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47 results on '"von Und Zu Fraunberg, Mikael"'

1. Acute evacuation of 54 intracerebral hematomas (aICH) during the microsurgical clipping of a ruptured middle cerebral artery bifurcation aneurysm—illustration of the individual clinical courses and outcomes with a serial brain CT/MRI panel until 12 months

Author

Autio, Anniina H., Paavola, Juho, Tervonen, Joona, Lång, Maarit, Elomaa, Antti-Pekka, Huuskonen, Terhi J., Huttunen, Jukka, Kärkkäinen, Virve, von Und Zu Fraunberg, Mikael, Lindgren, Antti E., Koivisto, Timo, Kurola, Jouni, Jääskeläinen, Juha E., and Kämäräinen, Olli-Pekka

Published
2024
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2. Should individual timeline and serial CT/MRI panels of all patients be presented in acute brain insult cohorts? A pilot study of 45 patients with decompressive craniectomy after aneurysmal subarachnoid hemorrhage

Author

Autio, Anniina H., Paavola, Juho, Tervonen, Joona, Lång, Maarit, Huuskonen, Terhi J., Huttunen, Jukka, Kärkkäinen, Virve, von Und Zu Fraunberg, Mikael, Lindgren, Antti E., Koivisto, Timo, Kurola, Jouni, Jääskeläinen, Juha E., and Kämäräinen, Olli-Pekka

Published
2023
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4. Genome-wide association study of intracranial aneurysms identifies 17 risk loci and genetic overlap with clinical risk factors

Author

Bakker, Mark K, van der Spek, Rick AA, 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 LM, 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, WM 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 RI, Breen, Gerome, Zaroff, Jonathan G, Klijn, Catharina JM, Malik, Rainer, Dichgans, Martin, Sargurupremraj, Muralidharan, Tatlisumak, Turgut, Amouyel, Philippe, Debette, Stéphanie, Rinkel, Gabriel JE, 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, and Ruigrok, Ynte M

Subjects
Genetics, Brain Disorders, Human Genome, Clinical Research, Prevention, Stroke, Neurosciences, Aetiology, 2.1 Biological and endogenous factors, Cardiovascular, Asian People, Blood Pressure, Case-Control Studies, Endothelial Cells, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Hypertension, Intracranial Aneurysm, Polymorphism, Single Nucleotide, Risk Factors, Smoking, Subarachnoid Hemorrhage, White People, 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, Biological Sciences, Medical and Health Sciences, Developmental Biology
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.

Published
2020

6. Microwave Technique for Linear Skull Fracture Detection—Simulation and Experimental Study Using Realistic Human Head Models.

Author

Särestöniemi, Mariella, Singh, Daljeet, von und zu Fraunberg, Mikael, and Myllylä, Teemu

Subjects
SKULL fractures, BODY area networks, FRACTURE healing, BONE fractures, ELECTRICAL load
Abstract

Microwave (MW) sensing is regarded as a promising technique for various medical monitoring and diagnostic applications due to its numerous advantages and the potential to be developed into a portable device for use outside hospital settings. The detection of skull fractures and the monitoring of their healing process would greatly benefit from a rapidly and frequently usable application that can be employed outside the hospital. This paper presents a simulation- and experiment-based study on skull fracture detection with the MW technique using realistic models for the first time. It also presents assessments on the most promising frequency ranges for skull fracture detection within the Industrial, Scientific and Medical (ISM) and ultrawideband (UWB) ranges. Evaluations are carried out with electromagnetic simulations using different head tissue layer models corresponding to different locations in the human head, as well as an anatomically realistic human head simulation model. The measurements are conducted with a real human skull combined with tissue phantoms developed in our laboratory. The comprehensive evaluations show that fractures cause clear differences in antenna and channel parameters (S11 and S21). The difference in S11 is 0.1–20 dB and in S21 is 0.1–30 dB, depending on the fracture width and location. Skull fractures with a less than 1 mm width can be detected with microwaves at different fracture locations. The detectability is frequency dependent. Power flow representations illustrate how fractures impact on the signal propagation at different frequencies. MW-based detection of skull fractures provides the possibility to (1) detect fractures using a safe and low-cost portable device, (2) monitor the healing-process of fractures, and (3) bring essential information for emerging portable MW-based diagnostic applications that can detect, e.g., strokes. [ABSTRACT FROM AUTHOR]

Published
2024
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9. Genome-Wide Association Study of Intracranial Aneurysm Identifies a New Association on Chromosome 7

Author

Foroud, Tatiana, Lai, Dongbing, Koller, Daniel, Van't Hof, Femke, Kurki, Mitja I, Anderson, Craig S, Brown, Robert D, Connolly, Edward Sander, Eriksson, Johan G, Flaherty, Matthew, Fornage, Myriam, von Und Zu Fraunberg, Mikael, Gaál, Emília I, Laakso, Aki, Hernesniemi, Juha, Huston, John, Jääskeläinen, Juha E, Kiemeney, Lambertus A, Kivisaari, Riku, Kleindorfer, Dawn, Ko, Nerissa, Lehto, Hanna, Mackey, Jason, Meissner, Irene, Moomaw, Charles J, Mosley, Thomas H, Moskala, Marek, Niemelä, Mika, Palotie, Aarno, Pera, Joanna, Rinkel, Gabriel, Ripke, Stephan, Rouleau, Guy, Ruigrok, Ynte, Sauerbeck, Laura, Słowik, Agnieszka, Vermeulen, Sita H, Woo, Daniel, Worrall, Bradford B, and Broderick, Joseph

Subjects
Neurosciences, Human Genome, Stroke, Genetics, Brain Disorders, Biotechnology, Aetiology, 2.1 Biological and endogenous factors, Adult, Aged, Chromosomes, Human, Pair 7, Cohort Studies, Female, Genome-Wide Association Study, Humans, Intracranial Aneurysm, Male, Middle Aged, Polymorphism, Single Nucleotide, Whites, chromosomes, human, pair 7, genome-wide association study, intracranial aneurysm, Familial Intracranial Aneurysm Study Investigators, White People, chromosomes, human, pair 7, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Neurology & Neurosurgery
Abstract

Background and purposeCommon variants have been identified using genome-wide association studies which contribute to intracranial aneurysms (IA) susceptibility. However, it is clear that the variants identified to date do not account for the estimated genetic contribution to disease risk.MethodsInitial analysis was performed in a discovery sample of 2617 IA cases and 2548 controls of white ancestry. Novel chromosomal regions meeting genome-wide significance were further tested for association in 2 independent replication samples: Dutch (717 cases; 3004 controls) and Finnish (799 cases; 2317 controls). A meta-analysis was performed to combine the results from the 3 studies for key chromosomal regions of interest.ResultsGenome-wide evidence of association was detected in the discovery sample on chromosome 9 (CDKN2BAS; rs10733376: P

Published
2014

11. Prevalence of pre‐eclampsia in 265 patients with an intracranial aneurysm, 393 female relatives versus a control cohort: A case–control study.

Author

Kotikoski, Satu, Paavola, Juho, Nurmonen, Heidi J., Kärkkäinen, Virve, Huuskonen, Terhi J., Huttunen, Jukka, Koivisto, Timo, von und zu Fraunberg, Mikael, Jääskeläinen, Juha E., and Lindgren, Antti E.

Subjects
ECLAMPSIA, INTRACRANIAL aneurysms, PREECLAMPSIA, PATIENTS' families, GENETIC disorders, CASE-control method
Abstract

Background and objectives: There is emerging evidence on the connection between pre‐eclampsia and saccular intracranial aneurysms (sIAs). Our aim was to study the prevalence of pre‐eclampsia in sIA patients, their female relatives, and matched controls, and to examine familial sIA disease and familial pre‐eclampsia in sIA patients' families. Methods: We included all female sIA patients in the Kuopio Intracranial Aneurysm Patient and Family Database from 1995 to 2018. First, we identified the sIA patients, their female relatives, and matched population controls with the first birth in 1987 or later and studied the prevalence of pre‐eclampsia. Second, all female sIA patients and all female relatives were analyzed for familial sIA disease and familial pre‐eclampsia. Using the Finnish nationwide health registries, we obtained data on drug purchases, hospital diagnoses, and causes of death. Results: In total, 265 sIA patients, 57 daughters, 167 sisters, 169 nieces, and 546 matched controls had the first birth in 1987 or later. Among them, 29 (11%) sIA patients, 5 (9%) daughters, 10 (6%) sisters, 10 (6%) nieces, and 32 (6%) controls had pre‐eclampsia. Of all the 1895 female sIA patients and 12,141 female relatives, 68 sIA patients and 375 relatives had pre‐eclampsia, including 32 families with familial pre‐eclampsia. Conclusions: Pre‐eclampsia was significantly more common in the sIA patients than in their matched controls. Familial sIA disease and familial pre‐eclampsia co‐occurred in seven families. Further studies of the mechanisms by which pre‐eclampsia could affect the walls of brain arteries and increase the rupture risk in sIA disease are indicated. [ABSTRACT FROM AUTHOR]

Published
2024
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13. Author Correction: Genome-wide association study of intracranial aneurysms identifies 17 risk loci and genetic overlap with clinical risk factors

Author

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., 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., and Ruigrok, Ynte M.

