rare loss-of-function mutations of PTGIR are enriched in fibromuscular dysplasia.

Author

Georges, Adrien, Albuisson, Juliette, Berrandou, Takiy, Dupré, Délia, Lorthioir, Aurélien, D'Escamard, Valentina, Narzo, Antonio F Di, Kadian-Dodov, Daniella, Olin, Jeffrey W, Warchol-Celinska, Ewa, Prejbisz, Aleksander, Januszewicz, Andrzej, Bruneval, Patrick, Baranowska, Anna A, Webb, Tom R, Hamby, Stephen E, Samani, Nilesh J, Adlam, David, Fendrikova-Mahlay, Natalia, and Hazen, Stanley

Subjects
FIBRODYSPLASIA ossificans progressiva, GENETIC mutation, DYSPLASIA, PROSTAGLANDIN receptors, MIDDLE-aged women, ARTERIAL diseases
Abstract

Aims Fibromuscular dysplasia (FMD) and spontaneous coronary artery dissection (SCAD) are related, non-atherosclerotic arterial diseases mainly affecting middle-aged women. Little is known about their physiopathological mechanisms. We aimed to identify rare genetic causes to elucidate molecular mechanisms implicated in FMD and SCAD. Methods and results We analysed 29 exomes that included familial and sporadic FMD. We identified one rare loss-of-function variant (LoF) (frequencygnomAD = 0.000075) shared by two FMD sisters in the prostaglandin I2 receptor gene (PTGIR), a key player in vascular remodelling. Follow-up was conducted by targeted or Sanger sequencing (1071 FMD and 363 SCAD patients) or lookups in exome (264 FMD) or genome sequences (480 SCAD), all independent and unrelated. It revealed four additional LoF allele carriers, in addition to several rare missense variants, among FMD patients, and two LoF allele carriers among SCAD patients, including one carrying a rare splicing mutation (c.768 + 1C>G). We used burden test to test for enrichment in patients compared to gnomAD controls, which detected a putative enrichment in FMD (P TRAPD = 8 × 10−4), but not a significant enrichment (P TRAPD = 0.12) in SCAD. The biological effects of variants on human prostaclycin receptor (hIP) signalling and protein expression were characterized using transient overexpression in human cells. We confirmed the LoFs (Q163X and P17RfsX6) and one missense (L67P), identified in one FMD and one SCAD patient, to severely impair hIP function in vitro. Conclusions Our study shows that rare genetic mutations in PTGIR are enriched among FMD patients and found in SCAD patients, suggesting a role for prostacyclin signalling in non-atherosclerotic stenosis and dissection. [ABSTRACT FROM AUTHOR]

Published
2021
Full Text
View/download PDF

34. Association of breast cancer risk with polymorphisms in genes involved in the metabolism of xenobiotics and interaction with tobacco smoking: A gene‐set analysis.

Author

Berrandou, Takiy, Mulot, Claire, Cordina‐Duverger, Emilie, Arveux, Patrick, Laurent‐Puig, Pierre, Truong, Thérèse, and Guénel, Pascal

Abstract

Single nucleotide polymorphisms (SNPs) in genes involved in xenobiotics metabolism (XM) are suspected to play a role in breast cancer risk. However, previous findings based on a SNP by SNP approach need to be replicated taking into account the combined effects of multiple SNPs. We used a gene‐set analysis method to study the association between breast cancer risk and genetic variation in XM genes (seen as a set of SNPs) and in the XM pathway (seen as a set of genes). We also studied the interaction between variants in XM genes and tobacco smoking. The analysis was conducted in a case–control study of 1,125 cases and 1,172 controls. Using a dedicated chip, genotyping data of 585 SNPs in 68 XM genes were available. Genetic variation in the whole XM pathway was significantly associated with premenopausal breast cancer risk (p = 0.008). This association was mainly driven by genetic variation in NAT2, CYP2C18, CYP2C19, AKR1C2 and ALDH1A3. The association between the XM gene pathway and breast cancer was observed among current and previous smokers, but not among never smokers (p = 0.013 for interaction between XM genes and tobacco smoking status). The association with breast cancer risk indicates that XM genes variants may play a role in breast carcinogenesis through their detoxification function of environmental pollutants, such as those contained in tobacco smoke. What's new? While environmental chemicals are risk factors for breast cancer, little is known about whether their role in cancer etiology is influenced by variations in genes involved in carcinogen breakdown via xenobiotic metabolism (XM). To investigate this question, the authors of the present study analyzed interactions between XM genes and tobacco smoking among breast cancer patients. Among ever‐smokers, single nucleotide polymorphisms in XM genes were associated with premenopausal breast cancer. The association was absent among never smokers. The authors conclude that XM gene variants likely modulate breast cancer risk associated with exposure to tobacco smoke, which contains thousands of toxic chemicals. [ABSTRACT FROM AUTHOR]

