WG purpose and aims
Aneurysmal subarachnoid hemorrhage (aSAH) is a type of stroke caused by the rupture of an intracranial aneurysm. aSAH can be prevented by treating an aneurysm before it ruptures. The aim of the Intracranial Aneurysm (IA) Working Group is to understand how genomics influences the risk, severity, and outcome of aSAH. We also explore if novel genetic risk factors can lead to new biomarkers and therapeutic strategies, and improve risk prediction for individuals at high risk of aSAH. Since aSAH occurs more often in women than in men, we are also interested in identifying sex-specific genetic risk factors. Additionally, we are harmonizing genotype and clinical data, including imaging data, and making them FAIR. This process will facilitate studies investigating the genetic influences on aSAH and intracranial aneurysm phenotypes.
What does the WG do?
The working group meets once every 3 months and during the pre-meeting of the ISGC workshops. The research conducted within the WG is an important part of the daily work of the WG leaders Philippe Bijlenga en Ynte Ruigrok and many of the members. During the meeting, the progress of the joint projects is discussed and opportunities for new studies to be initiated and grant applications are discussed.
Past successes/output
- Bakker MK, Kanning JP, Abraham G, Martinsen AE, Winsvold BS, Zwart JA, Bourcier R, Sawada T, Koido M, Kamatani Y, Morel S, Amouyel P, Debette S, Bijlenga P, Berrandou T, Ganesh SK, Bouatia-Naji N, Jones G, Bown M, Rinkel GJE, Veldink JH, Ruigrok YM; HUNT All-In Stroke, CADISP group, International Consortium for Blood Pressure, International Headache Genetics Consortium, International Stroke Genetics Consortium (ISGC) Intracranial Aneurysm Working Group. Genetic Risk Score for Intracranial Aneurysms: Prediction of Subarachnoid Hemorrhage and Role in Clinical Heterogeneity. Stroke. 2023 Mar;54(3):810-818. doi: 10.1161/STROKEAHA.122.040715.
- Gaastra B, Alexander S, Bakker MK, Bhagat H, Bijlenga P, Blackburn SL, Collins MK, Doré S, Griessenauer CJ, Hendrix P, Hong EP, Hostettler IC, Houlden H, IIhara K, Jeon JP, Kim BJ, Li J, Morel S, Nyquist P, Ren D, Ruigrok YM, Werring D, Tapper W, Galea I, Bulters D. A Genome-Wide Association Study of Outcome After Aneurysmal Subarachnoid Haemorrhage: Discovery Analysis. Transl Stroke Res. 2023 Oct;14(5):681-687. doi: 10.1007/s12975-022-01095-4.
- Morel S, Hostettler IC, Spinner GR, Bourcier R, Pera J, Meling TR, Alg VS, Houlden H, Bakker MK, Van’t Hof F, Rinkel GJE, Foroud T, Lai D, Moomaw CJ, Worrall BB, Caroff J, Constant-Dits-Beaufils P, Karakachoff M, Rimbert A, Rouchaud A, Gaal-Paavola EI, Kaukovalta H, Kivisaari R, Laakso A, Jahromi BR, Tulamo R, Friedrich CM, Dauvillier J, Hirsch S, Isidor N, Kulcsàr Z, Lövblad KO, Martin O, Machi P, Mendes Pereira V, Rüfenacht D, Schaller K, Schilling S, Slowik A, Jaaskelainen JE, von Und Zu Fraunberg M, Jiménez-Conde J, Cuadrado-Godia E, Soriano-Tárraga C, Millwood IY, Walters RG, The neurIST Project, The Ican Study Group, Genetics And Observational Subarachnoid Haemorrhage Gosh Study Investigators, International Stroke Genetics Consortium Isgc, Kim H, Redon R, Ko NU, Rouleau GA, Lindgren A, Niemelä M, Desal H, Woo D, Broderick JP, Werring DJ, Ruigrok YM, Bijlenga P. Intracranial Aneurysm Classifier Using Phenotypic Factors: An International Pooled Analysis. J Pers Med. 2022 Aug 30;12(9):1410. doi: 10.3390/jpm12091410.
- Gaastra B, Alexander S, Bakker MK, Bhagat H, Bijlenga P, Blackburn S, Collins MK, Doré S, Griessenauer C, Hendrix P, Hong EP, Hostettler IC, Houlden H, IIhara K, Jeon JP, Kim BJ, Kumar M, Morel S, Nyquist P, Ren D, Ruigrok YM, Werring D, Galea I, Bulters D, Tapper W. Genome-Wide Association Study of Clinical Outcome After Aneurysmal Subarachnoid Haemorrhage: Protocol. Transl Stroke Res. 2022 Aug;13(4):565-576. doi: 10.1007/s12975-021-00978-2.
- Bakker MK, van der Spek RAA, van Rheenen W, Morel S, Bourcier R, Hostettler IC, Alg VS, van Eijk KR, Koido M, Akiyama M, Terao C, Matsuda K, Walters RG, Lin K, Li L, Millwood IY, Chen Z, Rouleau GA, Zhou S, Rannikmäe K, Sudlow CLM, Houlden H, van den Berg LH, Dina C, Naggara O, Gentric JC, Shotar E, Eugène F, Desal H, Winsvold BS, Børte S, Johnsen MB, Brumpton BM, Sandvei MS, Willer CJ, Hveem K, Zwart JA, Verschuren WMM, Friedrich CM, Hirsch S, Schilling S, Dauvillier J, Martin O; HUNT All-In Stroke; China Kadoorie Biobank Collaborative Group; BioBank Japan Project Consortium; ICAN Study Group; CADISP Group; Genetics and Observational Subarachnoid Haemorrhage (GOSH) Study investigators; International Stroke Genetics Consortium (ISGC); Jones GT, Bown MJ, Ko NU, Kim H, Coleman JRI, Breen G, Zaroff JG, Klijn CJM, Malik R, Dichgans M, Sargurupremraj M, Tatlisumak T, Amouyel P, Debette S, Rinkel GJE, Worrall BB, Pera J, Slowik A, Gaál-Paavola EI, Niemelä M, Jääskeläinen JE, von Und Zu Fraunberg M, Lindgren A, Broderick JP, Werring DJ, Woo D, Redon R, Bijlenga P, Kamatani Y, Veldink JH, Ruigrok YM. Genome-wide association study of intracranial aneurysms identifies 17 risk loci and genetic overlap with clinical risk factors. Nat Genet. 2020 Dec;52(12):1303-1313. doi: 10.1038/s41588-020-00725-7.
Summary statistics for the GWAS meta-analyses, including effective sample size per SNP, can be accessed through Figshare (https://doi.org/10.6084/m9.figshare.11303372) and through the Cerebrovascular Disease Knowledge Portal (http://www.cerebrovascularportal.org).
Regarding the phenotype part of our work we use the @neurIST protocol that defines the factors and data collection and make the data FAIR: https://clinicaltrials.gov/study/NCT05526352?term=neurIST&rank=1
WG lead
Interested researchers, please reach out to us via here to join the WG and/or discuss collaboration opportunities:
Prof dr Philippe Bijlenga, neurosurgeon, dept of Neurosurgery, Hôpitaux universitaires de Genève, Geneva, Switzerland.
Prof dr Ynte Ruigrok, stroke neurologist, dept of Neurology, University Medical Center Utrecht, the Netherlands.