Abstract

Correction to: Nature Genetics https://doi.org/10.1038/s41588-020-00725-7, published online 16 November 2020.

Published
2023

15. Intracranial aneurysm classifier using phenotypic factors : an international pooled analysis

Author

Morel, Sandrine, Hostettler, Isabel C., Spinner, Georg R., Bourcier, Romain, Pera, Joanna, Meling, Torstein, Alg, Varinder, Houlden, Henry, Bakker, Mark, van’t Hof, Femke, Rinkel, Gabriel, Foroud, Tatiana, Lai, Dongbing, Moomaw, Charles, Worrall, Bradford, Caroff, Jildaz, Constant-dits-Beaufils, Pacôme, Karakachoff, Matilde, Rimbert, Antoine, Rouchaud, Aymeric, Gaal-Paavola, Emilia, Kaukovalta, Hanna, Kivisaari, Riku, Laakso, Aki, Jahromi, Behnam, Tulamo, Riikka, Friedrich, Christoph, Dauvillier, Jerome, Hirsch, Sven, Isidor, Nathalie, Kulcsàr, Zolt, Lövblad, Karl, Martin, Olivier, Machi, Paolo, Mendes Pereira, Vitor, Rüfenacht, Daniel, Schaller, Karl, Schilling, Sabine, Slowik, Agnieszka, Jaaskelainen, Juha, von und zu Fraunberg, Mikael, Jiménez-Conde, Jordi, Cuadrado-Godia, Elisa, Soriano-Tárraga, Carolina, Millwood, Iona, Walters, Robin, The @neurIST project, The ICAN Study Group, Genetics and Observational Subarachnoid Haemorrhage (GOSH) Study Investigators, International Stroke Genetics Consortium (ISGC), Kim, Helen, Redon, Richard, Ko, Nerissa, Rouleau, Guy, Lindgren, Antti, Niemelä, Mika, Desal, Hubert, Woo, Daniel, Broderick, Joseph, Werring, David, Ruigrok, Ynte, Bijlenga, Philippe, Morel, Sandrine, Hostettler, Isabel C., Spinner, Georg R., Bourcier, Romain, Pera, Joanna, Meling, Torstein, Alg, Varinder, Houlden, Henry, Bakker, Mark, van’t Hof, Femke, Rinkel, Gabriel, Foroud, Tatiana, Lai, Dongbing, Moomaw, Charles, Worrall, Bradford, Caroff, Jildaz, Constant-dits-Beaufils, Pacôme, Karakachoff, Matilde, Rimbert, Antoine, Rouchaud, Aymeric, Gaal-Paavola, Emilia, Kaukovalta, Hanna, Kivisaari, Riku, Laakso, Aki, Jahromi, Behnam, Tulamo, Riikka, Friedrich, Christoph, Dauvillier, Jerome, Hirsch, Sven, Isidor, Nathalie, Kulcsàr, Zolt, Lövblad, Karl, Martin, Olivier, Machi, Paolo, Mendes Pereira, Vitor, Rüfenacht, Daniel, Schaller, Karl, Schilling, Sabine, Slowik, Agnieszka, Jaaskelainen, Juha, von und zu Fraunberg, Mikael, Jiménez-Conde, Jordi, Cuadrado-Godia, Elisa, Soriano-Tárraga, Carolina, Millwood, Iona, Walters, Robin, The @neurIST project, The ICAN Study Group, Genetics and Observational Subarachnoid Haemorrhage (GOSH) Study Investigators, International Stroke Genetics Consortium (ISGC), Kim, Helen, Redon, Richard, Ko, Nerissa, Rouleau, Guy, Lindgren, Antti, Niemelä, Mika, Desal, Hubert, Woo, Daniel, Broderick, Joseph, Werring, David, Ruigrok, Ynte, and Bijlenga, Philippe

Abstract

Intracranial aneurysms (IAs) are usually asymptomatic with a low risk of rupture, but consequences of aneurysmal subarachnoid hemorrhage (aSAH) are severe. Identifying IAs at risk of rupture has important clinical and socio-economic consequences. The goal of this study was to assess the effect of patient and IA characteristics on the likelihood of IA being diagnosed incidentally versus ruptured. Patients were recruited at 21 international centers. Seven phenotypic patient characteristics and three IA characteristics were recorded. The analyzed cohort included 7992 patients. Multivariate analysis demonstrated that: (1) IA location is the strongest factor associated with IA rupture status at diagnosis; (2) Risk factor awareness (hypertension, smoking) increases the likelihood of being diagnosed with unruptured IA; (3) Patients with ruptured IAs in high-risk locations tend to be older, and their IAs are smaller; (4) Smokers with ruptured IAs tend to be younger, and their IAs are larger; (5) Female patients with ruptured IAs tend to be older, and their IAs are smaller; (6) IA size and age at rupture correlate. The assessment of associations regarding patient and IA characteristics with IA rupture allows us to refine IA disease models and provide data to develop risk instruments for clinicians to support personalized decision-making.

