Author: "Winsvold, Bendik S" / Topic: humans - Searchworks@Jio Institute Digital Library Search Results

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14 results on '"Winsvold, Bendik S"'

1. Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology

Author: Mullins, Niamh, Forstner, Andreas J, O’Connell, Kevin S, Coombes, Brandon, Coleman, Jonathan RI, Qiao, Zhen, Als, Thomas D, Bigdeli, Tim B, Børte, Sigrid, Bryois, Julien, Charney, Alexander W, Drange, Ole Kristian, Gandal, Michael J, Hagenaars, Saskia P, Ikeda, Masashi, Kamitaki, Nolan, Kim, Minsoo, Krebs, Kristi, Panagiotaropoulou, Georgia, Schilder, Brian M, Sloofman, Laura G, Steinberg, Stacy, Trubetskoy, Vassily, Winsvold, Bendik S, Won, Hong-Hee, Abramova, Liliya, Adorjan, Kristina, Agerbo, Esben, Al Eissa, Mariam, Albani, Diego, Alliey-Rodriguez, Ney, Anjorin, Adebayo, Antilla, Verneri, Antoniou, Anastasia, Awasthi, Swapnil, Baek, Ji Hyun, Bækvad-Hansen, Marie, Bass, Nicholas, Bauer, Michael, Beins, Eva C, Bergen, Sarah E, Birner, Armin, Bøcker Pedersen, Carsten, Bøen, Erlend, Boks, Marco P, Bosch, Rosa, Brum, Murielle, Brumpton, Ben M, Brunkhorst-Kanaan, Nathalie, Budde, Monika, Bybjerg-Grauholm, Jonas, Byerley, William, Cairns, Murray, Casas, Miquel, Cervantes, Pablo, Clarke, Toni-Kim, Cruceanu, Cristiana, Cuellar-Barboza, Alfredo, Cunningham, Julie, Curtis, David, Czerski, Piotr M, Dale, Anders M, Dalkner, Nina, David, Friederike S, Degenhardt, Franziska, Djurovic, Srdjan, Dobbyn, Amanda L, Douzenis, Athanassios, Elvsåshagen, Torbjørn, Escott-Price, Valentina, Ferrier, I Nicol, Fiorentino, Alessia, Foroud, Tatiana M, Forty, Liz, Frank, Josef, Frei, Oleksandr, Freimer, Nelson B, Frisén, Louise, Gade, Katrin, Garnham, Julie, Gelernter, Joel, Giørtz Pedersen, Marianne, Gizer, Ian R, Gordon, Scott D, Gordon-Smith, Katherine, Greenwood, Tiffany A, Grove, Jakob, Guzman-Parra, José, Ha, Kyooseob, Haraldsson, Magnus, Hautzinger, Martin, Heilbronner, Urs, Hellgren, Dennis, Herms, Stefan, Hoffmann, Per, Holmans, Peter A, Huckins, Laura, Jamain, Stéphane, Johnson, Jessica S, and Kalman, Janos L
Subjects: Biological Sciences, Genetics, Biotechnology, Serious Mental Illness, Human Genome, Bipolar Disorder, Neurosciences, Brain Disorders, Mental Health, Aetiology, 2.1 Biological and endogenous factors, Neurological, Mental health, Good Health and Well Being, Case-Control Studies, Chromosomes, Human, Genetic Predisposition to Disease, Genome, Human, Genome-Wide Association Study, Humans, Major Histocompatibility Complex, Multifactorial Inheritance, Phenotype, Quantitative Trait Loci, Risk Factors, HUNT All-In Psychiatry, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract: Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of bipolar disorder subtypes indicated high but imperfect genetic correlation between bipolar disorder type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads and prioritize genes for functional follow-up studies.
Published: 2021

2. 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

3. Shared genetic risk between migraine and coronary artery disease: A genome-wide analysis of common variants.

Author: Winsvold, Bendik S, Bettella, Francesco, Witoelar, Aree, Anttila, Verneri, Gormley, Padhraig, Kurth, Tobias, Terwindt, Gisela M, Freilinger, Tobias M, Frei, Oleksander, Shadrin, Alexey, Wang, Yunpeng, Dale, Anders M, van den Maagdenberg, Arn MJM, Chasman, Daniel I, Nyholt, Dale R, Palotie, Aarno, Andreassen, Ole A, Zwart, John-Anker, and International Headache Genetics Consortium
Subjects: International Headache Genetics Consortium, Humans, Genetic Predisposition to Disease, Phenotype, Polymorphism, Single Nucleotide, Female, Male, Migraine Disorders, Coronary Artery Disease, Genome-Wide Association Study, General Science & Technology
Abstract: Migraine is a recurrent pain condition traditionally viewed as a neurovascular disorder, but little is known of its vascular basis. In epidemiological studies migraine is associated with an increased risk of cardiovascular disease, including coronary artery disease (CAD), suggesting shared pathogenic mechanisms. This study aimed to determine the genetic overlap between migraine and CAD, and to identify shared genetic risk loci, utilizing a conditional false discovery rate approach and data from two large-scale genome-wide association studies (GWAS) of CAD (C4D, 15,420 cases, 15,062 controls; CARDIoGRAM, 22,233 cases, 64,762 controls) and one of migraine (22,120 cases, 91,284 controls). We found significant enrichment of genetic variants associated with CAD as a function of their association with migraine, which was replicated across two independent CAD GWAS studies. One shared risk locus in the PHACTR1 gene (conjunctional false discovery rate for index SNP rs9349379 < 3.90 x 10-5), which was also identified in previous studies, explained much of the enrichment. Two further loci (in KCNK5 and AS3MT) showed evidence for shared risk (conjunctional false discovery rate < 0.05). The index SNPs at two of the three loci had opposite effect directions in migraine and CAD. Our results confirm previous reports that migraine and CAD share genetic risk loci in excess of what would be expected by chance, and highlight one shared risk locus in PHACTR1. Understanding the biological mechanisms underpinning this shared risk is likely to improve our understanding of both disorders.