Published
2019
Full Text
View/download PDF

35. Rare loss-of-function mutations of PTGIR are enriched in fibromuscular dysplasia

Author

Georges, Adrien, Albuisson, Juliette, Berrandou, Takiy, Dupré, Délia, Lorthioir, Aurélien, D’Escamard, Valentina, Di Narzo, Antonio F, Kadian-Dodov, Daniella, Olin, Jeffrey W, Warchol-Celinska, Ewa, Prejbisz, Aleksander, Januszewicz, Andrzej, Bruneval, Patrick, Baranowska, Anna A, Webb, Tom R, Hamby, Stephen E, Samani, Nilesh J, Adlam, David, Fendrikova-Mahlay, Natalia, Hazen, Stanley, Wang, Yu, Yang, Min-Lee, Hunker, Kristina, Combaret, Nicolas, Motreff, Pascal, Chédid, Antoine, Fiquet, Béatrice, Plouin, Pierre-François, Mousseaux, Elie, Azarine, Arshid, Amar, Laurence, Azizi, Michel, Gornik, Heather L, Ganesh, Santhi K, Kovacic, Jason C, Jeunemaitre, Xavier, Bouatia-Naji, Nabila, Institut Pascal (IP), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-Institut national polytechnique Clermont Auvergne (INP Clermont Auvergne), and Université Clermont Auvergne (UCA)-Université Clermont Auvergne (UCA)

Subjects
Adult, Male, [SDV]Life Sciences [q-bio], Coronary Vessel Anomalies, DNA Mutational Analysis, Mutation, Missense, Receptors, Epoprostenol, Risk Assessment, Renal Artery, Prostacyclin signalling, Loss of Function Mutation, Predictive Value of Tests, Risk Factors, Databases, Genetic, Genetics, Fibromuscular Dysplasia, Humans, AcademicSubjects/MED00200, Genetic Predisposition to Disease, Vascular Diseases, Aged, Australia, Rare loss-of-function variants, Original Articles, Spontaneous coronary artery dissection, Middle Aged, United States, Europe, HEK293 Cells, Phenotype, Female, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Aims Fibromuscular dysplasia (FMD) and spontaneous coronary artery dissection (SCAD) are related, non-atherosclerotic arterial diseases mainly affecting middle-aged women. Little is known about their physiopathological mechanisms. We aimed to identify rare genetic causes to elucidate molecular mechanisms implicated in FMD and SCAD. Methods and results We analysed 29 exomes that included familial and sporadic FMD. We identified one rare loss-of-function variant (LoF) (frequencygnomAD = 0.000075) shared by two FMD sisters in the prostaglandin I2 receptor gene (PTGIR), a key player in vascular remodelling. Follow-up was conducted by targeted or Sanger sequencing (1071 FMD and 363 SCAD patients) or lookups in exome (264 FMD) or genome sequences (480 SCAD), all independent and unrelated. It revealed four additional LoF allele carriers, in addition to several rare missense variants, among FMD patients, and two LoF allele carriers among SCAD patients, including one carrying a rare splicing mutation (c.768 + 1C>G). We used burden test to test for enrichment in patients compared to gnomAD controls, which detected a putative enrichment in FMD (PTRAPD = 8 × 10−4), but not a significant enrichment (PTRAPD = 0.12) in SCAD. The biological effects of variants on human prostaclycin receptor (hIP) signalling and protein expression were characterized using transient overexpression in human cells. We confirmed the LoFs (Q163X and P17RfsX6) and one missense (L67P), identified in one FMD and one SCAD patient, to severely impair hIP function in vitro. Conclusions Our study shows that rare genetic mutations in PTGIR are enriched among FMD patients and found in SCAD patients, suggesting a role for prostacyclin signalling in non-atherosclerotic stenosis and dissection., Graphical Abstract

Full Text
View/download PDF

36. Abstract 13109: Epigenetic Regulation and Function of Pleiotropic GWAS Locus LRP1in Human Induced Pluripotent Stem Cells Derived Contractile Smooth Muscle Cells

Author

LIU, LU, ZAHRA HAIMOUD, Fatima, HENRY, Joséphine, BERRANDOU, Takiy, GEORGES, Adrien, and BOUATIA-NAJI, Nabila

Abstract

Introduction:Spontaneous coronary artery dissection (SCAD) is an increasingly recognized cause of myocardial infarction in young and middle-aged women. A common genetic variant, rs11172113, located in LRP1 (low density lipoprotein receptor-related protein 1) first intron, was associated with several vascular diseases, including SCAD, and regulation of LRP1 expression in arterial tissues. However, the biological mechanisms through which rs11172113 influence LRP1 function in the context of non-atherosclerotic arterial lesions are not known.Hypothesis:We hypothesized that rs11172113 genotype affects LRP1 expression through specific mechanisms in contractile smooth muscle cells (SMCs), leading to alterations of their physiological function.Methods:We differentiated 4 human induced pluripotent stem cells (iPSCs) lines (2 males, 2 females) towards either contractile or synthetic SMCs using a recently optimized 24-day protocol. We performed RNA-Seq and ATAC-Seq at 6 time points during differentiation. We silenced LRP1 using siRNAs in differentiated SMCs and used CRISPR-Cas9 to induce deletions of the enhancer region containing rs11172113 or frame-shift indels in exons 2 or 5 of LRP1 in iPSCs.Results:iPSCs derived SMCs presented the expected morphology and expression of SMC markers. Transcriptomic analyses showed that contractile SMCs harbored SMC properties during late differentiation and resembled SMCs of artery tissue, whereas genes involved in cell stress were upregulated in synthetic SMCs at the end of differentiation. In particular, LRP1 expression and DNA accessibility at rs11172113 were higher in contractile SMCs. The deletion of rs11172113 enhancer region led to a decrease in the expression of LRP1 in both contractile and synthetic SMCs. LRP1 inactivation decreased the proliferation and increased the migration capacity of contractile SMCs. Detailed characterization of the influence of LRP1 on extracellular matrix maintenance and cellular contraction is ongoing.Conclusions:We confirmed rs11172113 to regulate LRP1 expression in iPSCs derived contractile SMCs. Our results support LRP1 influence on SMCs phenotype as a causal factor in the genetic susceptibility to SCAD and related vascular diseases.