Published
2022

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

Author

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, Martinsen, Amy E, Aamodt, Anne Hege, Skogholt, Anne Heidi, Sandset, Else Charlotte, Kristoffersen, Espen S, Ellekjaer, Hanne, Heuch, Ingrid, Nielsen, Jonas Bille, Hagen, Knut, Fritsche, Lars, Thomas, Laurent F., Pedersen, Linda, Gabrielsen, Maiken E, Vigeland, Maria Dehli, Holmen, Oddgeir, Zhou, Wei, Chen, Junshi, Chen (PI), Zhengming, Clarke, Robert, Collins, Rory, Guo, Yu, Li (PI), Liming, Liu, Depei, Lv, Jun, Peto, Richard, Walters, Robin, Avery, Daniel, Boxall, Ruth, Bennett, Derrick, Chang, Yumei, Chen, Yiping, Du, Huaidong, Gan, Wei, Gilbert, Simon, Hacker, Alex, Hill, Michael, Holmes, Michael, Iona, Andri, Kartsonaki, Christiana, Kerosi, Rene, Kong, Ling, Lancaster, Garry, Lewington, Sarah, McDonnell, John, Millwood, Iona, Nie, Qunhua, Ryder, Paul, Sansome, Sam, Schmidt-Valle, Dan, Sherliker, Paul, Sohoni, Rajani, Stevens, Becky, Turnbull, Iain, Wang, Lin, Wright, Neil, Yang, Ling, Yang, Xiaoming, Yao, Pang, Bian, Zheng, Han, Xiao, Hou, Can, Pei, Pei, Liu, Chao, Yu, Canqing, Pang, Zengchang, Gao, Ruqin, Li, Shanpeng, Wang, Shaojie, Liu, Yongmei, Du, Ranran, Cheng, Liang, Tian, Xiaocao, Zhang, Hua, Zhai, Yaoming, Ning, Feng, Sun, Xiaohui, Li, Feifei, Lv, Silu, Wang, Junzheng, Hou, Wei, Zou, Mingyuan, Yan, Shichun, Zhou, Xue, Yu, Bo, Li, Yanjie, Xu, Qinai, Kang, Quan, Guo, Ziyan, Wang, Dan, Hu, Ximin, Chen, Jinyan, Fu, Yan, Wang, Xiaohuan, Weng, Min, Guo, Zhendong, Wu, Shukuan, Li, Yilei, Li, Huimei, Wu, Ming, Zhou, Yonglin, Zhou, Jinyi, Tao, Ran, Yang, Jie, Su, Jian, liu, Fang, Zhang, Jun, Hu, Yihe, Lu, Yan, Ma, Liangcai, Tang, Aiyu, Hua, Yujie, Jin, Jianrong, Liu, Jingchao, Tang, Zhenzhu, Chen, Naying, Huang, Ying, Li, Mingqiang, Meng, Jinhuai, Pan, Rong, Jiang, Qilian, Lan, Jian, Liu, Yun, Wei, Liuping, Zhou, Liyuan, Chen, Ningyu, Wang, Ping, Meng, Fanwen, Qin Sisi Wang, Yulu, Wu, Xianping, Zhang, Ningmei, Chen, Xiaofang, Zhou, Weiwei, Luo, Guojin, Li, Jianguo, Zhong, Xunfu, Liu, Jiaqiu, Sun, Qiang, Ge, Pengfei, Ren, Xiaolan, Dong, Caixia, Zhang, Hui, Mao, Enke, Wang, Xiaoping, Wang, Tao, Zhang, Xi, Zhou, Ding Zhang, Zhou, Gang, Feng, Shixian, Chang, Ling, Fan, Lei, Gao, Yulian, He, Tianyou, Sun, Huarong, He, Pan, Hu, Chen, Zhang, Xukui, Wu, Huifang, Yu, Min, Hu, Ruying, Wang, Hao, Gong, Weiwei, Wang, Meng, Xie, Kaixu, Chen, Lingli, Pan, Dongxia, Gu, Qijun, Huang, Yuelong, Chen, Biyun, Yin, Li, Liu, Huilin, Fu, Zhongxi, Xu, Qiaohua, Xu, Xin, Zhang, Hao, Long, Huajun, Zhang, Libo, Nagai, Akiko, Muto, Kaori, Hirata, Makoto, Morisaki, Takayuki, Yamashita, Yasushi, Kamatani, Yoichiro, Kambara, Yoko, Murakami, Yoshinori, Masumoto, Akihide, Nagayama, Satoshi, Miki, Yoshio, Yoshimori, Kozo, Fujioka, Tomoaki, Takata, Ryo, Yamaji, Ken, Takahashi, Kazuhisa, Asai, Satoshi, Takahashi, Yasuo, Minami, Shiro, Yamaguchi, Hiroki, Koretsune, Yukihiro, Nishizawa, Yasuko, Kodama, Ken, Kutsumi, Hiromu, Suzuki, Takao, Sinozaki, Nobuaki, Murayama, Shigeo, Furukawa, Yoichi, Yamanashi, Yuji, Papagiannaki, Chrisanthi, Piotin, Michel, Trystram, Denis, Edjlali-Goujon, Myriam, Boulouis, Grégoire, Rodriguez, Christine, Hassen, Waghi Ben, Saleme, Suzanna, Mounayer, Charbel, Rouchaud, Aymeric, Levrier, Olivier, Aguettaz, Pierre, Combaz, Xavier, Pasco, Anne, l’Allinec, Vincent, Bintner, Marc, Molho, Marc, Pascale, Gauthier, Chivot, Cyril, Costalat, Vincent, Darganzil, Cyril, Bonafé, Alain, Januel, Anne Christine, Michelozzi, Caterina, Cognard, Christophe, Bonneville, Fabrice, Tall, Philippe, Darcourt, Jean, Biondi, Alessandra, Iosif, Cristina, Ferre, Jean Christophe, Gauvrit, Jean Yves, Eugene, François, Raoult, Hélène, Gentric, Jean Christophe, Ognard, Julien, Anxionnat, René, Gory, Benjamin, Bracard, Serge, Derelle, Anne Laure, Tonnelet, Romain, Spelle, Laurent, Ikka, Léon, Ozanne, Augustin, Gallas, Sophie, Caroff, Jildaz, Achour, Nidal Ben, Moret, Jacques, Chabert, Emmanuel, Berge, Jérôme, Marnat, Gaultier, Barreau, Xavier, Gariel, Florent, Clarencon, Frédéric, Aggour, Mohammed, Ricolfi, Frédéric, Chavent, Adrien, Thouant, Pierre, Lebidinsky, Pablo, Lemogne, Brivael, Herbreteau, Denis, Bibi, Richard, Janot, Kevin, Pierot, Laurent, Soize, Sébastien, Labeyrie, Marc Antoine, Vandendries, Christophe, Kazemi, Appoline, Leclerc, Xavier, Pruvo, Jean Pierre, Bricout, Nicolas, Velasco, Stéphane, Boucebci, Samy, Lemmens, Robin, Pandolfo, Massimo, Bodenant, Marie, Louillet, Fabien, Mas, Jean-Louis, Deltour, Sandrine, Leder, Sara, Léger, Anne, Canaple, Sandrine, Godefroy, Olivier, Giroud, Maurice, Jacquin, Agnès, Moulin, Thierry, Vuillier, Fabrice, Tzourio, Christophe, Santos, Michael Dos, Malik, Rainer, Hausser, Ingrid, Thomas-Feles, Constanze, Weber, Ralf, Grond-Ginsbach, Caspar, Hacke, Werner, Giossi, Alessia, Volonghi, Irene, Costa, Paolo, del Zotto, Elisabetta, Morotti, Andrea, Poli, Loris, Muiesan, Maria Lorenza, Salvetti, Massimo, Rosei, Enrico Agabiti, Lanfranconi, Silvia, Baron, Pierluigi, Ferrarese, Carlo, Susani, Emanuela, Giacalone, Giacomo, Paolucci, Stefano, Palmirotta, Raffaele, Guadagni, Fiorella, Paciaroni, Maurizio, Ballabio, Elena, Parati, Eugenio A., Fluri, Felix, Hatz, Florian, Gisler, Dominique, Amort, Margareth, Bevan, Steve, James, Tom, Olsson, Sandra, Holmegaard, Lukas, Altintas, Ayse, Martin, Juan José, Kittner, Steven, Mitchell, Braxton, Stine, Colin, O’Connell, Jeff, Dueker, Nicole, Koudstaal, Peter J., de Lau, Lonneke M.L., Hofman, Albert, Verhaaren, Benjamin F, Uitterlinden, Andre G, Montaner, Joan, Mendioroz, Maite, Yadav, Sunaina, Khan, Muhammad Saleem, Wilder, Michael, van Dijk, Ewoud, Maaijwee, Noortje, Rutten-Jacobs, Loes, Kramer, Jamie, Malik, Shaneela, Brott, Thomas G, Brown, Robert D, Singleton, Andrew, Hardy, John, Rich, Stephen S, Tanislav, Christian, Jungehülsing, Jan, Werring, David, Alg, Varinder, Hostettler, Isabel, Bonner, Stephen, Walsh, Daniel, Bulters, Diederik, Kitchen, Neil, Brown, Martin, Grieve, Joan, Roberts, Gareth, Jones, Timothy, Critchley, Giles, Sharma, Pankaj, Nelson, Richard, Whitfield, Peter, Ross, Stuart, Patel, Hiren, Eldridge, Paul, Saastamoinen, Kari, Patel, Umang, Lawrance, Enas, Vandabona, Subha, Mendelow, David, Teal, Rachel, Warner, Orlando, Kirkpatrick, Peter, Seshadri, Sudha, Kilarski, Laura, Hyacinth, Hyacinth I, Oliveira, Jamary, Marini, Sandro, Nyquist, Paul, Lewis, Cathryn, Norrving, Bo, Smith, Gustav, Rosand, Jonathan, Biffi, Alessandro, Kourkoulis, Christina, Anderson, Chris, Giese, Anne-Katrin, Bang, Oh Young, Chung, Jong-Won, Kim, Gyeong-Moon, Zhuang, Qishuai, Sheu, Wayne, Smalley, June, Howson, Joanna, Granata, Alessandra, Markus, Hugh, Wardlaw, Joanna, Cole, John, Thalamuthu, Anbupalam, Hopewell, Jemma, Worrall, Bradford, Bis, Josh, Tirschwell, David, Reiner, Alex, Dhar, Raj, Lee, Jin-Moo, Mortenson, Janne, Wassertheil-Smoller, Sylvia, Prasad, Kameshwar, Fisher, Mark, Traenka, Christopher, Wang, Xingwu, Wang, Yongjun, Rouanet, Francois, Sibon, Igor, Sarnowski, Chloé, Maillard, Pauline, Aparicio, Hugo Javier, Dupuis, Josee, Yang, Qiong, Luvizutto, Gustavo, Chasman, Daniel, Rexrode, Kathryn, Harriot, Andrea, Phuah, Chia-Ling, Santo, Gustavo, Gerard, Jen, Liu, Guiyou, Aaron, Sanjith, Christudass, Christhunesa S., Salomi, BSB, Sanghera, Dharambir, Boehme, Amelia, Elkind, Mitchell, Gretarsdottir, Solveig, Lange, Leslie, Rost, Natalia, James, Michael, Stewart, Jill, Goldstein, Larry, Waddy, Salina, Vojinovic, Dina, Ikram, Arfan, Thijs, Vincent, Parati, Eugenio, Boncoraglio, Giorgio, Kooperberg, Charles, Abboud, Sherrine, Zand, Ramin, Bijlenga, Philippe, Selim, Magdy, Happola, Olli, Strbian, Daniel, Tomppo, Liisa, Pathak, Abhishek, Pfeiffer, Dorothea, Aires, de Buenos, de Carvalho, Joao Jose Freitas, Ribeiro, Priscila, Torres, Nuria, Barboza, Miguel, Plomaritoglou, Androniki, Bjorkegren, Johan, Chan, Yu-Feng Yvonne, Gudnason, Villi, Jimenez-Conde, Jordi, Soriano, Carolina, Roquer, Jaume, Bentley, Paul, Tournier-Lasserve, Elisabeth, Dufouil, Carole, Debette, Stephanie, Mishra, Aniket, Wee, Lawrence, Siddiqi, Saima, Wu, Jer-Yuarn, Ko, Tai-Ming, Bione, Silvia, Jood, Katarina, Tatlisumak, Turgut, Arauz, Antonio, Korostynski, Michal, Launer, Lenore, Yue, Suo, bersano, anna, Juchniewicz, Karol Józef, Mateusz, Adamski, Pera, Joanna, Wnuk, Marcin, Levi, Christopher, Gusdon, Aaron, Kostulas, Konstantinos, Maxwell, Jessye, Duering, Marco, Jagiella, Jeremiasz, Hata, Jun, Ninomiya, Toshiharu, Nguyen, Vinh, Thorarinsson, Bjorn Logi, Lee, Tsong-Hai, Rakitko, Alexandr, Dichgans, Martin, Lindgren, Arne, Wasselius, Johan, Drake, Mattias, Stenman, Martin, Ilinca, Andreea, Staals, Julie, Sadr-Nabavi, Ariane, Crawford, Katherine, Lena, Umme, Mateen, Farrah, Ay, Hakan, Wu, Ona, Schirmer, Markus, Romero, Javier, Cramer, Steve, Golland, Polina, Mueller, Bertram, Brown, Robert, Meschia, James, Ross, Owen A., Pare, Guillaume, Chong, Mike, mansour, Ossama yassin, Karaszewski, Bartosz, Enzinger, Christian, Schmidt, Reinhold, Seiler, Stephan, Pichler, Alexander, Ovbiagele, Bruce, Yamada, Yoshiji, Rundek, Tatjana, Blanton, Susan, P, John, Chern, Joseph, O'Donnell, Chris, Corriveau, Roderick, Bhattacharya, Pallab, Gwinn, Katrina, CHANDRA, BHARATENDU, Chen, Christopher, Kalaria, Raj, Koenig, Jim, Singh, Om Prakash, Olugbodi, Akintomi, Giralt, Eva, Saleheen, Danish, de Leeuw, Frank-Erik, Klijn, Karin, Olesen, Jes, Kubo, Michiaki, Spence, David, Pedersen, Annie, Olsson, Maja, Martín, Juan José, Braga, Gabriel, Xu, Huichun, Assimes, Tim, Raskurazhev, Anton, Lee, Wei Ling, Burri, Philippe, Frid, Petrea, GmbH, Heilbronn, Deng, Zhen, Habibi-koolaee, Mahdi, Vijayan, Murali, Leung, Thomas, Wong, Lawrence, Mok, Vincent, Choy, Richard, Jern, Christina, Lebedeva, Elena, Farrall, Martin, Jiayuan, Xu, Loo, Keat Wei, Rinkel, Gabriel, Magnus, Rudolf, Goncalves, Anderson, Franca, Paulo, Cendes, Iscia, Carrera, Caty, Fernandez-Cadenas, Israel, Kim, Helen, Rolfs, Arndt, Owolabi, Mayowa, Bakker, Mark, Ruigrok, Ynte, Hauer, Allard, Pulit, Sara L., Algra, Ale, van der Laan, Sander W., Macleod, Mary, Howard, George, Tiwari, Hemant, Irvin, Ryan, Albright, Karen C., Perry, Rodney, Kidwell, Chelsea, Pavlovic, Aleksandra, Sargurupremraj, Murali, Schilling, Sabrina, Pezzini, Alessandro, Abd-Allah, Foad, DeCarli, Charles, Liebeskind, David, Traylor, Matthew, Tan, Rhea, Danesh, John, Larsson, Susanna C., Rutten, Loes, Donatti, Amanda, Avelar, Wagner, Broderick, Joseph, Woo, Daniel, Kissela, Brett, Ibenez, Laura Garcia, Salman, Rustam, Sudlow, Cathie, McDonough, Caitrin Wheeler, Silliman, Scott, Magvanjav, Oyunbileg, van Agtmael, Tom, Walters, Matthew, Lorentzen, Erik, Stanne, Tara, Olsson, Martina, Nakagawa, Kazuma, Akinyemi, Rufus, Cotlatciuc, Ioana, O'Connell, Jeff, Sparks, Mary, Sorkin, John, Dave, Tushar, Naylor, Jill, Brown, Devin, Du, Rose, Kulik, Tobias B., Attia, John, Faber, James E, Rothwell, Peter, Márquez, Elsa Valdés, Mancuso, Michelangelo, Souza, Doralina Brum, de Silva, Ranil, Vibo, Riina, Korv, Janika, Maguire, Jane, Fornage, Myriam, Illoh, Kachikwu, Milewicz, Dianna, Majersik, Jennifer, DeHavenon, Adam, Kalani, Yashar, Alexander, Matthew, Cushman, Mary, Sale, Michele, Owens, Debra, Keene, Keith, Rich, Stephe, Psaty, Bruce, Longstreth, Will, Atadzhanov, Masharip, Wolfe, Stacey Quintero, Langefeld, Carl, Bushnell, Cheryl, Cruchaga, Carlos, Konrad, Jan, Liu, Junfeng, Sheth, Kevin, Falcone, Guido, Donahue J, Kathleen, Jones, Gregory T., Bown, Matthew J., Ko, Nerissa U., Coleman, Jonathan R.I., Breen, Gerome, Zaroff, Jonathan G., Klijn, Catharina J.M., Sargurupremraj, Muralidharan, Amouyel, Philippe, Debette, Stéphanie, Rinkel, Gabriel J.E., Worrall, Bradford B., Slowik, Agnieszka, Gaál-Paavola, Emilia I., Niemelä, Mika, Jääskeläinen, Juha E., von Und Zu Fraunberg, Mikael, Lindgren, Antti, Broderick, Joseph P., Werring, David J., Redon, Richard, Veldink, Jan H., Ruigrok, Ynte M., Stroke, HUNT All-In, Group, China Kadoorie Biobank Collaborative, Consortium, BioBank Japan Project, Group, ICAN Study, Group, CADISP, investigators, Genetics and Observational Subarachnoid Haemorrhage (GOSH) Study, (ISGC), International Stroke Genetics Consortium, Morel, Sandrine, and Bijlenga, Philippe Alexandre Pierre

