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

Title:	Genetic Risk Score for Intracranial Aneurysms: Prediction of Subarachnoid Hemorrhage and Role in Clinical Heterogeneity
Authors:	Bakker M. K.; Kanning J. P.; Abraham G.; Martinsen A. E.; Winsvold B. S.; Zwart J. -A.; Bourcier R.; Sawada T.; Koido M.; Kamatani Y.; Morel S.; Amouyel P.; Debette S.; Bijlenga P.; Berrandou T.; Ganesh S. K.; Bouatia-Naji N.; Jones G.; Bown M.; Rinkel G. J. E.; Veldink J. H.; Ruigrok Y. M.; Hege Aamodt A.; Heidi Skogholt A.; Brumpton B. M.; Willer C. J.; Sandset E. C.; Kristoffersen E. S.; Ellekjaer H.; Heuch I.; Nielsen J. B.; Hagen K.; Hveem K.; Fritsche L. G.; Thomas L. F.; Pedersen L. M.; Gabrielsen M. E.; Holmen O. L.; Borte S.; Zhou W.; Abboud S.; Pandolfo M.; Thijs V.; Leys D.; Bodenant M.; Louillet F.; Touze E.; Mas J. -L.; Samson Y.; Leder S.; Leger A.; Deltour S.; Crozier S.; Meresse I.; Canaple S.; Godefroy O.; Giroud M.; Bejot Y.; Decavel P.; Medeiros E.; Montiel P.; Moulin T.; Vuillier F.; Dallongeville J.; Metso A. J.; Metso T.; Tatlisumak T.; Grond-Ginsbach C.; Lichy C.; Kloss M.; Werner I.; Arnold M. -L.; Dos Santos M.; Grau A.; Dichgans M.; Thomas-Feles C.; Weber R.; Brandt T.; Pezzini A.; De Giuli V.; Caria F.; Poli L.; Padovani A.; Bersano A.; Lanfranconi S.; Beretta S.; Ferrarese C.; Giacolone G.; Paolucci S.; Lyrer P.; Engelter S.; Fluri F.; Hatz F.; Gisler D.; Bonati L.; Gensicke H.; Amort M.; Markus H.; Majersik J.; Worrall B.; Southerland A.; Cole J.; Kittner S.; Evangelou E.; Warren H. R.; Gao H.; Ntritsos G.; Dimou N.; Esko T.; Magi R.; Milani L.; Almgren P.; Boutin T.; Ding J.; Giulianini F.; Holliday E. G.; Jackson A. U.; Li-Gao R.; Lin W. -Y.; Luan J.; Mangino M.; Oldmeadow C.; Peter Prins B.; Qian Y.; Sargurupremraj M.; Shah N.; Surendran P.; Theriault S.; Verweij N.; Willems S. M.; Zhao J. -H.; Connell J.; De Mutsert R.; Doney A. S. F.; Farrall M.; Menni C.; Morris A. D.; Noordam R.; Pare G.; Poulter N. R.; Shields D. C.; Stanton A.; Thom S.; Abecasis G.; Amin N.; Arking D. E.; Ayers K. L.; Barbieri C. M.; Batini C.; Bis J. C.; Blake T.; Bochud M.; Boehnke M.; Boerwinkle E.; Boomsma D. I.; Bottinger E. P.; Braund P. S.; Brumat M.; Campbell A.; Campbell H.; Chakravarti A.; Chambers J. C.; Chauhan G.; Ciullo M.; Cocca M.; Collins F.; Cordell H. J.; Davies G.; De Borst M. H.; De Geus E. J.; Deary I. J.; Deelen J.; Del Greco M F.; Yusuf Demirkale C.; Dorr M.; Ehret G. B.; Elosua R.; Enroth S.; Mesut Erzurumluoglu A.; Ferreira T.; Franberg M.; Franco O. H.; Gandin I.; Gasparini P.; Giedraitis V.; Gieger C.; Girotto G.; Goel A.; Gow A. J.; Gudnason V.; Guo X.; Gyllensten U.; Hamsten A.; Harris T. B.; Harris S. E.; Hartman C. A.; Havulinna A. S.; Hicks A. A.; Hofer E.; Hofman A.; Hottenga J. -J.; Huffman J. E.; Hwang S. -J.; Ingelsson E.; James A.; Jansen R.; Jarvelin M. -R.; Joehanes R.; Johansson