Published: 2017

4. Genetic Markers of Human Evolution Are Enriched in Schizophrenia

Author: Srinivasan, Saurabh, Bettella, Francesco, Mattingsdal, Morten, Wang, Yunpeng, Witoelar, Aree, Schork, Andrew J, Thompson, Wesley K, Zuber, Verena, Consortium, The International Headache Genetics Consortium The Schizophrenia Working Group of the Psychiatric Genomics, Winsvold, Bendik S, Zwart, John-Anker, Collier, David A, Desikan, Rahul S, Melle, Ingrid, Werge, Thomas, Dale, Anders M, Djurovic, Srdjan, and Andreassen, Ole A
Subjects: Biological Sciences, Biomedical and Clinical Sciences, Genetics, Biological Psychology, Psychology, Pharmacology and Pharmaceutical Sciences, Prevention, Clinical Research, Mental Health, Biotechnology, Schizophrenia, Brain Disorders, Human Genome, Aetiology, 2.1 Biological and endogenous factors, Mental health, Biological Evolution, Brain, Genetic Markers, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Multifactorial Inheritance, Polymorphism, Single Nucleotide, Evolution, GWAS, Human, Neanderthal, Polygenic, Schizophrenia Working Group of the Psychiatric Genomics Consortium, The International Headache Genetics Consortium, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Biological sciences, Biomedical and clinical sciences
Abstract: BackgroundWhy schizophrenia has accompanied humans throughout our history despite its negative effect on fitness remains an evolutionary enigma. It is proposed that schizophrenia is a by-product of the complex evolution of the human brain and a compromise for humans' language, creative thinking, and cognitive abilities.MethodsWe analyzed recent large genome-wide association studies of schizophrenia and a range of other human phenotypes (anthropometric measures, cardiovascular disease risk factors, immune-mediated diseases) using a statistical framework that draws on polygenic architecture and ancillary information on genetic variants. We used information from the evolutionary proxy measure called the Neanderthal selective sweep (NSS) score.ResultsGene loci associated with schizophrenia are significantly (p = 7.30 × 10(-9)) more prevalent in genomic regions that are likely to have undergone recent positive selection in humans (i.e., with a low NSS score). Variants in brain-related genes with a low NSS score confer significantly higher susceptibility than variants in other brain-related genes. The enrichment is strongest for schizophrenia, but we cannot rule out enrichment for other phenotypes. The false discovery rate conditional on the evolutionary proxy points to 27 candidate schizophrenia susceptibility loci, 12 of which are associated with schizophrenia and other psychiatric disorders or linked to brain development.ConclusionsOur results suggest that there is a polygenic overlap between schizophrenia and NSS score, a marker of human evolution, which is in line with the hypothesis that the persistence of schizophrenia is related to the evolutionary process of becoming human.
Published: 2016

5. Genome wide association study identifies variants in NBEA associated with migraine in bipolar disorder

Author: Jacobsen, Kaya K, Nievergelt, Caroline M, Zayats, Tetyana, Greenwood, Tiffany A, Anttila, Verneri, Akiskal, Hagop S, Consortium, BiGS, Consortium, IHG, include:, BiGS Consortium Co-Authors, Kelsoe, John R, McKinney, Rebecca, Shilling, Paul D, Smith, Erin N, Schork, Nicholas J, Bloss, Cinnamon S, Nurnberger, John I, Edenberg, Howard J, Foroud, Tatiana, Koller, Daniel L, Gershon, Elliot S, Badner, Judith A, Liu, Chunyu, Scheftner, William A, Lawson, William B, Nwulia, Evaristus A, Hipolito, Maria, Potash, James, Coryell, William, Rice, John, Byerley, William, McMahon, Francis J, Berrettini, Wade H, Zandi, Peter