Subjects
genetics [Blood Pressure], Medizin, Genome-wide association study, Blood Pressure, Disease, ddc:616.07, Bioinformatics, 616: Innere Medizin und Krankheiten, 0302 clinical medicine, Risk Factors, physiopathology [Hypertension], genetics [Genetic Predisposition to Disease], Genetic risk factor, Stroke, 0303 health sciences, Smoking, genetics [Smoking], genetics [Intracranial Aneurysm], Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], Cerebrovascular disorder, 3. Good health, genetics [European Continental Ancestry Group], Hypertension, genetics [Polymorphism, Single Nucleotide], Subarachnoid hemorrhage, pathology [Intracranial Aneurysm], genetics [White People], Biology, Genetic correlation, pathology [Endothelial Cells], Polymorphism, Single Nucleotide, Article, White People, 03 medical and health sciences, Aneurysm, Asian People, ddc:570, Genetics, medicine, Humans, Genetic Predisposition to Disease, cardiovascular diseases, 030304 developmental biology, genetics [Subarachnoid Hemorrhage], genetics [Asian Continental Ancestry Group], 572: Biochemie, genetics [Asian People], pathology [Subarachnoid Hemorrhage], adverse effects [Smoking], Endothelial Cells, Subarachnoid Hemorrhage, medicine.disease, Intracranial aneurysm, Genetic architecture, ddc:616.8, Case-Control Studies, genetics [Hypertension], 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract

An author correction to this article published in December 2020 is available at https://doi.org/10.1038/s41588-020-00760-4. 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.