A.; Johnson A. D.; Joshi P. K.; Jousilahti P.; Wouter Jukema J.; Jula A.; Kahonen M.; Kathiresan S.; Keavney B. D.; Khaw K. -T.; Knekt P.; Knight J.; Kolcic I.; Kooner J. S.; Koskinen S.; Kristiansson K.; Kutalik Z.; Laan M.; Larson M.; Launer L. J.; Lehne B.; Lehtimaki T.; Liewald D. C. M.; Lin L.; Lind L.; Lindgren C. M.; Liu Y.; Loos R. J. F.; Lopez L. M.; Lu Y.; Lyytikainen L. -P.; Mahajan A.; Mamasoula C.; Marrugat J.; Marten J.; Milaneschi Y.; Morgan A.; Morris A. P.; Morrison A. C.; Munson P. J.; Nalls M. A.; Nandakumar P.; Nelson C. P.; Niiranen T.; Nolte I. M.; Nutile T.; Oldehinkel A. J.; Oostra B. A.; O'reilly P. F.; Org E.; Padmanabhan S.; Palmas W.; Palotie A.; Pattie A.; Penninx B. W. J. H.; Perola M.; Peters A.; Polasek O.; Pramstaller P. P.; Tri Nguyen Q.; Raitakari O. T.; Rettig R.; Rice K.; Ridker P. M.; Ried J. S.; Riese H.; Ripatti S.; Robino A.; Rose L. M.; Rotter J. I.; Rudan I.; Ruggiero D.; Saba Y.; Sala C. F.; Salomaa V.; Samani N. J.; Sarin A. -P.; Schmidt R.; Schmidt H.; Shrine N.; Siscovick D.; Smith A. V.; Snieder H.; Sober S.; Sorice R.; Starr J. M.; Stott D. J.; Strachan D. P.; Strawbridge R. J.; Sundstrom J.; Swertz M. A.; Taylor K. D.; Teumer A.; Tobin M. D.; Tomaszewski M.; Toniolo D.; Traglia M.; Trompet S.; Tuomilehto J.; Tzourio C.; Uitterlinden A. G.; Vaez A.; Van Der Most P. J.; Van Duijn C. M.; Verwoert G. C.; Vitart V.; Volker U.; Vollenweider P.; Vuckovic D.; Watkins H.; Wild S. H.; Willemsen G.; Wilson J. F.; Wright A. F.; Yao J.; Zemunik T.; Zhang W.; Attia J. R.; Butterworth A. S.; Chasman D. I.; Conen D.; Cucca F.; Danesh J.; Hayward C.; Howson J. M. M.; Laakso M.; Lakatta E. G.; Langenberg C.; Melander O.; Mook-Kanamori D. O.; Palmer C. N. A.; Risch L.; Scott R. A.; Scott R. J.; Sever P.; Spector T. D.; Van Der Harst P.; Wareham N. J.; Zeggini E.; Levy D.; Munroe P. B.; Newton-Cheh C.; Brown M. J.; Metspalu A.; Psaty B. M.; Wain L. V.; Elliott P.; Caulfield M. J.; Gormley P.; Anttila V.; Palta P.; Pers T. H.; Farh K. -H.; Cuenca-Leon E.; Muona M.; Furlotte N. A.; Kurth T.; Ingason A.; Mcmahon G.; Ligthart L.; Terwindt G. M.; Kallela M.; Freilinger T. M.; Ran C.; Gordon S. G.; Stam A. H.; Steinberg S.; Borck G.; Koiranen M.; Quaye L.; Adams H. H. H.; Wedenoja J.; Hinds D. A.; Buring J. E.; Schurks M.; Gudlaug Hrafnsdottir M.; Stefansson H.; Ring S. M.; Artto V.; Kaunisto M.; Vepsalainen S.; Malik R.; Heath A. C.; Madden P. A. F.; Martin N. G.; Montgomery G. W.; Kurki M. I.; Kals M.; Parn K.; Hamalainen E.; Huang H.; Byrnes A. E.; Franke L.; Huang J.; Stergiakouli E.; Lee P. H.; Sandor C.; Webber C.; Cader Z.; Muller-Myhsok B.; Schreiber S.; Meitinger T.; Eriksson J. G.; Heikkila K.; Loehrer E.; Cherkas L.; Stubhaug A.; Nielsen C. S.; Mannikko M.; Mihailov E.; Gobel H.; Esserlind A. -L.; Francke Christensen A.; Folkmann Hansen T.; Werge T.; Kaprio J.; Aromaa