Genome-wide association study of intracranial aneurysms identifies 17 risk loci and genetic overlap with clinical risk factors

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; Jones, Gregory T.; Bown, Matthew J.; Ko, Nerissa U.; Kim, Helen; Coleman, Jonathan R. I.; Breen, Gerome; Zaroff, Jonathan G.; Klijn, Catharina J. M.; Malik, Rainer; Dichgans, Martin; Sargurupremraj, Muralidharan; Tatlisumak, Turgut; Amouyel, Philippe; Debette, Stéphanie; Rinkel, Gabriel J. E.; Worrall, Bradford B.; Pera, Joanna; Slowik, Agnieszka; Gaál-Paavola, Emília I.; Niemelä, Mika; Jääskeläinen, Juha E.; von Und Zu Fraunberg, Mikael; Lindgren, Antti; Broderick, Joseph P.; Werring, David J.; Woo, Daniel; Redon, Richard; Bijlenga, Philippe; Kamatani, Yoichiro; Veldink, Jan H.; Ruigrok, Ynte M.

doi:10.1038/s41588-020-00725-7

Publication type:	Article in scientific journal
Type of review:	Peer review (publication)
Title:	Genome-wide association study of intracranial aneurysms identifies 17 risk loci and genetic overlap with clinical risk factors
Authors:	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 Jones, Gregory T. Bown, Matthew J. Ko, Nerissa U. Kim, Helen Coleman, Jonathan R. I. Breen, Gerome Zaroff, Jonathan G. Klijn, Catharina J. M. Malik, Rainer Dichgans, Martin Sargurupremraj, Muralidharan Tatlisumak, Turgut Amouyel, Philippe Debette, Stéphanie Rinkel, Gabriel J. E. Worrall, Bradford B. Pera, Joanna Slowik, Agnieszka Gaál-Paavola, Emília I. Niemelä, Mika Jääskeläinen, Juha E. von Und Zu Fraunberg, Mikael Lindgren, Antti Broderick, Joseph P. Werring, David J. Woo, Daniel Redon, Richard Bijlenga, Philippe Kamatani, Yoichiro Veldink, Jan H. Ruigrok, Ynte M.
et. al:	No
DOI:	10.1038/s41588-020-00725-7
Published in:	Nature Genetics
Volume(Issue):	52
Issue:	12
Page(s):	1303
Pages to:	1313
Issue Date:	16-Nov-2020
Publisher / Ed. Institution:	Nature Publishing Group
ISSN:	1061-4036 1546-1718
Language:	English
Subjects:	Cerebrovascular disorder; Genome-wide association study; Stroke; Intracranial aneurysm; Genetic risk factor
Subject (DDC):	572: Biochemistry 616: Internal medicine and diseases
Abstract:	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.
Further description:	An author correction to this article published in December 2020 is available at https://doi.org/10.1038/s41588-020-00760-4.
URI:	https://europepmc.org/article/PMC/7116530 https://digitalcollection.zhaw.ch/handle/11475/21534
Fulltext version:	Published version
License (according to publishing contract):	Licence according to publishing contract
Departement:	Life Sciences and Facility Management
Organisational Unit:	Institute of Computational Life Sciences (ICLS)
Published as part of the ZHAW project:	AneuX
Appears in collections:	Publikationen Life Sciences und Facility Management

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Bakker, M. K., van der Spek, R. A. A., van Rheenen, W., Morel, S., Bourcier, R., Hostettler, I. C., Alg, V. S., van Eijk, K. R., Koido, M., Akiyama, M., Terao, C., Matsuda, K., Walters, R. G., Lin, K., Li, L., Millwood, I. Y., Chen, Z., Rouleau, G. A., Zhou, S., et al. (2020). Genome-wide association study of intracranial aneurysms identifies 17 risk loci and genetic overlap with clinical risk factors. Nature Genetics, 52(12), 1303–1313. https://doi.org/10.1038/s41588-020-00725-7

Bakker, M.K. et al. (2020) ‘Genome-wide association study of intracranial aneurysms identifies 17 risk loci and genetic overlap with clinical risk factors’, Nature Genetics, 52(12), pp. 1303–1313. Available at: https://doi.org/10.1038/s41588-020-00725-7.