Published
2021
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27. Author Correction: Genome-wide association study of intracranial aneurysms identifies 17 risk loci and genetic overlap with clinical risk factors

Author

Bakker, Mark K, van der Spek, Rick A A, Terao, Chikashi, Bulters, Diederik, Kitchen, Neil, Brown, Martin, Grieve, Joan, Matsuda, Koichi, Walters, Robin G, Lin, Kuang, Li, Liming, Millwood, Iona Y, Chen, Zhengming, Rouleau, Guy A, Zhou, Sirui, Rannikmäe, Kristiina, van Rheenen, Wouter, 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, Morel, Sandrine, 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, Bourcier, Romain, Schilling, Sabine, Dauvillier, Jérôme, Martin, Olivier, Stroke, HUNT All-In, Group, China Kadoorie Biobank Collaborative, Consortium, BioBank Japan Project, Group, ICAN Study, Group, CADISP, Genetics, Haemorrhage, Observational Subarachnoid, Hostettler, Isabel C, Consortium, International Stroke Genetics, 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, Alg, Varinder S, 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, van Eijk, Kristel R, 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, Koido, Masaru, Veldink, Jan H, Ruigrok, Ynte M, Bian, Zheng, Chen, Junshi, Chen, Yiping, Clarke, Robert, Collins, Rory, Guo, Yu, Han, Xiao, Hill, Michael, Akiyama, Masato, Liu, Depei, Lv, Jun, Millwood, Iona, Peto, Richard, Sansome, Sam, Walters, Robin, Yang, Xiaoming, Yu, Canqing, Bonner, Stephen, and Walsh, Daniel

Subjects
572: Biochemie, ddc:570, Medizin, Genetics, MEDLINE, Genome-wide association study, Computational biology, Biology, Clinical risk factor, 616: Innere Medizin und Krankheiten
Abstract

In the version of this article initially published, the following statement was missing from the Acknowledgements: “We are grateful to the GenoBiRD core facility (Biogenouest), the Clinical Investigation Center (INSERM CIC1413) and the Center of Biological Resources in Nantes (BB-0033-00040; CHU Nantes, France) for their assistance in managing and genotyping the ICAN and PREGO biobanks. R.R. was supported by the French Regional Council of Pays-de-la-Loire (VaCaRMe program) and the Agence Nationale de la Recherche (ANR-15-CE17-0008-01 to G.L). H.D. and R.B. were supported by the French Ministry of Health (clinical trial NCT02848495 to H.D.), the Genavie Foundation, the Société Française de Radiologie and the Société Française de Neuroradiologie.” The error has been corrected in the HTML and PDF versions of the article. *Lists of authors and their affiliations appear online. Korrektur zu 10.1038/s41588-020-00725-7

Published
2020
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28. Association of Intracranial Aneurysms With Aortic Aneurysms in 125 Patients With Fusiform and 4253 Patients With Saccular Intracranial Aneurysms and Their Family Members and Population Controls

Author

Kurtelius, Arttu, primary, Väntti, Nelli, additional, Rezai Jahromi, Behnam, additional, Tähtinen, Olli, additional, Manninen, Hannu, additional, Koskenvuo, Juha, additional, Tulamo, Riikka, additional, Kotikoski, Satu, additional, Nurmonen, Heidi, additional, Kämäräinen, Olli‐Pekka, additional, Huttunen, Terhi, additional, Huttunen, Jukka, additional, von und zu Fraunberg, Mikael, additional, Koivisto, Timo, additional, Jääskeläinen, Juha E., additional, and Lindgren, Antti E., additional

Published
2019
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29. TAFFEL: Independent Enrichment Analysis of gene sets

Author

Ylä-Herttuala Seppo, Storvik Markus, Paananen Jussi, Kurki Mitja I, Jääskeläinen Juha E, von und zu Fraunberg Mikael, Wong Garry, and Pehkonen Petri

Subjects
Computer applications to medicine. Medical informatics, R858-859.7, Biology (General), QH301-705.5
Abstract

Abstract Background A major challenge in genomic research is identifying significant biological processes and generating new hypotheses from large gene sets. Gene sets often consist of multiple separate biological pathways, controlled by distinct regulatory mechanisms. Many of these pathways and the associated regulatory mechanisms might be obscured by a large number of other significant processes and thus not identified as significant by standard gene set enrichment analysis tools. Results We present a novel method called Independent Enrichment Analysis (IEA) and software TAFFEL that eases the task by clustering genes to subgroups using Gene Ontology categories and transcription regulators. IEA indicates transcriptional regulators putatively controlling biological functions in studied condition. Conclusions We demonstrate that the developed method and TAFFEL tool give new insight to the analysis of differentially expressed genes and can generate novel hypotheses. Our comparison to other popular methods showed that the IEA method implemented in TAFFEL can find important biological phenomena, which are not reported by other methods.

Published
2011
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30. Secondary hypertension in patients with saccular intracranial aneurysm disease: A population based study

Author

Kotikoski, Satu, primary, Huttunen, Jukka, additional, Huttunen, Terhi J., additional, Helin, Katariina, additional, Frösen, Juhana, additional, Koivisto, Timo, additional, Kurki, Mitja I., additional, von und zu Fraunberg, Mikael, additional, Kunnamo, Ilkka, additional, Jääskeläinen, Juha E., additional, and Lindgren, Antti E., additional

Published
2018
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31. Shared genetic risk factors of intracranial, abdominal, and thoracic aneurysms

Author

van 't Hof, Femke N G, Ruigrok, Ynte M, Lee, Cue Hyunkyu, Ripke, Stephan, Anderson, Graig, de Andrade, Mariza, Baas, Annette F, Blankensteijn, Jan D, Böttinger, Erwin P, Bown, Matthew J, Broderick, Joseph, Bijlenga, Philippe, Carrell, David S, Crawford, Dana C, Crosslin, David R, Ebeling, Christian, Eriksson, Johan G, Fornage, Myriam, Foroud, Tatiana, von Und Zu Fraunberg, Mikael, Friedrich, Christoph M, Gaál, Emília I, Gottesman, Omri, Guo, Dong-Chuan, Harrison, Seamus C, Hernesniemi, Juha, Hofman, Albert, Inoue, Ituro, Jääskeläinen, Juha E, Jones, Gregory T, Kiemeney, Lambertus A L M, Kivisaari, Riku, Ko, Nerissa, Koskinen, Seppo, Kubo, Michiaki, Kullo, Iftikhar J, Kuivaniemi, Helena, Kurki, Mitja I, Laakso, Aki, Lai, Dongbing, Leal, Suzanne M, Lehto, Hanna, LeMaire, Scott A, Low, Siew-Kee, Malinowski, Jennifer, McCarty, Catherine A, Milewicz, Dianna M, Mosley, Thomas H, Rinkel, Gabriël J E, de Bakker, Paul I W, Aneurysm Consortium, and Vascular Research Consortium of New Zealand

Subjects
abdominal aortic aneurysm, thoracic aortic aneurysm, Journal Article, intracranial aneurysm, genome wide association study
Abstract

Background--Intracranial aneurysms (IAs), abdominal aortic aneurysms (AAAs), and thoracic aortic aneurysms (TAAs) all have a familial predisposition. Given that aneurysm types are known to co-occur, we hypothesized that there may be shared genetic risk factors for IAs, AAAs, and TAAs. Methods and Results--We performed a mega-analysis of 1000 Genomes Project-imputed genome-wide association study (GWAS) data of 4 previously published aneurysm cohorts: 2 IA cohorts (in total 1516 cases, 4305 controls), 1 AAA cohort (818 cases, 3004 controls), and 1 TAA cohort (760 cases, 2212 controls), and observed associations of 4 known IA, AAA, and/or TAA risk loci (9p21, 18q11, 15q21, and 2q33) with consistent effect directions in all 4 cohorts. We calculated polygenic scores based on IA-, AAA-, and TAA-associated SNPs and tested these scores for association to case-control status in the other aneurysm cohorts; this revealed no shared polygenic effects. Similarly, linkage disequilibrium-score regression analyses did not show significant correlations between any pair of aneurysm subtypes. Last, we evaluated the evidence for 14 previously published aneurysm risk singlenucleotide polymorphisms through collaboration in extended aneurysm cohorts, with a total of 6548 cases and 16 843 controls (IA) and 4391 cases and 37 904 controls (AAA), and found nominally significant associations for IA risk locus 18q11 near RBBP8 to AAA (odds ratio [OR]=1.11; P=4.1910-5) and for TAA risk locus 15q21 near FBN1 to AAA (OR=1.07; P=1.1910-3). Conclusions--Although there was no evidence for polygenic overlap between IAs, AAAs, and TAAs, we found nominally significant effects of two established risk loci for IAs and TAAs in AAAs. These two loci will require further replication.