Published
2021
Full Text
View/download PDF

37. Genetic risk score for intracranial aneurysms to predict aneurysmal subarachnoid hemorrhage and identify associations with patient characteristics

Author

Bakker, Mark K., Kanning, Jos P., Abraham, Gad, Martinsen, Amy E., Winsvold, Bendik S., Zwart, John-Anker, Bourcier, Romain, Sawada, Tomonobu, Koido, Masaru, Kamatani, Yoichiro, Morel, Sandrine, Amouyel, Philippe, Debette, Stéphanie, Bijlenga, Philippe, Berrandou, Takiy, Ganesh, Santhi K., Bouatia-Naji, Nabila, Jones, Gregory, Bown, Matthew, Rinkel, Gabriël J.E., Veldink, Jan H., and Ruigrok, Ynte M.

Abstract

BackgroundRupture of an intracranial aneurysm (IA) causes aneurysmal subarachnoid hemorrhage (ASAH). There is no accurate prediction model for IA or ASAH in the general population. Recent discoveries in genetic risk for IA may allow improved risk prediction.MethodsWe constructed a genetic risk score including genetic association data for IA and 17 traits related to IA (a metaGRS) to predict ASAH incidence and IA presence. The metaGRS was trained in 1,161 IA cases and 407,392 controls in the UK Biobank and validated in combination with risk factors blood pressure, sex, and smoking in 828 IA cases and 68,568 controls from the Nordic HUNT study. We further assessed association between genetic risk load and patient characteristics in a cohort of 5,560 IA patients.ResultsThe hazard ratio for ASAH incidence was 1.34 (95% confidence interval = 1.20-1.51) per SD increase of metaGRS. Concordance index increased from 0.63 [0.59-0.67] to 0.65 [0.62-0.69] upon including the metaGRS on top of clinical risk factors. The odds ratio for prediction of IA presence was 1.09 [95% confidence interval: 1.01-1.18], but did not improve area under the curve. The metaGRS was statistically significantly associated with age at ASAH (β=-4.82×10−3 per year [-6.49×10−3 to -3.14×10−3], P=1.82×10−8), and location at the internal carotid artery (OR=0.92 [0.86 to 0.98], P=0.0041).ConclusionsThe metaGRS was predictive of ASAH incidence with modest added value over clinical risk factors. Genetic risk plays a role in clinical heterogeneity of IA. Additional studies are needed to identify the biological mechanisms underlying this heterogeneity.KEY MESSAGESWhat is already known on this topicRecent advanced in the understanding of genetic risk for IA opened and opportunity for risk prediction by combining genetic and conventional risk factors.What this study addsHere, we developed a genetic risk score based on genetic association information for IA and 17 related traits. This risk score improved prediction compared to a model including only conventional risk factors. Further, genetic risk was associated with age at ASAH and IA location.How this study might affect research, practice, or policyThis study emphasizes the importance of combining conventional and genetic risk factors in prediction of IA. It provides a metric to develop an accurate risk assessment method including conventional and genetic risk factors.

Full Text
View/download PDF

38. Genetic Risk Score for Intracranial Aneurysms: Prediction of Subarachnoid Hemorrhage and Role in Clinical Heterogeneity