M. K. Bakker et al., “Genome-wide association study of intracranial aneurysms identifies 17 risk loci and genetic overlap with clinical risk factors,” Nature Genetics, vol. 52, no. 12, pp. 1303–1313, Nov. 2020, doi: 10.1038/s41588-020-00725-7.

BAKKER, Mark K., Rick A. A. VAN DER SPEK, Wouter VAN RHEENEN, Sandrine MOREL, Romain BOURCIER, Isabel C. HOSTETTLER, Varinder S. ALG, Kristel R. VAN EIJK, Masaru KOIDO, Masato AKIYAMA, Chikashi TERAO, Koichi MATSUDA, Robin G. WALTERS, Kuang LIN, Liming LI, Iona Y. MILLWOOD, Zhengming CHEN, Guy A. ROULEAU, Sirui ZHOU, Kristiina RANNIKMÄE, Cathie L. M. SUDLOW, Henry HOULDEN, Leonard H. VAN DEN BERG, Christian DINA, Olivier NAGGARA, Jean-Christophe GENTRIC, Eimad SHOTAR, François EUGÈNE, Hubert DESAL, Bendik S. WINSVOLD, Sigrid BØRTE, Marianne Bakke JOHNSEN, Ben M. BRUMPTON, Marie Søfteland SANDVEI, Cristen J. WILLER, Kristian HVEEM, John-Anker ZWART, W. M. Monique VERSCHUREN, Christoph M. FRIEDRICH, Sven HIRSCH, Sabine SCHILLING, Jérôme DAUVILLIER, Olivier MARTIN, Gregory T. JONES, Matthew J. BOWN, Nerissa U. KO, Helen KIM, Jonathan R. I. COLEMAN, Gerome BREEN, Jonathan G. ZAROFF, Catharina J. M. KLIJN, Rainer MALIK, Martin DICHGANS, Muralidharan SARGURUPREMRAJ, Turgut TATLISUMAK, Philippe AMOUYEL, Stéphanie DEBETTE, Gabriel J. E. RINKEL, Bradford B. WORRALL, Joanna PERA, Agnieszka SLOWIK, Emília I. GAÁL-PAAVOLA, Mika NIEMELÄ, Juha E. JÄÄSKELÄINEN, Mikael VON UND ZU FRAUNBERG, Antti LINDGREN, Joseph P. BRODERICK, David J. WERRING, Daniel WOO, Richard REDON, Philippe BIJLENGA, Yoichiro KAMATANI, Jan H. VELDINK und Ynte M. RUIGROK, 2020. Genome-wide association study of intracranial aneurysms identifies 17 risk loci and genetic overlap with clinical risk factors. Nature Genetics [online]. 16 November 2020. Bd. 52, Nr. 12, S. 1303–1313. DOI 10.1038/s41588-020-00725-7. Verfügbar unter: https://europepmc.org/article/PMC/7116530

Bakker, Mark K., Rick A. A. van der Spek, Wouter van Rheenen, Sandrine Morel, Romain Bourcier, Isabel C. Hostettler, Varinder S. Alg, et al. 2020. “Genome-Wide Association Study of Intracranial Aneurysms Identifies 17 Risk Loci and Genetic Overlap with Clinical Risk Factors.” Nature Genetics 52 (12): 1303–13. https://doi.org/10.1038/s41588-020-00725-7.

Bakker, Mark K., et al. “Genome-Wide Association Study of Intracranial Aneurysms Identifies 17 Risk Loci and Genetic Overlap with Clinical Risk Factors.” Nature Genetics, vol. 52, no. 12, Nov. 2020, pp. 1303–13, https://doi.org/10.1038/s41588-020-00725-7.