A. J.; Raitakari O.; Arfan Ikram M.; Spector T.; Kubisch C.; Ferrari M. D.; Belin A. C.; Wessman M.; Van Den Maagdenberg A. M. J. M.; Davey Smith G.; Stefansson K.; Eriksson N.; Daly M. J.; Neale B. M.; Olesen J.; Nyholt D. R.; Akiyama M.; Alg V. S.; Broderick J. P.; Dauvillier J.; Desal H.; Dina C.; Friedrich C. M.; Gaal-Paavola E. I.; Gentric J. -C.; Hirsch S.; Hostettler I. C.; Houlden H.; Jaaskelainen J. E.; Johnsen M. B.; Li L.; Lin K.; Lindgren A.; Martin O.; Matsuda K.; Millwood I. Y.; Naggara O.; Niemela M.; Pera J.; Redon R.; Rouleau G. A.; Sandvei M. So.; Schilling S.; Shotar E.; Slowik A.; Terao C.; Verschuren W. M. M.; Walters R. G.; Werring D. J.; Woo D.; Worrall B. B.; Zhou S.
Contributors:	Bakker, M; Kanning, J; Abraham, G; Martinsen, A; Winsvold, B; Zwart, J; Bourcier, R; Sawada, T; Koido, M; Kamatani, Y; Morel, S; Amouyel, P; Debette, S; Bijlenga, P; Berrandou, T; Ganesh, S; Bouatia-Naji, N; Jones, G; Bown, M; Rinkel, G; Veldink, J; Ruigrok, Y; Hege Aamodt, A; Heidi Skogholt, A; Brumpton, B; Willer, C; Sandset, E; Kristoffersen, E; Ellekjaer, H; Heuch, I; Nielsen, J; Hagen, K; Hveem, K; Fritsche, L; Thomas, L; Pedersen, L; Gabrielsen, M; Holmen, O; Borte, S; Zhou, W; Abboud, S; Pandolfo, M; Thijs, V; Leys, D; Bodenant, M; Louillet, F; Touze, E; Mas, J; Samson, Y; Leder, S; Leger, A; Deltour, S; Crozier, S; Meresse, I; Canaple, S; Godefroy, O; Giroud, M; Bejot, Y; Decavel, P; Medeiros, E; Montiel, P; Moulin, T; Vuillier, F; Dallongeville, J; Metso, A; Metso, T; Tatlisumak, T; Grond-Ginsbach, C; Lichy, C; Kloss, M; Werner, I; Arnold, M; Dos Santos, M; Grau, A; Dichgans, M; Thomas-Feles, C; Weber, R; Brandt, T; Pezzini, A; De Giuli, V; Caria, F; Poli, L; Padovani, A; Bersano, A; Lanfranconi, S; Beretta, S; Ferrarese, C; Giacolone, G; Paolucci, S; Lyrer, P; Engelter, S; Fluri, F; Hatz, F; Gisler, D; Bonati, L; Gensicke, H; Amort, M; Markus, H; Majersik, J; Worrall, B
Publisher Information:	Lippincott Williams & Wilkins; US
Publication Year:	2023
Collection:	Università degli Studi di Milano-Bicocca: BOA (Bicocca Open Archive)
Subject Terms:	aneurysmal subarachnoid hemorrhage; genetic heterogeneity; genetic; intracranial aneurysm; risk assessment
Description:	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=-4.82×10-3per year [95% CI, -6.49×10-3to -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.
Document Type:	article in journal/newspaper
File Description:	STAMPA
Language:	English
Relation:	info:eu-repo/semantics/altIdentifier/pmid/36655558; info:eu-repo/semantics/altIdentifier/wos/WOS:000940824000041; volume:54; issue:3; firstpage:810; lastpage:818; numberofpages:9; journal:STROKE; https://hdl.handle.net/10281/476437
DOI:	10.1161/STROKEAHA.122.040715
Availability:	https://hdl.handle.net/10281/476437; https://doi.org/10.1161/STROKEAHA.122.040715
Accession Number:	edsbas.F6403D99
Database:	BASE