Author

Mark K. Bakker, Jos P. Kanning, Gad Abraham, Amy E. Martinsen, Bendik S. Winsvold, John-Anker Zwart, Romain Bourcier, Tomonobu Sawada, Masaru Koido, Yoichiro Kamatani, Sandrine Morel, Philippe Amouyel, Stéphanie Debette, Philippe Bijlenga, Takiy Berrandou, Santhi K. Ganesh, Nabila Bouatia-Naji, Gregory Jones, Matthew Bown, Gabriel J.E. Rinkel, Jan H. Veldink, Ynte M. Ruigrok, Anne Hege Aamodt, Anne Heidi Skogholt, Ben M Brumpton, Cristen J Willer, Else C Sandset, Espen S Kristoffersen, Hanne Ellekjær, Ingrid Heuch, Jonas B Nielsen, Knut Hagen, Kristian Hveem, Lars G Fritsche, Laurent F Thomas, Linda M Pedersen, Maiken E Gabrielsen, Oddgeir L Holmen, Sigrid Børte, Wei Zhou, Shérine Abboud, Massimo Pandolfo, Vincent Thijs, Didier Leys, Marie Bodenant, Fabien Louillet, Emmanuel Touzé, Jean-Louis Mas, Yves Samson, Sara Leder, Anne Léger, Sandrine Deltour, Sophie Crozier, Isabelle Méresse, Sandrine Canaple, Olivier Godefroy, Maurice Giroud, Yannick Béjot, Pierre Decavel, Elizabeth Medeiros, Paola Montiel, Thierry Moulin, Fabrice Vuillier, Jean Dallongeville, Antti J Metso, Tiina Metso, Turgut Tatlisumak, Caspar Grond-Ginsbach, Christoph Lichy, Manja Kloss, Inge Werner, Marie-Luise Arnold, Michael Dos Santos, Armin Grau, Martin Dichgans, Constanze Thomas-Feles, Ralf Weber, Tobias Brandt, Alessandro Pezzini, Valeria De Giuli, Filomena Caria, Loris Poli, Alessandro Padovani, Anna Bersano, Silvia Lanfranconi, Simone Beretta, Carlo Ferrarese, Giacomo Giacolone, Stefano Paolucci, Philippe Lyrer, Stefan Engelter, Felix Fluri, Florian Hatz, Dominique Gisler, Leo Bonati, Henrik Gensicke, Margareth Amort, Hugh Markus, Jennifer Majersik, Bradford Worrall, Andrew Southerland, John Cole, Steven Kittner, Evangelos Evangelou, Helen R Warren, He Gao, Georgios Ntritsos, Niki Dimou, Tonu Esko, Reedik Mägi, Lili Milani, Peter Almgren, Thibaud Boutin, Jun Ding, Franco Giulianini, Elizabeth G Holliday, Anne U Jackson, Ruifang Li-Gao, Wei-Yu Lin, Jian’an Luan, Massimo Mangino, Christopher Oldmeadow, Bram Peter Prins, Yong Qian, Muralidharan Sargurupremraj, Nabi Shah, Praveen Surendran, Sébastien Thériault, Niek Verweij, Sara M Willems, Jing-Hua Zhao, John Connell, Renée de Mutsert, Alex SF Doney, Martin Farrall, Cristina Menni, Andrew D Morris, Raymond Noordam, Guillaume Paré, Neil R Poulter, Denis C Shields, Alice Stanton, Simon Thom, Gonçalo Abecasis, Najaf Amin, Dan E Arking, Kristin L Ayers, Caterina M Barbieri, Chiara Batini, Joshua C Bis, Tineka Blake, Murielle Bochud, Michael Boehnke, Eric Boerwinkle, Dorret I Boomsma, Erwin P Bottinger, Peter S Braund, Marco Brumat, Archie Campbell, Harry Campbell, Aravinda Chakravarti, John C Chambers, Ganesh Chauhan, Marina Ciullo, Massimiliano Cocca, Francis Collins, Heather J Cordell, Gail Davies, Martin H de Borst, Eco J de Geus, Ian J Deary, Joris Deelen, Fabiola Del Greco M, Cumhur Yusuf Demirkale, Marcus Dörr, Georg B Ehret, Roberto Elosua, Stefan Enroth, A Mesut Erzurumluoglu, Teresa Ferreira, Mattias Frånberg, Oscar H Franco, Ilaria Gandin, Paolo Gasparini, Vilmantas Giedraitis, Christian Gieger, Giorgia Girotto, Anuj Goel, Alan J Gow, Vilmundur Gudnason, Xiuqing Guo, Ulf Gyllensten, Anders Hamsten, Tamara B Harris, Sarah E Harris, Catharina A Hartman, Aki S Havulinna, Andrew A Hicks, Edith Hofer, Albert Hofman, Jouke-Jan Hottenga, Jennifer E Huffman, Shih-Jen Hwang, Erik Ingelsson, Alan James, Rick Jansen, Marjo-Riitta Jarvelin, Roby Joehanes, Åsa Johansson, Andrew D Johnson, Peter K Joshi, Pekka Jousilahti, J Wouter Jukema, Antti Jula, Mika Kähönen, Sekar Kathiresan, Bernard D Keavney, Kay-Tee Khaw, Paul Knekt, Joanne Knight, Ivana Kolcic, Jaspal S Kooner, Seppo Koskinen, Kati Kristiansson, Zoltan Kutalik, Maris Laan, Marty Larson, Lenore J Launer, Benjamin Lehne, Terho Lehtimäki, David CM Liewald, Li Lin, Lars Lind, Cecilia M Lindgren, YongMei Liu, Ruth JF Loos, Lorna M Lopez, Yingchang Lu, Leo-Pekka Lyytikäinen, Anubha Mahajan, Chrysovalanto Mamasoula, Jaume Marrugat, Jonathan Marten, Yuri Milaneschi, Anna Morgan, Andrew P Morris, Alanna C Morrison, Peter J Munson, Mike A Nalls, Priyanka Nandakumar, Christopher P Nelson, Teemu Niiranen, Ilja M Nolte, Teresa Nutile, Albertine J Oldehinkel, Ben A Oostra, Paul F O’Reilly, Elin Org, Sandosh Padmanabhan, Walter Palmas, Aarno Palotie, Alison Pattie, Brenda WJH Penninx, Markus Perola, Annette Peters, Ozren Polasek, Peter P Pramstaller, Quang Tri Nguyen, Olli T Raitakari, Rainer Rettig, Kenneth Rice, Paul M Ridker, Janina S Ried, Harriëtte Riese, Samuli Ripatti, Antonietta Robino, Lynda M Rose, Jerome I Rotter, Igor Rudan, Daniela Ruggiero, Yasaman Saba, Cinzia F Sala, Veikko Salomaa, Nilesh J Samani, Antti-Pekka Sarin, Reinhold Schmidt, Helena Schmidt, Nick Shrine, David Siscovick, Albert V Smith, Harold Snieder, Siim Sõber, Rossella Sorice, John M Starr, David J Stott, David P Strachan, Rona J Strawbridge, Johan Sundström, Morris A Swertz, Kent D Taylor, Alexander Teumer, Martin D Tobin, Maciej Tomaszewski, Daniela Toniolo, Michela Traglia, Stella Trompet, Jaakko Tuomilehto, Christophe Tzourio, André G Uitterlinden, Ahmad Vaez, Peter J van der Most, Cornelia M van Duijn, Germaine C Verwoert, Veronique Vitart, Uwe Völker, Peter Vollenweider, Dragana Vuckovic, Hugh Watkins, Sarah H Wild, Gonneke Willemsen, James F Wilson, Alan F Wright, Jie Yao, Tatijana Zemunik, Weihua Zhang, John R Attia, Adam S Butterworth, Daniel I Chasman, David Conen, Francesco Cucca, John Danesh, Caroline Hayward, Joanna MM Howson, Markku Laakso, Edward G Lakatta, Claudia Langenberg, Olle Melander, Dennis O Mook-Kanamori, Colin NA Palmer, Lorenz Risch, Robert A Scott, Rodney J Scott, Peter Sever, Tim D Spector, Pim van der Harst, Nicholas J Wareham, Eleftheria Zeggini, Daniel Levy, Patricia B Munroe, Christopher Newton-Cheh, Morris J Brown, Andres Metspalu, Bruce M. Psaty, Louise V Wain, Paul Elliott, Mark J Caulfield, Padhraig Gormley, Verneri Anttila, Priit Palta, Tune H Pers, Kai-How Farh, Ester Cuenca-Leon, Mikko Muona, Nicholas A Furlotte, Tobias Kurth, Andres Ingason, George McMahon, Lannie