P, Mahon, Pamela B, McInnis, Melvin G, Zöllner, Sebastian, Zhang, Peng, Craig, David W, Szelinger, Szabolics, Barrett, Thomas B, Schulze, Thomas G, include:, IHG Consortium Co-Authors, Wedenoja, Juho, Kaunisto, Mari A, Heikkilä, Kauko, Kaprio, Jaakko, Wessman, Maija, Kallela, Mikko, Färkkilä, Markus, Artto, Ville, Aromaa, Arpo, Eriksson, Johan G, Winsvold, Bendik S, Zwart, John-Anker, Gormley, Padhraig, Palotie, Aarno, Kurth, Tobias, Rose, Lynda M, Buring, Julie E, Ridker, Paul M, Chasman, Daniel I, Bettella, Francesco, Steinberg, Stacy, Stefansson, Hreinn, Stefansson, Kari, McMahon, George, Davey-Smith, George, Malik, Rainer, Freilinger, Tobias, Wichmann, Heinz Erich, Dichgans, Martin, Muller-Myhsok, Bertram, Meitinger, Thomas, de Vries, Boukje, Terwindt, Gisela, Stam, Anine H, Frants, Rune R, Pelzer, Nadine, Weller, Claudia M, Zielman, Ronald, Ferrari, Michel D, van den Maagdenberg, Arn MJM, Medland, Sarah E, Montgomery, Grant W, Martin, Nicholas G, Nyholt, Dale R, Todt, Unda, Borck, Guntram, Kubisch, Christian, Quaye, Lydia, Williams, Frances MK, Cherkas, Lynn, Koiranen, Markku, Hartikainen, Anna-Liisa, Pouta, Anneli, Jarvelin, Marjo-Riitta, Ikram, M Arfan, and van den Ende, Joyce
Subjects: Biomedical and Clinical Sciences, Headaches, Bipolar Disorder, Human Genome, Genetics, Mental Health, Pain Research, Migraines, Serious Mental Illness, Chronic Pain, Mental Illness, Neurosciences, Brain Disorders, 2.1 Biological and endogenous factors, Neurological, Adult, Carrier Proteins, Comorbidity, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Migraine Disorders, Nerve Tissue Proteins, Polymorphism, Single Nucleotide, Bipolar disorder, Migraine, NBEA, Neurobeachin, BiGS Consortium, IHG Consortium, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Biomedical and clinical sciences, Health sciences, Psychology
Abstract: BackgroundMigraine is a common comorbidity among individuals with bipolar disorder, but the underlying mechanisms for this co-occurrence are poorly understood. The aim of this study was to investigate the genetic background of bipolar patients with and without migraine.MethodsWe performed a genome-wide association analysis contrasting 460 bipolar migraneurs with 914 bipolar patients without migraine from the Bipolar Genome Study (BiGS).ResultsWe identified one genome-wide significant association between migraine in bipolar disorder patients and rs1160720, an intronic single nucleotide polymorphism (SNP) in the NBEA gene (P=2.97 × 10(-8), OR: 1.82, 95% CI: 1.47-2.25), although this was not replicated in a smaller sample of 289 migraine cases.LimitationsOur study is based on self-reported migraine.ConclusionsNBEA encodes neurobeachin, a scaffolding protein primarily expressed in the brain and involved in trafficking of vesicles containing neurotransmitter receptors. This locus has not previously been implicated in migraine per se. We found no evidence of association in data from the GWAS migraine meta-analysis consortium (n=118,710 participants) suggesting that the association might be specific to migraine co-morbid with bipolar disorder.
Published: 2015

6. A saturated map of common genetic variants associated with human height