Published
2016

32. Neurofibromatosis type 1 is not associated with subarachnoid haemorrhage

Author

Kurtelius, Arttu, primary, Kallionpää, Roope A., additional, Huttunen, Jukka, additional, Huttunen, Terhi J., additional, Helin, Katariina, additional, Koivisto, Timo, additional, Frösen, Juhana, additional, von und zu Fraunberg, Mikael, additional, Peltonen, Sirkku, additional, Peltonen, Juha, additional, Jääskeläinen, Juha E., additional, and Lindgren, Antti E., additional

Published
2017
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33. Shared Genetic Risk Factors of Intracranial, Abdominal, and Thoracic Aneurysms

Author

University of Helsinki, Clinicum, University of Helsinki, Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Neurokirurgian yksikkö, van't Hof, Femke N. G., Ruigrok, Ynte M., Lee, Cue Hyunkyu, Ripke, Stephan, Anderson, Graig, de Andrade, Mariza, Baas, Annette F., Blankensteijn, Jan D., Bottinger, Erwin P., Bown, Matthew J., Broderick, Joseph, Bijlenga, Philippe, Carrell, David S., Crawford, Dana C., Crosslin, David R., Ebeling, Christian, Eriksson, Johan G., Fornage, Myriam, Foroud, Tatiana, von und zu Fraunberg, Mikael, Friedrich, Christoph M., Gaal, Emilia I., Gottesman, Omri, Guo, Dong-Chuan, Harrison, Seamus C., Hernesniemi, Juha, Hofman, Albert, Inoue, Ituro, Jaaskelainen, Juha E., Jones, Gregory T., Kiemeney, Lambertus A. L. M., Kivisaari, Riku, Ko, Nerissa, Koskinen, Seppo, Kubo, Michiaki, Kullo, Iftikhar J., Kuivaniemi, Helena, Kurki, Mitja I., Laakso, Aki, Lai, Dongbing, Leal, Suzanne M., Lehto, Hanna, LeMaire, Scott A., Low, Siew-Kee, Malinowski, Jennifer, McCarty, Catherine A., Milewicz, Dianna M., Mosley, Thomas H., Nakamura, Yusuke, Nakaoka, Hirofumi, Niemela, Mika, Pacheco, Jennifer, Peissig, Peggy L., Pera, Joanna, Rasmussen-Torvik, Laura, Ritchie, Marylyn D., Rivadeneira, Fernando, van Rij, Andre M., Santos-Cortez, Regie Lyn P., Saratzis, Athanasios, Slowik, Agnieszka, Takahashi, Atsushi, Tromp, Gerard, Uitterlinden, Andre G., Verma, Shefali S., Vermeulen, Sita H., Wang, Gao T., Han, Buhm, Rinkel, Gabriel J. E., de Bakker, Paul I. W., Aneurysm Consortium, Vasc Res Consortium New Zealand, University of Helsinki, Clinicum, University of Helsinki, Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Neurokirurgian yksikkö, van't Hof, Femke N. G., Ruigrok, Ynte M., Lee, Cue Hyunkyu, Ripke, Stephan, Anderson, Graig, de Andrade, Mariza, Baas, Annette F., Blankensteijn, Jan D., Bottinger, Erwin P., Bown, Matthew J., Broderick, Joseph, Bijlenga, Philippe, Carrell, David S., Crawford, Dana C., Crosslin, David R., Ebeling, Christian, Eriksson, Johan G., Fornage, Myriam, Foroud, Tatiana, von und zu Fraunberg, Mikael, Friedrich, Christoph M., Gaal, Emilia I., Gottesman, Omri, Guo, Dong-Chuan, Harrison, Seamus C., Hernesniemi, Juha, Hofman, Albert, Inoue, Ituro, Jaaskelainen, Juha E., Jones, Gregory T., Kiemeney, Lambertus A. L. M., Kivisaari, Riku, Ko, Nerissa, Koskinen, Seppo, Kubo, Michiaki, Kullo, Iftikhar J., Kuivaniemi, Helena, Kurki, Mitja I., Laakso, Aki, Lai, Dongbing, Leal, Suzanne M., Lehto, Hanna, LeMaire, Scott A., Low, Siew-Kee, Malinowski, Jennifer, McCarty, Catherine A., Milewicz, Dianna M., Mosley, Thomas H., Nakamura, Yusuke, Nakaoka, Hirofumi, Niemela, Mika, Pacheco, Jennifer, Peissig, Peggy L., Pera, Joanna, Rasmussen-Torvik, Laura, Ritchie, Marylyn D., Rivadeneira, Fernando, van Rij, Andre M., Santos-Cortez, Regie Lyn P., Saratzis, Athanasios, Slowik, Agnieszka, Takahashi, Atsushi, Tromp, Gerard, Uitterlinden, Andre G., Verma, Shefali S., Vermeulen, Sita H., Wang, Gao T., Han, Buhm, Rinkel, Gabriel J. E., de Bakker, Paul I. W., Aneurysm Consortium, and Vasc Res Consortium New Zealand

Abstract

Background-Intracranial aneurysms (IAs), abdominal aortic aneurysms (AAAs), and thoracic aortic aneurysms (TAAs) all have a familial predisposition. Given that aneurysm types are known to co-occur, we hypothesized that there may be shared genetic risk factors for IAs, AAAs, and TAAs. Methods and Results-We performed a mega-analysis of 1000 Genomes Project-imputed genome-wide association study (GWAS) data of 4 previously published aneurysm cohorts: 2 IA cohorts (in total 1516 cases, 4305 controls), 1 AAA cohort (818 cases, 3004 controls), and 1 TAA cohort (760 cases, 2212 controls), and observed associations of 4 known IA, AAA, and/or TAA risk loci (9p21, 18q11, 15q21, and 2q33) with consistent effect directions in all 4 cohorts. We calculated polygenic scores based on IA-, AAA-, and TAA-associated SNPs and tested these scores for association to case-control status in the other aneurysm cohorts; this revealed no shared polygenic effects. Similarly, linkage disequilibrium-score regression analyses did not show significant correlations between any pair of aneurysm subtypes. Last, we evaluated the evidence for 14 previously published aneurysm risk single-nucleotide polymorphisms through collaboration in extended aneurysm cohorts, with a total of 6548 cases and 16 843 controls (IA) and 4391 cases and 37 904 controls (AAA), and found nominally significant associations for IA risk locus 18q11 near RBBP8 to AAA (odds ratio [OR]= 1.11; P=4.1 x 10(-5)) and for TAA risk locus 15q21 near FBN1 to AAA (OR=1.07; P=1.1 x 10(-3)). Conclusions-Although there was no evidence for polygenic overlap between IAs, AAAs, and TAAs, we found nominally significant effects of two established risk loci for IAs and TAAs in AAAs. These two loci will require further replication.

Published
2016

34. Shared genetic risk factors of intracranial, abdominal, and thoracic aneurysms

Author

Opleiding Neurologie, Brain, ZL Cerebrovasculaire Ziekten Medisch, Circulatory Health, Genetica Klinische Genetica, Neurologie, Hersenen-Medisch 2, CMM Groep Kaaij, Infection & Immunity, JC onderzoeksprogramma Methodologie, Cancer, van 't Hof, Femke N G, Ruigrok, Ynte M, Lee, Cue Hyunkyu, Ripke, Stephan, Anderson, Graig, de Andrade, Mariza, Baas, Annette F, Blankensteijn, Jan D, Böttinger, Erwin P, Bown, Matthew J, Broderick, Joseph, Bijlenga, Philippe, Carrell, David S, Crawford, Dana C, Crosslin, David R, Ebeling, Christian, Eriksson, Johan G, Fornage, Myriam, Foroud, Tatiana, von Und Zu Fraunberg, Mikael, Friedrich, Christoph M, Gaál, Emília I, Gottesman, Omri, Guo, Dong-Chuan, Harrison, Seamus C, Hernesniemi, Juha, Hofman, Albert, Inoue, Ituro, Jääskeläinen, Juha E, Jones, Gregory T, Kiemeney, Lambertus A L M, Kivisaari, Riku, Ko, Nerissa, Koskinen, Seppo, Kubo, Michiaki, Kullo, Iftikhar J, Kuivaniemi, Helena, Kurki, Mitja I, Laakso, Aki, Lai, Dongbing, Leal, Suzanne M, Lehto, Hanna, LeMaire, Scott A, Low, Siew-Kee, Malinowski, Jennifer, McCarty, Catherine A, Milewicz, Dianna M, Mosley, Thomas H, Rinkel, Gabriël J E, de Bakker, Paul I W, Aneurysm Consortium; Vascular Research Consortium of New Zealand, Opleiding Neurologie, Brain, ZL Cerebrovasculaire Ziekten Medisch, Circulatory Health, Genetica Klinische Genetica, Neurologie, Hersenen-Medisch 2, CMM Groep Kaaij, Infection & Immunity, JC onderzoeksprogramma Methodologie, Cancer, van 't Hof, Femke N G, Ruigrok, Ynte M, Lee, Cue Hyunkyu, Ripke, Stephan, Anderson, Graig, de Andrade, Mariza, Baas, Annette F, Blankensteijn, Jan D, Böttinger, Erwin P, Bown, Matthew J, Broderick, Joseph, Bijlenga, Philippe, Carrell, David S, Crawford, Dana C, Crosslin, David R, Ebeling, Christian, Eriksson, Johan G, Fornage, Myriam, Foroud, Tatiana, von Und Zu Fraunberg, Mikael, Friedrich, Christoph M, Gaál, Emília I, Gottesman, Omri, Guo, Dong-Chuan, Harrison, Seamus C, Hernesniemi, Juha, Hofman, Albert, Inoue, Ituro, Jääskeläinen, Juha E, Jones, Gregory T, Kiemeney, Lambertus A L M, Kivisaari, Riku, Ko, Nerissa, Koskinen, Seppo, Kubo, Michiaki, Kullo, Iftikhar J, Kuivaniemi, Helena, Kurki, Mitja I, Laakso, Aki, Lai, Dongbing, Leal, Suzanne M, Lehto, Hanna, LeMaire, Scott A, Low, Siew-Kee, Malinowski, Jennifer, McCarty, Catherine A, Milewicz, Dianna M, Mosley, Thomas H, Rinkel, Gabriël J E, de Bakker, Paul I W, and Aneurysm Consortium; Vascular Research Consortium of New Zealand