Ligthart, Gisela M Terwindt, Mikko Kallela, Tobias M Freilinger, Caroline Ran, Scott G Gordon, Anine H Stam, Stacy Steinberg, Guntram Borck, Markku Koiranen, Lydia Quaye, Hieab H H Adams, Juho Wedenoja, David A Hinds, Julie E Buring, Markus Schürks, Maria Gudlaug Hrafnsdottir, Hreinn Stefansson, Susan M Ring, Brenda W J H Penninx, Markus Färkkilä, Ville Artto, Mari Kaunisto, Salli Vepsäläinen, Rainer Malik, Andrew C Heath, Pamela A F Madden, Nicholas G Martin, Grant W Montgomery, Mitja I Kurki, Mart Kals, Kalle Pärn, Eija Hämäläinen, Hailiang Huang, Andrea E Byrnes, Lude Franke, Jie Huang, Evie Stergiakouli, Phil H Lee, Cynthia Sandor, Caleb Webber, Zameel Cader, Bertram Muller-Myhsok, Stefan Schreiber, Thomas Meitinger, Johan G Eriksson, Kauko Heikkilä, Elizabeth Loehrer, Andre G Uitterlinden, Lynn Cherkas, Audun Stubhaug, Christopher S Nielsen, Minna Männikkö, Evelin Mihailov, Hartmut Göbel, Ann-Louise Esserlind, Anne Francke Christensen, Thomas Folkmann Hansen, Thomas Werge, Jaakko Kaprio, Arpo J Aromaa, Olli Raitakari, M Arfan Ikram, Tim Spector, Marjo-Riitta Järvelin, Christian Kubisch, Michel D Ferrari, Andrea C Belin, Maija Wessman, Arn M J M van den Maagdenberg, George Davey Smith, Kari Stefansson, Nicholas Eriksson, Mark J Daly, Benjamin M Neale, Jes Olesen, Dale R Nyholt, Masato Akiyama, Varinder S. Alg, Joseph P. Broderick, Ben M. Brumpton, Jérôme Dauvillier, Hubert Desal, Christian Dina, Christoph M. Friedrich, Emília I. Gaál-Paavola, Jean-Christophe Gentric, Sven Hirsch, Isabel C. Hostettler, Henry Houlden, Juha E. Jääskeläinen, Marianne Bakke Johnsen, Liming Li, Kuang Lin, Antti Lindgren, Olivier Martin, Koichi Matsuda, Iona Y. Millwood, Olivier Naggara, Mika Niemelä, Joanna Pera, Richard Redon, Guy A. Rouleau, Marie Søfteland Sandvei, Sabine Schilling, Eimad Shotar, Agnieszka Slowik, Chikashi Terao, W. M. Monique Verschuren, Robin G. Walters, David J. Werring, Cristen J. Willer, Daniel Woo, Bradford B. Worrall, Sirui Zhou, Biological Psychology, Amsterdam Reproduction & Development, APH - Mental Health, APH - Methodology, AMS - Sports, AMS - Ageing & Vitality, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases, Systems Ecology, Sociology and Social Gerontology, Bakker, Mark K., Kanning, Jos P., Abraham, Gad, Martinsen, Amy E., Winsvold, Bendik S., Zwart, John-Anker, Bourcier, Romain, Sawada, Tomonobu, Koido, Masaru, Kamatani, Yoichiro, Morel, Sandrine, Amouyel, Philippe, Debette, Stéphanie, Bijlenga, Philippe, Berrandou, Takiy, Ganesh, Santhi K., Bouatia-Naji, Nabila, Jones, Gregory, Bown, Matthew, Rinkel, Gabriel J. E., Veldink, Jan H., Ruigrok, Ynte M., Girotto, G., All-In Stroke, Hunt, Group, Cadisp, Consortium for Blood Pressure, International, Headache Genetics Consortium, International, Stroke Genetics Consortium (ISGC) Intracranial Aneurysm Working Group, International, Utrecht University [Utrecht], Baker Heart and Diabetes Institute (AUSTRALIA), University of Melbourne, University of Oslo (UiO), Norwegian University of Science and Technology (NTNU), Oslo University Hospital [Oslo], Centre hospitalier universitaire de Nantes (CHU Nantes), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), The University of Tokyo (UTokyo), RIKEN Center for Integrative Medical Sciences [Yokohama] (RIKEN IMS), RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), Hôpital Universitaire de Genève = University Hospitals of Geneva (HUG), Université de Genève = University of Geneva (UNIGE), Excellence Laboratory LabEx DISTALZ, Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), University of Michigan Medical School [Ann Arbor], University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, University of Otago [Dunedin, Nouvelle-Zélande], University of Leicester, Laboratoire de Neurosciences Fonctionnelles et Pathologies - UR UPJV 4559 (LNFP), Université de Picardie Jules Verne (UPJV), CHU Amiens-Picardie, HUNT All-In Stroke, CADISP group, International Consortium for Blood Pressure, International Headache Genetics Consortium, International Stroke Genetics Consortium (ISGC) Intracranial Aneurysm Working Group: Anne Hege Aamodt, Anne Heidi Skogholt, Ben M Brumpton, Cristen J Willer, Else C Sandset, Espen S Kristoffersen, Hanne Ellekjær, Ingrid Heuch, Jonas B Nielsen, Knut Hagen, Kristian Hveem, Lars G Fritsche, Laurent F Thomas, Linda M Pedersen, Maiken E Gabrielsen, Oddgeir L Holmen, Sigrid Børte, Wei Zhou, Shérine Abboud, Massimo Pandolfo, Vincent Thijs, Didier Leys, Marie Bodenant, Fabien Louillet, Emmanuel Touzé, Jean-Louis Mas, Yves Samson, Sara Leder, Anne Léger, Sandrine Deltour, Sophie Crozier, Isabelle Méresse, Sandrine Canaple, Olivier Godefroy, Maurice Giroud, Yannick Béjot, Pierre Decavel, Elizabeth Medeiros, Paola Montiel, Thierry Moulin, Fabrice Vuillier, Jean Dallongeville, Antti J Metso, Tiina Metso, Turgut Tatlisumak, Caspar Grond-Ginsbach, Christoph Lichy, Manja Kloss, Inge Werner, Marie-Luise Arnold, Michael Dos Santos, Armin Grau, Martin Dichgans, Constanze Thomas-Feles, Ralf Weber, Tobias Brandt, Alessandro Pezzini, Valeria De Giuli, Filomena Caria, Loris Poli, Alessandro Padovani, Anna Bersano, Silvia Lanfranconi, Simone Beretta, Carlo Ferrarese, Giacomo Giacolone, Stefano Paolucci, Philippe Lyrer, Stefan Engelter, Felix Fluri, Florian Hatz, Dominique Gisler, Leo Bonati, Henrik Gensicke, Margareth Amort, Hugh Markus, Jennifer Majersik, Bradford Worrall, Andrew Southerland, John Cole, Steven Kittner, Evangelos Evangelou, Helen R Warren, He Gao, Georgios Ntritsos, Niki Dimou, Tonu Esko, Reedik Mägi, Lili Milani, Peter Almgren, Thibaud Boutin, Jun Ding, Franco Giulianini, Elizabeth G Holliday, Anne U Jackson, Ruifang Li-Gao, Wei-Yu Lin, Jian'an Luan, Massimo Mangino, Christopher Oldmeadow, Bram Peter Prins, Yong Qian, Muralidharan Sargurupremraj, Nabi Shah, Praveen Surendran, Sébastien Thériault, Niek Verweij, Sara M Willems, Jing-Hua Zhao, John Connell, Renée de Mutsert, Alex Sf Doney, Martin Farrall, Cristina Menni, Andrew D Morris, Raymond Noordam, Guillaume Paré, Neil R Poulter, Denis C Shields, Alice