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000154282 0247_ $$2doi$$a10.1038/s41588-020-00725-7
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000154282 037__ $$aDZNE-2021-00136
000154282 041__ $$aEnglish
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000154282 1001_ $$00000-0002-7887-9014$$aBakker, Mark K$$b0
000154282 245__ $$aGenome-wide association study of intracranial aneurysms identifies 17 risk loci and genetic overlap with clinical risk factors.
000154282 260__ $$aLondon$$bMacmillan Publishers Limited, part of Springer Nature$$c2020
000154282 3367_ $$2DRIVER$$aarticle
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000154282 520__ $$aRupture 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.
000154282 536__ $$0G:(DE-HGF)POF3-344$$a344 - Clinical and Health Care Research (POF3-344)$$cPOF3-344$$fPOF III$$x0
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000154282 650_2 $$2MeSH$$aAsian People: genetics
000154282 650_2 $$2MeSH$$aAsian Continental Ancestry Group: genetics
000154282 650_2 $$2MeSH$$aBlood Pressure: genetics
000154282 650_2 $$2MeSH$$aCase-Control Studies
000154282 650_2 $$2MeSH$$aEndothelial Cells: pathology
000154282 650_2 $$2MeSH$$aEuropean Continental Ancestry Group: genetics
000154282 650_2 $$2MeSH$$aGenetic Predisposition to Disease: genetics
000154282 650_2 $$2MeSH$$aGenome-Wide Association Study
000154282 650_2 $$2MeSH$$aHumans
000154282 650_2 $$2MeSH$$aHypertension: genetics
000154282 650_2 $$2MeSH$$aHypertension: physiopathology
000154282 650_2 $$2MeSH$$aIntracranial Aneurysm: genetics
000154282 650_2 $$2MeSH$$aIntracranial Aneurysm: pathology
000154282 650_2 $$2MeSH$$aPolymorphism, Single Nucleotide: genetics
000154282 650_2 $$2MeSH$$aRisk Factors
000154282 650_2 $$2MeSH$$aSmoking: adverse effects
000154282 650_2 $$2MeSH$$aSmoking: genetics
000154282 650_2 $$2MeSH$$aSubarachnoid Hemorrhage: genetics
000154282 650_2 $$2MeSH$$aSubarachnoid Hemorrhage: pathology
000154282 650_2 $$2MeSH$$aWhite People: genetics
000154282 7001_ $$avan der Spek, Rick A A$$b1
000154282 7001_ $$00000-0002-5860-1533$$avan Rheenen, Wouter$$b2
000154282 7001_ $$00000-0003-1538-3553$$aMorel, Sandrine$$b3
000154282 7001_ $$aBourcier, Romain$$b4
000154282 7001_ $$00000-0002-9004-2540$$aHostettler, Isabel C$$b5
000154282 7001_ $$aAlg, Varinder S$$b6
000154282 7001_ $$avan Eijk, Kristel R$$b7
000154282 7001_ $$00000-0002-0348-0666$$aKoido, Masaru$$b8
000154282 7001_ $$aAkiyama, Masato$$b9
000154282 7001_ $$00000-0002-6452-4095$$aTerao, Chikashi$$b10
000154282 7001_ $$00000-0001-7292-2686$$aMatsuda, Koichi$$b11
000154282 7001_ $$00000-0002-9179-0321$$aWalters, Robin G$$b12
000154282 7001_ $$aLin, Kuang$$b13
000154282 7001_ $$aLi, Liming$$b14
000154282 7001_ $$aMillwood, Iona Y$$b15
000154282 7001_ $$00000-0001-6423-105X$$aChen, Zhengming$$b16
000154282 7001_ $$00000-0001-8403-1418$$aRouleau, Guy A$$b17
000154282 7001_ $$aZhou, Sirui$$b18
000154282 7001_ $$00000-0002-2384-7568$$aRannikmäe, Kristiina$$b19
000154282 7001_ $$aSudlow, Cathie L M$$b20
000154282 7001_ $$00000-0002-2866-7777$$aHoulden, Henry$$b21
000154282 7001_ $$avan den Berg, Leonard H$$b22
000154282 7001_ $$00000-0002-7722-7348$$aDina, Christian$$b23
000154282 7001_ $$aNaggara, Olivier$$b24
000154282 7001_ $$aGentric, Jean-Christophe$$b25
000154282 7001_ $$aShotar, Eimad$$b26
000154282 7001_ $$00000-0001-7367-8793$$aEugène, François$$b27
000154282 7001_ $$aDesal, Hubert$$b28
000154282 7001_ $$00000-0003-4171-8919$$aWinsvold, Bendik S$$b29
000154282 7001_ $$00000-0001-9540-3256$$aBørte, Sigrid$$b30
000154282 7001_ $$aJohnsen, Marianne Bakke$$b31
000154282 7001_ $$00000-0002-3058-1059$$aBrumpton, Ben M$$b32
000154282 7001_ $$00000-0002-8972-8254$$aSandvei, Marie Søfteland$$b33
000154282 7001_ $$00000-0001-5645-4966$$aWiller, Cristen J$$b34