Author: Yengo, Loïc, Vedantam, Sailaja, Marouli, Eirini, Sidorenko, Julia, Bartell, Eric, Sakaue, Saori, Graff, Marielisa, Eliasen, Anders U, Jiang, Yunxuan, Raghavan, Sridharan, Miao, Jenkai, Arias, Joshua D, Graham, Sarah E, Mukamel, Ronen E, Spracklen, Cassandra N, Yin, Xianyong, Chen, Shyh-Huei, Ferreira, Teresa, Highland, Heather H, Ji, Yingjie, Karaderi, Tugce, Lin, Kuang, Lüll, Kreete, Malden, Deborah E, Medina-Gomez, Carolina, Machado, Moara, Moore, Amy, Rüeger, Sina, Sim, Xueling, Vrieze, Scott, Ahluwalia, Tarunveer S, Akiyama, Masato, Allison, Matthew A, Alvarez, Marcus, Andersen, Mette K, Ani, Alireza, Appadurai, Vivek, Arbeeva, Liubov, Bhaskar, Seema, Bielak, Lawrence F, Bollepalli, Sailalitha, Bonnycastle, Lori L, Bork-Jensen, Jette, Bradfield, Jonathan P, Bradford, Yuki, Braund, Peter S, Brody, Jennifer A, Burgdorf, Kristoffer S, Cade, Brian E, Cai, Hui, Cai, Qiuyin, Campbell, Archie, Cañadas-Garre, Marisa, Catamo, Eulalia, Chai, Jin-Fang, Chai, Xiaoran, Chang, Li-Ching, Chang, Yi-Cheng, Chen, Chien-Hsiun, Chesi, Alessandra, Choi, Seung Hoan, Chung, Ren-Hua, Cocca, Massimiliano, Concas, Maria Pina, Couture, Christian, Cuellar-Partida, Gabriel, Danning, Rebecca, Daw, E Warwick, Degenhard, Frauke, Delgado, Graciela E, Delitala, Alessandro, Demirkan, Ayse, Deng, Xuan, Devineni, Poornima, Dietl, Alexander, Dimitriou, Maria, Dimitrov, Latchezar, Dorajoo, Rajkumar, Ekici, Arif B, Engmann, Jorgen E, Fairhurst-Hunter, Zammy, Farmaki, Aliki-Eleni, Faul, Jessica D, Fernandez-Lopez, Juan-Carlos, Forer, Lukas, Francescatto, Margherita, Freitag-Wolf, Sandra, Fuchsberger, Christian, Galesloot, Tessel E, Gao, Yan, Gao, Zishan, Geller, Frank, Giannakopoulou, Olga, Giulianini, Franco, Gjesing, Anette P, Goel, Anuj, Gordon, Scott D, Gorski, Mathias, Grove, Jakob, Guo, Xiuqing, Gustafsson, Stefan, Haessler, Jeffrey, Hansen, Thomas F, Havulinna, Aki S, Haworth, Simon J, He, Jing, Heard-Costa, Nancy, Hebbar, Prashantha, Hindy, George, Ho, Yuk-Lam A, Hofer, Edith, Holliday, Elizabeth, Horn, Katrin, Hornsby, Whitney E, Hottenga, Jouke-Jan, Huang, Hongyan, Huang, Jie, Huerta-Chagoya, Alicia, Huffman, Jennifer E, Hung, Yi-Jen, Huo, Shaofeng, Hwang, Mi Yeong, Iha, Hiroyuki, Ikeda, Daisuke D, Isono, Masato, Jackson, Anne U, Jäger, Susanne, Jansen, Iris E, Johansson, Ingegerd, Jonas, Jost B, Jonsson, Anna, Jørgensen, Torben, Kalafati, Ioanna-Panagiota, Kanai, Masahiro, Kanoni, Stavroula, Kårhus, Line L, Kasturiratne, Anuradhani, Katsuya, Tomohiro, Kawaguchi, Takahisa, Kember, Rachel L, Kentistou, Katherine A, Kim, Han-Na, Kim, Young Jin, Kleber, Marcus E, Knol, Maria J, Kurbasic, Azra, Lauzon, Marie, Le, Phuong, Lea, Rodney, Lee, Jong-Young, Leonard, Hampton L, Li, Shengchao A, Li, Xiaohui, Li, Xiaoyin, Liang, Jingjing, Lin, Honghuang, Lin, Shih-Yi, Liu, Jun, Liu, Xueping, Lo, Ken Sin, Long, Jirong, Lores-Motta, Laura, Luan, Jian'an, Lyssenko, Valeriya, Lyytikäinen, Leo-Pekka, Mahajan, Anubha, Mamakou, Vasiliki, Mangino, Massimo, Manichaikul, Ani, Marten, Jonathan, Mattheisen, Manuel, Mavarani, Laven, McDaid, Aaron F, Meidtner, Karina, Melendez, Tori L, Mercader, Josep M, Milaneschi, Yuri, Miller, Jason E, Millwood, Iona Y, Mishra, Pashupati P, Mitchell, Ruth E, Møllehave, Line T, Morgan, Anna, Mucha, Soeren, Munz, Matthias, Nakatochi, Masahiro, Nelson, Christopher P, Nethander, Maria, Nho, Chu Won, Nielsen, Aneta A, Nolte, Ilja M, Nongmaithem, Suraj S, Noordam, Raymond, Ntalla, Ioanna, Nutile, Teresa, Pandit, Anita, Christofidou, Paraskevi, Pärna, Katri, Pauper, Marc, Petersen, Eva RB, Petersen, Liselotte V, Pitkänen, Niina, Polašek, Ozren, Poveda, Alaitz, Preuss, Michael H, Pyarajan, Saiju, Raffield, Laura M, Rakugi, Hiromi, Ramirez, Julia, Rasheed, Asif, Raven, Dennis, Rayner, Nigel W, Riveros, Carlos, Rohde, Rebecca, Ruggiero, Daniela, Ruotsalainen, Sanni E, Ryan, Kathleen A, Sabater-Lleal, Maria, Saxena, Richa, Scholz, Markus, Sendamarai, Anoop, Shen, Botong, Shi, Jingchunzi, Shin, Jae Hun, Sidore, Carlo, Sitlani, Colleen M, Slieker, Roderick C, Smit, Roelof AJ, Smith, Albert V, Smith, Jennifer A, Smyth, Laura J, Southam, Lorraine, Steinthorsdottir, Valgerdur, Sun, Liang, Takeuchi, Fumihiko, Tallapragada, Divya Sri Priyanka, Taylor, Kent D, Tayo, Bamidele