Stanton, Simon Thom, Gonçalo Abecasis, Najaf Amin, Dan E Arking, Kristin L Ayers, Caterina M Barbieri, Chiara Batini, Joshua C Bis, Tineka Blake, Murielle Bochud, Michael Boehnke, Eric Boerwinkle, Dorret I Boomsma, Erwin P Bottinger, Peter S Braund, Marco Brumat, Archie Campbell, Harry Campbell, Aravinda Chakravarti, John C Chambers, Ganesh Chauhan, Marina Ciullo, Massimiliano Cocca, Francis Collins, Heather J Cordell, Gail Davies, Martin H de Borst, Eco J de Geus, Ian J Deary, Joris Deelen, Fabiola Del Greco M, Cumhur Yusuf Demirkale, Marcus Dörr, Georg B Ehret, Roberto Elosua, Stefan Enroth, A Mesut Erzurumluoglu, Teresa Ferreira, Mattias Frånberg, Oscar H Franco, Ilaria Gandin, Paolo Gasparini, Vilmantas Giedraitis, Christian Gieger, Giorgia Girotto, Anuj Goel, Alan J Gow, Vilmundur Gudnason, Xiuqing Guo, Ulf Gyllensten, Anders Hamsten, Tamara B Harris, Sarah E Harris, Catharina A Hartman, Aki S Havulinna, Andrew A Hicks, Edith Hofer, Albert Hofman, Jouke-Jan Hottenga, Jennifer E Huffman, Shih-Jen Hwang, Erik Ingelsson, Alan James, Rick Jansen, Marjo-Riitta Jarvelin, Roby Joehanes, Åsa Johansson, Andrew D Johnson, Peter K Joshi, Pekka Jousilahti, J Wouter Jukema, Antti Jula, Mika Kähönen, Sekar Kathiresan, Bernard D Keavney, Kay-Tee Khaw, Paul Knekt, Joanne Knight, Ivana Kolcic, Jaspal S Kooner, Seppo Koskinen, Kati Kristiansson, Zoltan Kutalik, Maris Laan, Marty Larson, Lenore J Launer, Benjamin Lehne, Terho Lehtimäki, David Cm Liewald, Li Lin, Lars Lind, Cecilia M Lindgren, YongMei Liu, Ruth Jf Loos, Lorna M Lopez, Yingchang Lu, Leo-Pekka Lyytikäinen, Anubha Mahajan, Chrysovalanto Mamasoula, Jaume Marrugat, Jonathan Marten, Yuri Milaneschi, Anna Morgan, Andrew P Morris, Alanna C Morrison, Peter J Munson, Mike A Nalls, Priyanka Nandakumar, Christopher P Nelson, Teemu Niiranen, Ilja M Nolte, Teresa Nutile, Albertine J Oldehinkel, Ben A Oostra, Paul F O'Reilly, Elin Org, Sandosh Padmanabhan, Walter Palmas, Aarno Palotie, Alison Pattie, Brenda Wjh Penninx, Markus Perola, Annette Peters, Ozren Polasek, Peter P Pramstaller, Quang Tri Nguyen, Olli T Raitakari, Rainer Rettig, Kenneth Rice, Paul M Ridker, Janina S Ried, Harriëtte Riese, Samuli Ripatti, Antonietta Robino, Lynda M Rose, Jerome I Rotter, Igor Rudan, Daniela Ruggiero, Yasaman Saba, Cinzia F Sala, Veikko Salomaa, Nilesh J Samani, Antti-Pekka Sarin, Reinhold Schmidt, Helena Schmidt, Nick Shrine, David Siscovick, Albert V Smith, Harold Snieder, Siim Sõber, Rossella Sorice, John M Starr, David J Stott, David P Strachan, Rona J Strawbridge, Johan Sundström, Morris A Swertz, Kent D Taylor, Alexander Teumer, Martin D Tobin, Maciej Tomaszewski, Daniela Toniolo, Michela Traglia, Stella Trompet, Jaakko Tuomilehto, Christophe Tzourio, André G Uitterlinden, Ahmad Vaez, Peter J van der Most, Cornelia M van Duijn, Germaine C Verwoert, Veronique Vitart, Uwe Völker, Peter Vollenweider, Dragana Vuckovic, Hugh Watkins, Sarah H Wild, Gonneke Willemsen, James F Wilson, Alan F Wright, Jie Yao, Tatijana Zemunik, Weihua Zhang, John R Attia, Adam S Butterworth, Daniel I Chasman, David Conen, Francesco Cucca, John Danesh, Caroline Hayward, Joanna Mm Howson, Markku Laakso, Edward G Lakatta, Claudia Langenberg, Olle Melander, Dennis O Mook-Kanamori, Colin Na Palmer, Lorenz Risch, Robert A Scott, Rodney J Scott, Peter Sever, Tim D Spector, Pim van der Harst, Nicholas J Wareham, Eleftheria Zeggini, Daniel Levy, Patricia B Munroe, Christopher Newton-Cheh, Morris J Brown, Andres Metspalu, Bruce M Psaty, Louise V Wain, Paul Elliott, Mark J Caulfield, Padhraig Gormley, Verneri Anttila, Priit Palta, Tonu Esko, Tune H Pers, Kai-How Farh, Ester Cuenca-Leon, Mikko Muona, Nicholas A Furlotte, Tobias Kurth, Andres Ingason, George McMahon, Lannie Ligthart, Gisela M Terwindt, Mikko Kallela, Tobias M Freilinger, Caroline Ran, Scott G Gordon, Anine H Stam, Stacy Steinberg, Guntram Borck, Markku Koiranen, Lydia Quaye, Hieab H H Adams, Terho Lehtimäki, Antti-Pekka Sarin, Juho Wedenoja, David A Hinds, Julie E Buring, Markus Schürks, Paul M Ridker, Maria Gudlaug Hrafnsdottir, Hreinn Stefansson, Susan M Ring, Jouke-Jan Hottenga, Brenda W J H Penninx, Markus Färkkilä, Ville Artto, Mari Kaunisto, Salli Vepsäläinen, Rainer Malik, Andrew C Heath, Pamela A F Madden, Nicholas G Martin, Grant W Montgomery, Mitja I Kurki, Mart Kals, Reedik Mägi, Kalle Pärn, Eija Hämäläinen, Hailiang Huang, Andrea E Byrnes, Lude Franke, Jie Huang, Evie Stergiakouli, Phil H Lee, Cynthia Sandor, Caleb Webber, Zameel Cader, Bertram Muller-Myhsok, Stefan Schreiber, Thomas Meitinger, Johan G Eriksson, Veikko Salomaa, Kauko Heikkilä, Elizabeth Loehrer, Andre G Uitterlinden, Albert Hofman, Cornelia M van Duijn, Lynn Cherkas, Linda M Pedersen, Audun Stubhaug, Christopher S Nielsen, Minna Männikkö, Evelin Mihailov, Lili Milani, Hartmut Göbel, Ann-Louise Esserlind, Anne Francke Christensen, Thomas Folkmann Hansen, Thomas Werge, Jaakko Kaprio, Arpo J Aromaa, Olli Raitakari, M Arfan Ikram, Tim Spector, Marjo-Riitta Järvelin, Andres Metspalu, Christian Kubisch, David P Strachan, Michel D Ferrari, Andrea C Belin, Martin Dichgans, Maija Wessman, Arn M J M van den Maagdenberg, Dorret I Boomsma, George Davey Smith, Kari Stefansson, Nicholas Eriksson, Mark J Daly, Benjamin M Neale, Jes Olesen, Daniel I Chasman, Dale R Nyholt, Aarno Palotie, Masato Akiyama, Varinder S Alg, Sigrid Børte, Joseph P Broderick, Ben M Brumpton, Jérôme Dauvillier, Hubert Desal, Christian Dina, Christoph M Friedrich, Emília I Gaál-Paavola, Jean-Christophe Gentric, Sven Hirsch, Isabel C Hostettler, Henry Houlden, Kristian Hveem, Juha E Jääskeläinen, Marianne Bakke Johnsen, Liming Li, Kuang Lin, Antti Lindgren, Olivier Martin, Koichi Matsuda, Iona Y Millwood, Olivier Naggara, Mika Niemelä, Joanna Pera, Richard Redon, Guy A Rouleau, Marie Søfteland Sandvei, Sabine Schilling, Eimad Shotar, Agnieszka Slowik, Chikashi Terao, W M Monique Verschuren, Robin G Walters, David J Werring, Cristen J Willer, Daniel Woo, Bradford B Worrall, Sirui Zhou, Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, and Admin, Oskar