000154282 7001_ $$aHveem, Kristian$$b35
000154282 7001_ $$00000-0001-5721-0154$$aZwart, John-Anker$$b36
000154282 7001_ $$aVerschuren, W M Monique$$b37
000154282 7001_ $$00000-0001-7906-0038$$aFriedrich, Christoph M$$b38
000154282 7001_ $$00000-0002-5678-4110$$aHirsch, Sven$$b39
000154282 7001_ $$00000-0002-8318-9421$$aSchilling, Sabine$$b40
000154282 7001_ $$00000-0002-1353-7478$$aDauvillier, Jérôme$$b41
000154282 7001_ $$aMartin, Olivier$$b42
000154282 7001_ $$aStroke, HUNT All-In$$b43$$eCollaboration Author
000154282 7001_ $$aGroup, China Kadoorie Biobank Collaborative$$b44$$eCollaboration Author
000154282 7001_ $$aConsortium, BioBank Japan Project$$b45$$eCollaboration Author
000154282 7001_ $$aGroup, ICAN Study$$b46$$eCollaboration Author
000154282 7001_ $$aGroup, CADISP$$b47$$eCollaboration Author
000154282 7001_ $$aGenetics$$b48
000154282 7001_ $$aHaemorrhage, Observational Subarachnoid$$b49$$eCollaboration Author
000154282 7001_ $$aConsortium, International Stroke Genetics$$b50$$eCollaboration Author
000154282 7001_ $$00000-0002-6950-4210$$aJones, Gregory T$$b51
000154282 7001_ $$00000-0002-6180-3611$$aBown, Matthew J$$b52
000154282 7001_ $$00000-0002-3439-0559$$aKo, Nerissa U$$b53
000154282 7001_ $$00000-0002-1937-354X$$aKim, Helen$$b54
000154282 7001_ $$00000-0002-6759-0944$$aColeman, Jonathan R I$$b55
000154282 7001_ $$aBreen, Gerome$$b56
000154282 7001_ $$aZaroff, Jonathan G$$b57
000154282 7001_ $$00000-0002-8495-4578$$aKlijn, Catharina J M$$b58
000154282 7001_ $$aMalik, Rainer$$b59
000154282 7001_ $$0P:(DE-2719)2000030$$aDichgans, Martin$$b60$$udzne
000154282 7001_ $$aSargurupremraj, Muralidharan$$b61
000154282 7001_ $$aTatlisumak, Turgut$$b62
000154282 7001_ $$00000-0001-9088-234X$$aAmouyel, Philippe$$b63
000154282 7001_ $$00000-0001-8675-7968$$aDebette, Stéphanie$$b64
000154282 7001_ $$aRinkel, Gabriel J E$$b65
000154282 7001_ $$aWorrall, Bradford B$$b66
000154282 7001_ $$aPera, Joanna$$b67
000154282 7001_ $$aSlowik, Agnieszka$$b68
000154282 7001_ $$aGaál-Paavola, Emília I$$b69
000154282 7001_ $$aNiemelä, Mika$$b70
000154282 7001_ $$aJääskeläinen, Juha E$$b71
000154282 7001_ $$avon Und Zu Fraunberg, Mikael$$b72
000154282 7001_ $$00000-0002-1264-7667$$aLindgren, Antti$$b73
000154282 7001_ $$aBroderick, Joseph P$$b74
000154282 7001_ $$00000-0003-2074-1861$$aWerring, David J$$b75
000154282 7001_ $$aWoo, Daniel$$b76
000154282 7001_ $$00000-0001-7751-2280$$aRedon, Richard$$b77
000154282 7001_ $$00000-0002-3586-2757$$aBijlenga, Philippe$$b78
000154282 7001_ $$aKamatani, Yoichiro$$b79
000154282 7001_ $$00000-0001-5572-9657$$aVeldink, Jan H$$b80
000154282 7001_ $$00000-0002-5396-2989$$aRuigrok, Ynte M$$b81
000154282 7001_ $$aBian, Zheng$$b82
000154282 7001_ $$aChen, Junshi$$b83
000154282 7001_ $$aChen, Yiping$$b84
000154282 7001_ $$aClarke, Robert$$b85
000154282 7001_ $$aCollins, Rory$$b86
000154282 7001_ $$aGuo, Yu$$b87
000154282 7001_ $$aHan, Xiao$$b88
000154282 7001_ $$aHill, Michael$$b89
000154282 7001_ $$aLiu, Depei$$b90
000154282 7001_ $$aLv, Jun$$b91
000154282 7001_ $$aMillwood, Iona$$b92
000154282 7001_ $$aPeto, Richard$$b93
000154282 7001_ $$aSansome, Sam$$b94
000154282 7001_ $$aWalters, Robin$$b95
000154282 7001_ $$aYang, Xiaoming$$b96
000154282 7001_ $$aYu, Canqing$$b97
000154282 7001_ $$aBonner, Stephen$$b98
000154282 7001_ $$aWalsh, Daniel$$b99
000154282 7001_ $$aBulters, Diederik$$b100
000154282 7001_ $$aKitchen, Neil$$b101
000154282 7001_ $$aBrown, Martin$$b102
000154282 7001_ $$aGrieve, Joan$$b103
000154282 7001_ $$aDichgans, Martin$$b104
000154282 773__ $$0PERI:(DE-600)1494946-5$$a10.1038/s41588-020-00725-7$$gVol. 52, no. 12, p. 1303 - 1313$$n12$$p1303 - 1313$$tNature genetics$$v52$$x1546-1718$$y2020
000154282 8564_ $$uhttps://www.nature.com/articles/s41588-020-00725-7
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