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

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Bakker, M. K. (author)

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

Article/chapterEnglish2020

Publisher, publication year, extent ...

2020-11-16
Springer Science and Business Media LLC,2020

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LIBRIS-ID:oai:gup.ub.gu.se/300001
https://gup.ub.gu.se/publication/300001URI
https://doi.org/10.1038/s41588-020-00725-7DOI

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Language:English

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SwePubSwePub

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Subject category:ref swepub-contenttype
Subject category:art swepub-publicationtype

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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. Cross-ancestry genome-wide association analyses in individuals of European and East Asian ancestry identify 11 new risk loci for intracranial aneurysms and highlight a polygenic architecture explaining a substantial fraction of disease heritability.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine hsv//eng
ld score regression
subarachnoid hemorrhage
gwas
metaanalysis
sex
heritability
variants
smoking
patient
growth
Genetics & Heredity

Added entries (persons, corporate bodies, meetings, titles ...)

van der Spek, R. A. A. (author)
van Rheenen, W. (author)
Morel, S. (author)
Bourcier, R. (author)
Hostettler, I. C. (author)
Alg, V. S. (author)
van Eijk, K. R. (author)
Koido, M. (author)
Akiyama, M. (author)
Terao, C. (author)
Matsuda, K. (author)
Walters, R. G. (author)
Lin, K. (author)
Li, L. M. (author)
Millwood, I. Y. (author)
Chen, Z. M. (author)
Rouleau, G. A. (author)
Zhou, S. R. (author)
Rannikmae, K. (author)
Sudlow, C. L. M. (author)
Houlden, H. (author)
van den Berg, L. H. (author)
Dina, C. (author)
Naggara, O. (author)
Gentric, J. C. (author)
Shotar, E. (author)
Eugene, F. (author)
Desal, H. (author)
Winsvold, B. S. (author)
Borte, S. (author)
Johnsen, M. B. (author)
Brumpton, B. (author)
Sandvei, M. S. (author)
Willer, C. J. (author)
Hveem, K. (author)
Zwart, J. A. (author)
Verschuren, W. M. M. (author)
Friedrich, C. M. (author)
Hirsch, S. (author)
Schilling, S. (author)
Dauvillier, J. M. (author)
Martin, O. (author)
Winsvold, B. S. (author)
Winsvold, B. S. (author)
Borte, S. (author)
Johnsen, M. B. (author)
Brumpton, B. M. (author)
Sandvei, M. S. (author)
Willer, C. J. (author)
Hveem, K. (author)
Zwart, J. A. (author)
Bian, Z. (author)
Chen, J. S. (author)
Chen, Y. P. (author)
Chen, Z. M. (author)
Clarke, R. (author)
Collins, R. (author)
Guo, Y. (author)
Han, X. (author)
Hill, M. (author)
Li, L. M. (author)
Lin, K. (author)
Liu, D. P. (author)
Lv, J. (author)
Millwood, I. (author)
Peto, R. (author)
Sansome, S. (author)
Walters, R. (author)
Yang, X. M. (author)
Yu, C. Q. (author)
Koido, M. (author)
Koido, M. (author)
Akiyama, M. (author)
Terao, C. (author)
Matsuda, K. (author)
Kamatani, Y. (author)
Desal, H. (author)
Desal, H. (author)
Bourcier, R. (author)
Redon, R. (author)
Dina, C. (author)
Naggara, O. (author)
Eugene, F. (author)
Gentric, J. C. (author)
Shotar, E. (author)
Sargurupremraj, Muralidharan (author)
Tatlisumak, TurgutGothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap,Institute of Neuroscience and Physiology, Department of Clinical Neuroscience(Swepub:gu)xtatlt (author)
Debette, S. (author)
Werring, D. J. (author)
Houlden, H. (author)
Alg, V. S. (author)
Hostettler, I. C. (author)
Bonner, S. (author)
Walsh, D. (author)
Bulters, D. (author)
Kitchen, N. (author)
Brown, M. (author)
Grieve, J. (author)
Bourcier, R. (author)
Walters, R. G. (author)
Malik, R. (author)
Dichgans, M. (author)
Sargurupremraj, M. (author)
Tatlisumak, T. (author)
Debette, S. (author)
Rinkel, G. J. E. (author)
Worrall, B. B. (author)
Pera, J. (author)
Slowik, A. (author)
Broderick, J. P. (author)
Werring, D. J. (author)
Woo, D. (author)
Bijlenga, P. (author)
Kamatani, Y. (author)
Ruigrok, Y. M. (author)
Jones, G. T. (author)
Bown, M. J. (author)
Ko, N. E. U. (author)
Kim, H. (author)
Coleman, J. R. I. (author)
Breen, G. (author)
Zaroff, J. G. (author)
Klijn, C. J. M. (author)
Malik, R. (author)
Dichgans, M. (author)
Sargurupremraj, M. (author)
Tatlisumak, T. (author)
Amouyel, P. (author)
Debette, S. (author)
Rinkel, G. J. E. (author)
Worrall, B. B. (author)
Pera, J. (author)
Slowik, A. (author)
Gaal-Paavola, E. I. (author)
Niemela, M. (author)
Jaaskelainen, J. E. (author)
Zu Fraunberg, M. V. (author)
Lindgren, A. (author)
Broderick, J. P. (author)
Werring, D. J. (author)
Woo, D. (author)
Redon, R. (author)
Bijlenga, P. (author)
Kamatani, Y. (author)
Veldink, J. H. (author)
Ruigrok, Y. M. (author)
Göteborgs universitetInstitutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap (creator_code:org_t)