Subjects
Advanced and Specialized Nursing, Incidence, risk assessment, Smoking/epidemiology, intracranial aneurysm, genetic heterogeneity, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Risk Factors, Intracranial Aneurysm/epidemiology, Humans, Subarachnoid Hemorrhage/epidemiology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, genetics, Neurology (clinical), aneurysmal subarachnoid hemorrhage, genetic, Cardiology and Cardiovascular Medicine
Abstract

Background: Recently, common genetic risk factors for intracranial aneurysm (IA) and aneurysmal subarachnoid hemorrhage (ASAH) were found to explain a large amount of disease heritability and therefore have potential to be used for genetic risk prediction. We constructed a genetic risk score to (1) predict ASAH incidence and IA presence (combined set of unruptured IA and ASAH) and (2) assess its association with patient characteristics. Methods: A genetic risk score incorporating genetic association data for IA and 17 traits related to IA (so-called metaGRS) was created using 1161 IA cases and 407 392 controls from the UK Biobank population study. The metaGRS was validated in combination with risk factors blood pressure, sex, and smoking in 828 IA cases and 68 568 controls from the Nordic HUNT population study. Furthermore, we assessed association between the metaGRS and patient characteristics in a cohort of 5560 IA patients. Results: Per SD increase of metaGRS, the hazard ratio for ASAH incidence was 1.34 (95% CI, 1.20–1.51) and the odds ratio for IA presence 1.09 (95% CI, 1.01–1.18). Upon including the metaGRS on top of clinical risk factors, the concordance index to predict ASAH hazard increased from 0.63 (95% CI, 0.59–0.67) to 0.65 (95% CI, 0.62–0.69), while prediction of IA presence did not improve. The metaGRS was statistically significantly associated with age at ASAH (β=−4.82×10 −3 per year [95% CI, −6.49×10 −3 to −3.14×10 −3 ]; P =1.82×10 −8 ), and location of IA at the internal carotid artery (odds ratio=0.92 [95% CI, 0.86–0.98]; P =0.0041). Conclusions: The metaGRS was predictive of ASAH incidence, although with limited added value over clinical risk factors. The metaGRS was not predictive of IA presence. Therefore, we do not recommend using this metaGRS in daily clinical care. Genetic risk does partly explain the clinical heterogeneity of IA warranting prioritization of clinical heterogeneity in future genetic prediction studies of IA and ASAH.