O, Tcheandjieu, Catherine, Terzikhan, Natalie, Tesolin, Paola, Teumer, Alexander, Theusch, Elizabeth, Thompson, Deborah J, Thorleifsson, Gudmar, Timmers, Paul RHJ, Trompet, Stella, Turman, Constance, Vaccargiu, Simona, Van Der Laan, Sander W, Van Der Most, Peter J, Van Klinken, Jan B, Van Setten, Jessica, Verma, Shefali S, Verweij, Niek, Veturi, Yogasudha, Wang, Carol A, Wang, Chaolong, Wang, Lihua, Wang, Zhe, Warren, Helen R, Bin Wei, Wen, Wickremasinghe, Ananda R, Wielscher, Matthias, Wiggins, Kerri L, Winsvold, Bendik S, Wong, Andrew, Wu, Yang, Wuttke, Matthias, Xia, Rui, Xie, Tian, Yamamoto, Ken, Yang, Jingyun, Yao, Jie, Young, Hannah, Yousri, Noha A, Yu, Lei, Zeng, Lingyao, Zhang, Weihua, Zhang, Xinyuan, Zhao, Jing-Hua, Zhao, Wei, Zhou, Wei, Zimmermann, Martina E, Zoledziewska, Magdalena, Adair, Linda S, Adams, Hieab HH, Aguilar-Salinas, Carlos A, Al-Mulla, Fahd, Arnett, Donna K, Asselbergs, Folkert W, Åsvold, Bjørn Olav, Attia, John, Banas, Bernhard, Bandinelli, Stefania, Bennett, David A, Bergler, Tobias, Bharadwaj, Dwaipayan, Biino, Ginevra, Bisgaard, Hans, Boerwinkle, Eric, Böger, Carsten A, Bønnelykke, Klaus, Boomsma, Dorret I, Børglum, Anders D, Borja, Judith B, Bouchard, Claude, Bowden, Donald W, Brandslund, Ivan, Brumpton, Ben, Buring, Julie E, Caulfield, Mark J, Chambers, John C, Chandak, Giriraj R, Chanock, Stephen J, Chaturvedi, Nish, Chen, Yii-Der Ida, Chen, Zhengming, Cheng, Ching-Yu, Christophersen, Ingrid E, Ciullo, Marina, Cole, John W, Collins, Francis S, Cooper, Richard S, Cruz, Miguel, Cucca, Francesco, Cupples, L Adrienne, Cutler, Michael J, Damrauer, Scott M, Dantoft, Thomas M, De Borst, Gert J, De Groot, Lisette CPGM, De Jager, Philip L, De Kleijn, Dominique PV, Janaka De Silva, H, Dedoussis, George V, Den Hollander, Anneke I, Du, Shufa, Easton, Douglas F, Elders, Petra JM, Eliassen, A Heather, Ellinor, Patrick T, Elmståhl, Sölve, Erdmann, Jeanette, Evans, Michele K, Fatkin, Diane, Feenstra, Bjarke, Feitosa, Mary F, Ferrucci, Luigi, Ford, Ian, Fornage, Myriam, Franke, Andre, Franks, Paul W, Freedman, Barry I, Gasparini, Paolo, Gieger, Christian, Girotto, Giorgia, Goddard, Michael E, Golightly, Yvonne M, Gonzalez-Villalpando, Clicerio, Gordon-Larsen, Penny, Grallert, Harald, Grant, Struan FA, Grarup, Niels, Griffiths, Lyn, Gudnason, Vilmundur, Haiman, Christopher, Hakonarson, Hakon, Hansen, Torben, Hartman, Catharina A, Hattersley, Andrew T, Hayward, Caroline, Heckbert, Susan R, Heng, Chew-Kiat, Hengstenberg, Christian, Hewitt, Alex W, Hishigaki, Haretsugu, Hoyng, Carel B, Huang, Paul L, Huang, Wei, Hunt, Steven C, Hveem, Kristian, Hyppönen, Elina, Iacono, William G, Ichihara, Sahoko, Ikram, M Arfan, Isasi, Carmen R, Jackson, Rebecca D, Jarvelin, Marjo-Riitta, Jin, Zi-Bing, Jöckel, Karl-Heinz, Joshi, Peter K, Jousilahti, Pekka, Jukema, J Wouter, Kähönen, Mika, Kamatani, Yoichiro, Kang, Kui Dong, Kaprio, Jaakko, Kardia, Sharon LR, Karpe, Fredrik, Kato, Norihiro, Kee, Frank, Kessler, Thorsten, Khera, Amit V, Khor, Chiea Chuen, Kiemeney, Lambertus ALM, Kim, Bong-Jo, Kim, Eung Kweon, Kim, Hyung-Lae, Kirchhof, Paulus, Kivimaki, Mika, Koh, Woon-Puay, Koistinen, Heikki A, Kolovou, Genovefa D, Kooner, Jaspal S, Kooperberg, Charles, Köttgen, Anna, Kovacs, Peter, Kraaijeveld, Adriaan, Kraft, Peter, Krauss, Ronald M, Kumari, Meena, Kutalik, Zoltan, Laakso, Markku, Lange, Leslie A, Langenberg, Claudia, Launer, Lenore J, Le Marchand, Loic, Lee, Hyejin, Lee, Nanette R, Lehtimäki, Terho, Li, Huaixing, Li, Liming, Lieb, Wolfgang, Lin, Xu, Lind, Lars, Linneberg, Allan, Liu, Ching-Ti, Liu, Jianjun, Loeffler, Markus, London, Barry, Lubitz, Steven A, Lye, Stephen J, Mackey, David A, Mägi, Reedik, Magnusson, Patrik KE, Marcus, Gregory M, Vidal, Pedro Marques, Martin, Nicholas G, März, Winfried, Matsuda, Fumihiko, McGarrah, Robert