Published
2016

36. MicroRNA-Attenuated Clone of Virulent Semliki Forest Virus Overcomes Antiviral Type I Interferon in Resistant Mouse CT-2A Glioma

Author

Martikainen, Miika, primary, Niittykoski, Minna, additional, von und zu Fraunberg, Mikael, additional, Immonen, Arto, additional, Koponen, Susanna, additional, van Geenen, Maartje, additional, Vähä-Koskela, Markus, additional, Ylösmäki, Erkko, additional, Jääskeläinen, Juha E., additional, Saksela, Kalle, additional, and Hinkkanen, Ari, additional

Published
2015
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37. Molecular genetics of variegate porphyria in Finland

Author

von und zu Fraunberg, Mikael, University of Helsinki, Faculty of Medicine, Institute of Clinical Medicine, Helsingin yliopisto, lääketieteellinen tiedekunta, kliininen laitos, and Helsingfors universitet, medicinska fakulteten, institutionen för klinisk medicin

Published
2003

38. Cortical Brain Biopsy in Long-Term Prognostication of 468 Patients with Possible Normal Pressure Hydrocephalus

Author

Leinonen, Ville, Koivisto, Anne M, Alafuzoff, Irina, Pyykkö, Okko T, Rummukainen, Jaana, von Und Zu Fraunberg, Mikael, Jääskeläinen, Juha E, Soininen, Hilkka, Rinne, Jaakko, Savolainen, Sakari, Leinonen, Ville, Koivisto, Anne M, Alafuzoff, Irina, Pyykkö, Okko T, Rummukainen, Jaana, von Und Zu Fraunberg, Mikael, Jääskeläinen, Juha E, Soininen, Hilkka, Rinne, Jaakko, and Savolainen, Sakari

Abstract

Normal pressure hydrocephalus (NPH) can be alleviated by cerebrospinal fluid shunting but the differential diagnosis and patient selection are challenging. Intraventricular intracranial pressure monitoring as part of the diagnostic workup as well as shunting enable to obtain cortical brain biopsies to detect amyloid-β (Aβ) and hyperphosphorylated tau (HPτ), the hallmark lesions of Alzheimer's disease (AD). In possible NPH, Aβ alone indicates an increased risk of AD and when present with HPτ probable AD, but the effect of those brain lesions on survival is not known. The aim of this study was to evaluate the predictive value of brain biopsy for the long-term outcome of possible NPH. Between 1991 and 2006, the Neurosurgery Department of the Kuopio University Hospital evaluated 468 patients for possible NPH by intraventricular intracranial pressure monitoring and frontal cortical brain biopsy immunostained against Aβ and HPτ. All patients were followed up until the end of 2008 (n = 201) or death (n = 267) with a median follow-up of 4.6 years (range 0-17). Logistic regression analysis with Cox models was applied. Out of the 468 cases, Aβ was detected in 197 (42%) cortical biopsies, and together with HPτ in 44 (9%). Aβ alone indicated increased risk of AD and with HPτ probable AD, but it did not affect survival. Vascular aetiology was the most frequent cause of death. Cortical biopsy findings indicate that NPH is at present a heterogeneous syndrome and has notable overlapping with AD. Brain biopsy did not predict survival but may open a novel research window to study the pathobiology of neurodegeneration.

Published
2012
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39. High Risk Population Isolate Reveals Low Frequency Variants Predisposing to Intracranial Aneurysms

Author

Kurki, Mitja I., primary, Gaál, Emília Ilona, additional, Kettunen, Johannes, additional, Lappalainen, Tuuli, additional, Menelaou, Androniki, additional, Anttila, Verneri, additional, van 't Hof, Femke N. G., additional, von und zu Fraunberg, Mikael, additional, Helisalmi, Seppo, additional, Hiltunen, Mikko, additional, Lehto, Hanna, additional, Laakso, Aki, additional, Kivisaari, Riku, additional, Koivisto, Timo, additional, Ronkainen, Antti, additional, Rinne, Jaakko, additional, Kiemeney, Lambertus A. L., additional, Vermeulen, Sita H., additional, Kaunisto, Mari A., additional, Eriksson, Johan G., additional, Aromaa, Arpo, additional, Perola, Markus, additional, Lehtimäki, Terho, additional, Raitakari, Olli T., additional, Salomaa, Veikko, additional, Gunel, Murat, additional, Dermitzakis, Emmanouil T., additional, Ruigrok, Ynte M., additional, Rinkel, Gabriel J. E., additional, Niemelä, Mika, additional, Hernesniemi, Juha, additional, Ripatti, Samuli, additional, de Bakker, Paul I. W., additional, Palotie, Aarno, additional, and Jääskeläinen, Juha E., additional

Published
2014
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40. TAFFEL: Independent Enrichment Analysis of gene sets

Author

Kurki, Mitja I, primary, Paananen, Jussi, additional, Storvik, Markus, additional, Ylä-Herttuala, Seppo, additional, Jääskeläinen, Juha E, additional, von und zu Fraunberg, Mikael, additional, Wong, Garry, additional, and Pehkonen, Petri, additional

Published
2011
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43. Intracranial Aneurysm Risk Locus 5q23.2 Is Associated with Elevated Systolic Blood Pressure.

Author

Gaál, Emília Ilona, Salo, Perttu, Kristiansson, Kati, Rehnström, Karola, Kettunen, Johannes, Sarin, Antti-Pekka, ¨, Mika Niemela, Jula, Antti, Raitakari, Olli T., Lehtimäki, Terho, Eriksson, Johan G., Widen, Elisabeth, nel, Murat Gu ¨, Kurki, Mitja, von und zu Fraunberg, Mikael, Jääskeläinen, Juha E., Hernesniemi, Juha, Järvelin, Marjo-Riitta, Pouta, Anneli, and Newton-Cheh, Christopher

Subjects
GENOMES, GENETICS, GENOMICS, INTRACRANIAL aneurysms, MUSCLE cells
Abstract

Although genome-wide association studies (GWAS) have identified hundreds of complex trait loci, the pathomechanisms of most remain elusive. Studying the genetics of risk factors predisposing to disease is an attractive approach to identify targets for functional studies. Intracranial aneurysms (IA) are rupture-prone pouches at cerebral artery branching sites. IA is a complex disease for which GWAS have identified five loci with strong association and a further 14 loci with suggestive association. To decipher potential underlying disease mechanisms, we tested whether there are IA loci that convey their effect through elevating blood pressure (BP), a strong risk factor of IA. We performed a meta-analysis of four population-based Finnish cohorts (nFIN = 11 266) not selected for IA, to assess the association of previously identified IA candidate loci (n= 19) with BP. We defined systolic BP (SBP), diastolic BP, mean arterial pressure, and pulse pressure as quantitative outcome variables. The most significant result was further tested for association in the ICBP-GWAS cohort of 200 000 individuals. We found that the suggestive IA locus at 5q23.2 in PRDM6 was significantly associated with SBP in individuals of European descent (pFIN = 3.01E-05, pICBP-GWAS = 0.0007, pALL = 8.13E-07). The risk allele of IA was associated with higher SBP. PRDM6 encodes a protein predominantly expressed in vascular smooth muscle cells. Our study connects a complex disease (IA) locus with a common risk factor for the disease (SBP). We hypothesize that common variants in PRDM6 can contribute to altered vascular wall structure, hence increasing SBP and predisposing to IA. True positive associations often fail to reach genome-wide significance in GWAS. Our findings show that analysis of traditional risk factors as intermediate phenotypes is an effective tool for deciphering hidden heritability. Further, we demonstrate that common disease loci identified in a population isolate may bear wider significance. [ABSTRACT FROM AUTHOR]

Published
2012
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44. Clinical and biochemical characteristics and genotype-phenotype correlation in Finnish variegate porphyria patients.