Published
2023
Full Text
View/download PDF

39. Variants in the Kallikrein Gene Family and Hypermobile Ehlers-Danlos Syndrome.

Author

Gensemer C, Beck T, Guo L, Petrucci T, Morningstar J, Kornblau I, Byerly K, Biggs R, Weintraub A, Moore K, Koren N, Daylor V, Hastings C, Oberlies E, Zientara ER, Devey E, Dooley S, Stayer K, Fenner R, Singleton K, Luzbetak S, Bear D, Byrd R, Weninger J, Bistran E, Beeson G, Kerns J, Griggs M, Griggs C, Osterhaus M, Fleck E, Schnaudigel J, Butler S, Severance S, Kendall W, Delaney JR, Judge DP, Chen P, Yao H, Guz J, Awgulewitsch A, Kautz SA, Mukherjee R, Price R, Henderson F Sr, Shapiro S, Francomano CA, Kovacic JC, Lavallee M, Patel S, Berrandou TE, Slaugenhaupt SA, Milan D, Kontorovich AR, Bouatia-Naji N, and Norris RA

Abstract

Hypermobile Ehlers-Danlos syndrome (hEDS) is a common heritable connective tissue disorder that lacks a known genetic etiology. To identify genetic contributions to hEDS, whole exome sequencing was performed on families and a cohort of sporadic hEDS patients. A missense variant in Kallikrein-15 (KLK15 p. Gly226Asp), segregated with disease in two families and genetic burden analyses of 197 sporadic hEDS patients revealed enrichment of variants within the Kallikrein gene family. To validate pathogenicity, the variant identified in familial studies was used to generate knock-in mice. Consistent with our clinical cohort, Klk15 G224D/+ mice displayed structural and functional connective tissue defects within multiple organ systems. These findings support Kallikrein gene variants in the pathogenesis of hEDS and represent an important step towards earlier diagnosis and better clinical outcomes.

Published
2024
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results