W, McGue, Matt, McKnight, Amy Jayne, Medland, Sarah E, Mellström, Dan, Metspalu, Andres, Mitchell, Braxton D, Mitchell, Paul, Mook-Kanamori, Dennis O, Morris, Andrew D, Mucci, Lorelei A, Munroe, Patricia B, Nalls, Mike A, Nazarian, Saman, Nelson, Amanda E, Neville, Matt J, Newton-Cheh, Christopher, Nielsen, Christopher S, Nöthen, Markus M, Ohlsson, Claes, Oldehinkel, Albertine J, Orozco, Lorena, Pahkala, Katja, Pajukanta, Päivi, Palmer, Colin NA, Parra, Esteban J, Pattaro, Cristian, Pedersen, Oluf, Pennell, Craig E, Penninx, Brenda WJH, Perusse, Louis, Peters, Annette, Peyser, Patricia A, Porteous, David J, Posthuma, Danielle, Power, Chris, Pramstaller, Peter P, Province, Michael A, Qi, Qibin, Qu, Jia, Rader, Daniel J, Raitakari, Olli T, Ralhan, Sarju, Rallidis, Loukianos S, Rao, Dabeeru C, Redline, Susan, Reilly, Dermot F, Reiner, Alexander P, Rhee, Sang Youl, Ridker, Paul M, Rienstra, Michiel, Ripatti, Samuli, Ritchie, Marylyn D, Roden, Dan M, Rosendaal, Frits R, Rotter, Jerome I, Rudan, Igor, Rutters, Femke, Sabanayagam, Charumathi, Saleheen, Danish, Salomaa, Veikko, Samani, Nilesh J, Sanghera, Dharambir K, Sattar, Naveed, Schmidt, Börge, Schmidt, Helena, Schmidt, Reinhold, Schulze, Matthias B, Schunkert, Heribert, Scott, Laura J, Scott, Rodney J, Sever, Peter, Shiroma, Eric J, Shoemaker, M Benjamin, Shu, Xiao-Ou, Simonsick, Eleanor M, Sims, Mario, Singh, Jai Rup, Singleton, Andrew B, Sinner, Moritz F, Smith, J Gustav, Snieder, Harold, Spector, Tim D, Stampfer, Meir J, Stark, Klaus J, Strachan, David P, 'T Hart, Leen M, Tabara, Yasuharu, Tang, Hua, Tardif, Jean-Claude, Thanaraj, Thangavel A, Timpson, Nicholas J, Tönjes, Anke, Tremblay, Angelo, Tuomi, Tiinamaija, Tuomilehto, Jaakko, Tusié-Luna, Maria-Teresa, Uitterlinden, Andre G, Van Dam, Rob M, Van Der Harst, Pim, Van Der Velde, Nathalie, Van Duijn, Cornelia M, Van Schoor, Natasja M, Vitart, Veronique, Völker, Uwe, Vollenweider, Peter, Völzke, Henry, Wacher-Rodarte, Niels H, Walker, Mark, Wang, Ya Xing, Wareham, Nicholas J, Watanabe, Richard M, Watkins, Hugh, Weir, David R, Werge, Thomas M, Widen, Elisabeth, Wilkens, Lynne R, Willemsen, Gonneke, Willett, Walter C, Wilson, James F, Wong, Tien-Yin, Woo, Jeong-Taek, Wright, Alan F, Wu, Jer-Yuarn, Xu, Huichun, Yajnik, Chittaranjan S, Yokota, Mitsuhiro, Yuan, Jian-Min, Zeggini, Eleftheria, Zemel, Babette S, Zheng, Wei, Zhu, Xiaofeng, Zmuda, Joseph M, Zonderman, Alan B, Zwart, John-Anker, 23andMe Research Team, VA Million Veteran Program, DiscovEHR (DiscovEHR And MyCode Community Health Initiative), EMERGE (Electronic Medical Records And Genomics Network), Lifelines Cohort Study, PRACTICAL Consortium, Understanding Society Scientific Group, Chasman, Daniel I, Cho, Yoon Shin, Heid, Iris M, McCarthy, Mark I, Ng, Maggie CY, O'Donnell, Christopher J, Rivadeneira, Fernando, Thorsteinsdottir, Unnur, Sun, Yan V, Tai, E Shyong, Boehnke, Michael, Deloukas, Panos, Justice, Anne E, Lindgren, 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Epidemiology, Radiology & Nuclear Medicine, Clinical Genetics, Team, 23andMe Research, Program, VA Million Veteran, Initiative), DiscovEHR (DiscovEHR and 112 MyCode Community Health, Network), eMERGE (Electronic Medical Records and Genomics, Study, Lifelines Cohort, Consortium, The PRACTICAL, Group, Understanding Society Scientific, Yengo, Loïc [0000-0002-4272-9305], Apollo - University of Cambridge Repository, Laboratory Genetic Metabolic Diseases, Laboratory for General Clinical Chemistry, Geriatrics, AMS - Ageing & Vitality, APH - Aging & Later Life, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, ACS - Heart failure & arrhythmias, Psychiatry, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, General