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In:Nature Genetics: Springer Science and Business Media LLC52:12, s. 1303-13131061-40361546-1718

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By the author/editor: Bakker, M. K.; van der Spek, R. ...; van Rheenen, W.; Morel, S.; Bourcier, R.; Hostettler, I. C ...; show more...; Alg, V. S.; van Eijk, K. R.; Koido, M.; Akiyama, M.; Terao, C.; Matsuda, K.; Walters, R. G.; Lin, K.; Li, L. M.; Millwood, I. Y.; Chen, Z. M.; Rouleau, G. A.; Zhou, S. R.; Rannikmae, K.; Sudlow, C. L. M.; Houlden, H.; van den Berg, L. ...; Dina, C.; Naggara, O.; Gentric, J. C.; Shotar, E.; Eugene, F.; Desal, H.; Winsvold, B. S.; Borte, S.; Johnsen, M. B.; Brumpton, B.; Sandvei, M. S.; Willer, C. J.; Hveem, K.; Zwart, J. A.; Verschuren, W. M ...; Friedrich, C. M.; Hirsch, S.; Schilling, S.; Dauvillier, J. M ...; Martin, O.; Brumpton, B. M.; Bian, Z.; Chen, J. S.; Chen, Y. P.; Clarke, R.; Collins, R.; Guo, Y.; Han, X.; Hill, M.; Liu, D. P.; Lv, J.; Millwood, I.; Peto, R.; Sansome, S.; Walters, R.; Yang, X. M.; Yu, C. Q.; Kamatani, Y.; Redon, R.; Sargurupremraj, ...; Tatlisumak, Turg ...; Debette, S.; Werring, D. J.; Bonner, S.; Walsh, D.; Bulters, D.; Kitchen, N.; Brown, M.; Grieve, J.; Malik, R.; Dichgans, M.; Sargurupremraj, ...; Tatlisumak, T.; Rinkel, G. J. E.; Worrall, B. B.; Pera, J.; Slowik, A.; Broderick, J. P.; Woo, D.; Bijlenga, P.; Ruigrok, Y. M.; Jones, G. T.; Bown, M. J.; Ko, N. E. U.; Kim, H.; Coleman, J. R. I ...; Breen, G.; Zaroff, J. G.; Klijn, C. J. M.; Amouyel, P.; Gaal-Paavola, E. ...; Niemela, M.; Jaaskelainen, J. ...; Zu Fraunberg, M. ...; Lindgren, A.; Veldink, J. H.; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...

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