Author

von und zu Fraunberg, Mikael, Timonen, Kaisa, Mustajoki, Pertti, and Kauppinen, Raili

Subjects
*PORPHYRIA, *GENETIC mutation, *PORPHYRINS
Abstract

Variegate porphyria (VP) is an inherited metabolic disease resulting from the partial deficiency of protoporphyrinogen oxidase, the penultimate enzyme in the heme biosynthetic pathway. We have evaluated the clinical and biochemical outcome of 103 Finnish VP patients diagnosed between 1966 and 2001. Fifty-two per cent of patients had experienced clinical symptoms: 40% had photosensitivity, 27% acute attacks and 14% both manifestations. The proportion of patients with acute attacks has decreased dramatically from 38 to 14% in patients diagnosed before and after 1980, whereas the prevalence of skin symptoms had decreased only subtly from 45 to 34%. We have studied the correlation between PPOX genotype and clinical outcome of 90 patients with the three most common Finnish mutations 112T, R152C and 338G→C. The patients with the I12T mutation experienced no photosensitivity and acute attacks were rare (8%). Therefore, the occurrence of photosensitivity was lower in the I12T group compared to the R152C group (P=0.001), whereas no significant differences between the R152C and 338G→C groups could be observed. Biochemical abnormalities were significantly milder suggesting a milder form of the disease in patients with the I12T mutation. In all VP patients, normal excretion of protoporphyrin in faeces in adulthood predicted freedom from both skin symptoms and acute attacks. The most valuable test predicting an increased risk of symptoms was urinary coproporphyrin, but only a substantially increased excretion exceeding 1000 nmol/day was associated with an increased risk of both skin symptoms and acute attacks. All patients with an excretion of more than 1000 nmol/day experienced either skin symptoms, acute attacks, or both. [ABSTRACT FROM AUTHOR]

Published
2002
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45. Shared Genetic Risk Factors of Intracranial, Abdominal, and Thoracic Aneurysms

Author

van ’t Hof, Femke N. G., Ruigrok, Ynte M., Lee, Cue Hyunkyu, Ripke, Stephan, Anderson, Graig, de Andrade, Mariza, Baas, Annette F., Blankensteijn, Jan D., Böttinger, Erwin P., Bown, Matthew J., Broderick, Joseph, Bijlenga, Philippe, Carrell, David S., Crawford, Dana C., Crosslin, David R., Ebeling, Christian, Eriksson, Johan G., Fornage, Myriam, Foroud, Tatiana, von und zu Fraunberg, Mikael, Friedrich, Christoph M., Gaál, Emília I., Gottesman, Omri, Guo, Dong‐Chuan, Harrison, Seamus C., Hernesniemi, Juha, Hofman, Albert, Inoue, Ituro, Jääskeläinen, Juha E., Jones, Gregory T., Kiemeney, Lambertus A. L. M., Kivisaari, Riku, Ko, Nerissa, Koskinen, Seppo, Kubo, Michiaki, Kullo, Iftikhar J., Kuivaniemi, Helena, Kurki, Mitja I., Laakso, Aki, Lai, Dongbing, Leal, Suzanne M., Lehto, Hanna, LeMaire, Scott A., Low, Siew‐Kee, Malinowski, Jennifer, McCarty, Catherine A., Milewicz, Dianna M., Mosley, Thomas H., Nakamura, Yusuke, Nakaoka, Hirofumi, Niemelä, Mika, Pacheco, Jennifer, Peissig, Peggy L., Pera, Joanna, Rasmussen‐Torvik, Laura, Ritchie, Marylyn D., Rivadeneira, Fernando, van Rij, Andre M., Santos‐Cortez, Regie Lyn P., Saratzis, Athanasios, Slowik, Agnieszka, Takahashi, Atsushi, Tromp, Gerard, Uitterlinden, André G., Verma, Shefali S., Vermeulen, Sita H., Wang, Gao T., Han, Buhm, Rinkel, Gabriël J. E., de Bakker, Paul I. W., Verissimo, Ana, Wright, Benjamin J., Bumpstead, Suzannah, Gretarsdottir, Solveig, Badger, Stephen A., Child, Anne H., Clough, Rachel E., Cockerill, Gillian, Hafez, Hany, Scott, D. Julian A., Futers, Simon, Sohrabi, Soroush, Smith, Alberto, Thompson, Matthew M., van Bockxmeer, Frank M., Matthiasson, Stefan E., Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Teijink, Joep A. W., Wijmenga, Cisca, de Graaf, Jacqueline, Kiemeney, Lambertus A., Palmen, Jutta, Smith, Andrew J., Lindholt, Jes S., Bradley, Declan T., Waltham, Matthew, Edkins, Sarah, Gwilliam, Rhian, Hunt, Sarah E., Potter, Simon, Golledge, Jonathan, Eriksson, Per, Norman, Paul E., Powell, Janet T., Stefansson, Kari, Thompson, John R., Humphries, Steve E., Sayers, Robert D., Deloukas, Panos, Samani, Nilesh J., Phillip, L. Victoria, Hill, Geraldine B., Williams, Michael J. A., Thomson, Ian A., Krysa, Jo, Wilkins, Gerard T., Merriman, Tony R., Vasudevan, Thodor M., Lewis, David R., Blair, Ross D., and Hill, Andrew A.

Subjects
abdominal aortic aneurysm, genome wide association study, intracranial aneurysm, thoracic aortic aneurysm, Inflammation, Vascular Biology, Ischemic Stroke
Abstract

Background: Intracranial aneurysms (IAs), abdominal aortic aneurysms (AAAs), and thoracic aortic aneurysms (TAAs) all have a familial predisposition. Given that aneurysm types are known to co‐occur, we hypothesized that there may be shared genetic risk factors for IAs, AAAs, and TAAs. Methods and Results: We performed a mega‐analysis of 1000 Genomes Project‐imputed genome‐wide association study (GWAS) data of 4 previously published aneurysm cohorts: 2 IA cohorts (in total 1516 cases, 4305 controls), 1 AAA cohort (818 cases, 3004 controls), and 1 TAA cohort (760 cases, 2212 controls), and observed associations of 4 known IA, AAA, and/or TAA risk loci (9p21, 18q11, 15q21, and 2q33) with consistent effect directions in all 4 cohorts. We calculated polygenic scores based on IA‐, AAA‐, and TAA‐associated SNPs and tested these scores for association to case‐control status in the other aneurysm cohorts; this revealed no shared polygenic effects. Similarly, linkage disequilibrium–score regression analyses did not show significant correlations between any pair of aneurysm subtypes. Last, we evaluated the evidence for 14 previously published aneurysm risk single‐nucleotide polymorphisms through collaboration in extended aneurysm cohorts, with a total of 6548 cases and 16 843 controls (IA) and 4391 cases and 37 904 controls (AAA), and found nominally significant associations for IA risk locus 18q11 near RBBP8 to AAA (odds ratio [OR]=1.11; P=4.1×10−5) and for TAA risk locus 15q21 near FBN1 to AAA (OR=1.07; P=1.1×10−3). Conclusions: Although there was no evidence for polygenic overlap between IAs, AAAs, and TAAs, we found nominally significant effects of two established risk loci for IAs and TAAs in AAAs. These two loci will require further replication.

Published
2016
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46. Differences in Aneurysm and Patient Characteristics Between Cohorts of Finnish and Dutch Patients With Subarachnoid Hemorrhage

Author

Munster, Caspar E.P. van, von und zu Fraunberg, Mikael, Rinkel, Gabriel J.E., Rinne, Jaako, Koivisto, Timo, and Ronkainen, Antti

Abstract

The high incidence of aneurysmal subarachnoid hemorrhage (aSAH) in Finland may be related to genetic or environmental factors, which may also influence patient and aneurysm characteristics. We compared these characteristics in 2 cohorts in Finland (Kuopio) and the Netherlands (Utrecht).

Published
2008
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47. Intracranial Aneurysm Classifier Using Phenotypic Factors: An International Pooled Analysis.

Author

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, and Bijlenga P

Abstract

Intracranial aneurysms (IAs) are usually asymptomatic with a low risk of rupture, but consequences of aneurysmal subarachnoid hemorrhage (aSAH) are severe. Identifying IAs at risk of rupture has important clinical and socio-economic consequences. The goal of this study was to assess the effect of patient and IA characteristics on the likelihood of IA being diagnosed incidentally versus ruptured. Patients were recruited at 21 international centers. Seven phenotypic patient characteristics and three IA characteristics were recorded. The analyzed cohort included 7992 patients. Multivariate analysis demonstrated that: (1) IA location is the strongest factor associated with IA rupture status at diagnosis; (2) Risk factor awareness (hypertension, smoking) increases the likelihood of being diagnosed with unruptured IA; (3) Patients with ruptured IAs in high-risk locations tend to be older, and their IAs are smaller; (4) Smokers with ruptured IAs tend to be younger, and their IAs are larger; (5) Female patients with ruptured IAs tend to be older, and their IAs are smaller; (6) IA size and age at rupture correlate. The assessment of associations regarding patient and IA characteristics with IA rupture allows us to refine IA disease models and provide data to develop risk instruments for clinicians to support personalized decision-making., Competing Interests: The authors declare no conflict of interest.

Published
2022
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