practice, ACS - Diabetes & metabolism, Human genetics, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Amsterdam Reproduction & Development (AR&D), Epidemiology and Data Science, Internal medicine, APH - Digital Health, Tampere University, Department of Clinical Chemistry, Clinical Medicine, Department of Clinical Physiology and Nuclear Medicine, Yengo, Loïc, Vedantam, Sailaja, Marouli, Eirini, Sidorenko, Julia, Hypponen, Elina, Hirschhorn, Joel N, Epigenetics of Complex Diseases and Traits, Institute for Molecular Medicine Finland, Helsinki Institute of Life Science HiLIFE, Joint Activities, University of Helsinki, Medicum, Complex Disease Genetics, Samuli Olli Ripatti / Principal Investigator, Helsinki Institute of Life Science HiLIFE, Department of Medicine, HUS Internal Medicine and Rehabilitation, Clinicum, Centre of Excellence in Complex Disease Genetics, Department of Public Health, Faculty Common Matters (Faculty of Social Sciences), Research Programs Unit, HUS Abdominal Center, Tiinamaija Tuomi Research Group, CAMM - Research Program for Clinical and Molecular Metabolism, Departments of Faculty of Veterinary Medicine, Elisabeth Ingrid Maria Widen / Principal Investigator, Genomic Discoveries and Clinical Translation, 23andMe Research Team, VA Million Veteran Program, DiscovEHR (DiscovEHR and MyCode Community Health Initiative), eMERGE (Electronic Medical Records and Genomics Network), Lifelines Cohort Study, PRACTICAL Consortium, Understanding Society Scientific Group, Partida, G.C., Sun, Y., Croteau-Chonka, D., Vonk, J.M., Chanock, S., Le Marchand, L., Bartell, Eric, Sakaue, Saori, Graff, Marielisa, Eliasen, Anders U, Jiang, Yunxuan, Raghavan, Sridharan, Miao, Jenkai, Arias, Joshua D, Graham, Sarah E, Mukamel, Ronen E, Spracklen, Cassandra N, Yin, Xianyong, Chen, Shyh-Huei, Ferreira, Teresa, Highland, Heather H, Ji, Yingjie, Karaderi, Tugce, Lin, Kuang, Lüll, Kreete, Malden, Deborah E, Medina-Gomez, Carolina, Machado, Moara, Moore, Amy, Rüeger, Sina, Sim, Xueling, Vrieze, Scott, Ahluwalia, Tarunveer S, Akiyama, Masato, Allison, Matthew A, Alvarez, Marcu, Andersen, Mette K, Ani, Alireza, Appadurai, Vivek, Arbeeva, Liubov, Bhaskar, Seema, Bielak, Lawrence F, Bollepalli, Sailalitha, Bonnycastle, Lori L, Bork-Jensen, Jette, Bradfield, Jonathan P, Bradford, Yuki, Braund, Peter S, Brody, Jennifer A, Burgdorf, Kristoffer S, Cade, Brian E, Cai, Hui, Cai, Qiuyin, Campbell, Archie, Cañadas-Garre, Marisa, Catamo, Eulalia, Chai, Jin-Fang, Chai, Xiaoran, Chang, Li-Ching, Chang, Yi-Cheng, Chen, Chien-Hsiun, Chesi, Alessandra, Choi, Seung Hoan, Chung, Ren-Hua, Cocca, Massimiliano, Concas, Maria Pina, Couture, Christian, Cuellar-Partida, Gabriel, Danning, Rebecca, Daw, E Warwick, Degenhard, Frauke, Delgado, Graciela E, Delitala, Alessandro, Demirkan, Ayse, Deng, Xuan, Devineni, Poornima, Dietl, Alexander, Dimitriou, Maria, Dimitrov, Latchezar, Dorajoo, Rajkumar, Ekici, Arif B, Engmann, Jorgen E, Fairhurst-Hunter, Zammy, Farmaki, Aliki-Eleni, Faul, Jessica D, Fernandez-Lopez, Juan-Carlo, Forer, Luka, Francescatto, Margherita, Freitag-Wolf, Sandra, Fuchsberger, Christian, Galesloot, Tessel E, Gao, Yan, Gao, Zishan, Geller, Frank, Giannakopoulou, Olga, Giulianini, Franco, Gjesing, Anette P, Goel, Anuj, Gordon, Scott D, Gorski, Mathia, Grove, Jakob, Guo, Xiuqing, Gustafsson, Stefan, Haessler, Jeffrey, Hansen, Thomas F, Havulinna, Aki S, Haworth, Simon J, He, Jing, Heard-Costa, Nancy, Hebbar, Prashantha, Hindy, George, Ho, Yuk-Lam A, Hofer, Edith, Holliday, Elizabeth, Horn, Katrin, Hornsby, Whitney E, Hottenga, Jouke-Jan, Huang, Hongyan, Huang, Jie, Huerta-Chagoya, Alicia, Huffman, Jennifer E, Hung, Yi-Jen, Huo, Shaofeng, Hwang, Mi Yeong, Iha, Hiroyuki, Ikeda, Daisuke D, Isono, Masato, Jackson, Anne U, Jäger, Susanne, Jansen, Iris E, Johansson, Ingegerd, Jonas, Jost B, Jonsson, Anna, Jørgensen, Torben, Kalafati, Ioanna-Panagiota, Kanai, Masahiro, Kanoni, Stavroula, Kårhus, Line L, Kasturiratne, Anuradhani, Katsuya, Tomohiro, Kawaguchi, Takahisa, Kember, Rachel L, Kentistou, Katherine A, Kim, Han-Na, Kim, Young Jin, Kleber, Marcus E, Knol, Maria J, Kurbasic, Azra, Lauzon, Marie, Le, Phuong, Lea, Rodney, Lee, Jong-Young, Leonard, Hampton L, Li, Shengchao A, Li, Xiaohui, Li, Xiaoyin, Liang, Jingjing, Lin, Honghuang, Lin, Shih-Yi, Liu, Jun, Liu, Xueping, Lo, Ken Sin, Long, Jirong, Lores-Motta, Laura, Luan, Jian'An, Lyssenko, Valeriya, Lyytikäinen, Leo-Pekka, Mahajan, Anubha, Mamakou, Vasiliki, Mangino, Massimo, Manichaikul, Ani, Marten, Jonathan, Mattheisen, Manuel, Mavarani, Laven, Mcdaid, Aaron F, Meidtner, Karina, Melendez, Tori L, Mercader, Josep M, Milaneschi, Yuri, Miller, Jason E, Millwood, Iona Y, Mishra, Pashupati P, Mitchell, Ruth E, Møllehave, Line T, Morgan, Anna, Mucha, Soeren, Munz, Matthia, Nakatochi, Masahiro, Nelson, Christopher P, Nethander, Maria, Nho, Chu Won, Nielsen, Aneta A, Nolte, Ilja M, Nongmaithem, Suraj S, Noordam, Raymond, Ntalla, Ioanna, Nutile, Teresa, Pandit, Anita, Christofidou, Paraskevi, Pärna, Katri, Pauper, Marc, Petersen, Eva R B, Petersen, Liselotte V, Pitkänen, Niina, Polašek, Ozren, Poveda, Alaitz, Preuss, Michael H, Pyarajan, Saiju, Raffield, Laura M, Rakugi, Hiromi, Ramirez, Julia, Rasheed, Asif, Raven, Denni, Rayner, Nigel W, Riveros, Carlo, Rohde, Rebecca, Ruggiero, Daniela, Ruotsalainen, Sanni E, Ryan, Kathleen A, Sabater-Lleal, Maria, Saxena, Richa, Scholz, Marku, Sendamarai, Anoop, Shen, Botong, Shi, Jingchunzi, Shin, Jae Hun, Sidore, Carlo, Sitlani, Colleen M, Slieker, Roderick C, Smit, Roelof A J, Smith, Albert V, Smith, Jennifer A, Smyth, Laura J, Southam, Lorraine, Steinthorsdottir, Valgerdur, Sun, Liang, Takeuchi, Fumihiko, Tallapragada, Divya Sri Priyanka, Taylor, Kent D, Tayo, Bamidele O, Tcheandjieu, Catherine, Terzikhan, Natalie, Tesolin, Paola, Teumer, Alexander, Theusch, Elizabeth, Thompson, Deborah J, Thorleifsson, Gudmar, Timmers, Paul R H J, Trompet, Stella, Turman, Constance, Vaccargiu, Simona, van der Laan, Sander W, van der Most, Peter J, van Klinken, Jan B, van Setten, Jessica, Verma, Shefali S, Verweij, Niek, Veturi, Yogasudha, Wang, Carol A, Wang, Chaolong, Wang, Lihua, Wang, Zhe, Warren, Helen R, Bin Wei, Wen, Wickremasinghe, Ananda R, Wielscher, Matthia, Wiggins, Kerri L, Winsvold, Bendik S, Wong, Andrew, Wu, Yang, Wuttke, Matthia, Xia, Rui, Xie, Tian, Yamamoto, Ken, Yang, Jingyun, Yao, Jie, Young, Hannah, Yousri, Noha A, Yu, Lei, Zeng, Lingyao, Zhang, Weihua, Zhang, Xinyuan, Zhao, Jing-Hua, Zhao, Wei, Zhou, Wei, Zimmermann, Martina E, Zoledziewska, Magdalena, Adair, Linda S, Adams, Hieab H H, Aguilar-Salinas, Carlos A, Al-Mulla, Fahd, Arnett, Donna K, Asselbergs, Folkert W, Åsvold, Bjørn Olav, Attia, John, Banas, Bernhard, Bandinelli, Stefania, Bennett, David A, Bergler, Tobia, Bharadwaj, Dwaipayan, Biino, Ginevra, Bisgaard, Han, Boerwinkle, Eric, Böger, Carsten A, Bønnelykke, Klau, Boomsma, Dorret I, Børglum, Anders D, Borja, Judith B, Bouchard, Claude, Bowden, Donald W, Brandslund, Ivan, Brumpton, Ben, Buring, Julie E, Caulfield, Mark J, Chambers, John C, Chandak, Giriraj R, Chanock, Stephen J, Chaturvedi, Nish, Chen, Yii-Der Ida, Chen, Zhengming, Cheng, Ching-Yu, Christophersen, Ingrid E, Ciullo, Marina, Cole, John W, Collins, Francis S, Cooper, Richard S, Cruz, Miguel, Cucca, Francesco, Cupples, L Adrienne, Cutler, Michael J, Damrauer, Scott M, Dantoft, Thomas M, de Borst, Gert J, de Groot, Lisette C P G M, De Jager, Philip L, de Kleijn, Dominique P V, Janaka de Silva, H, Dedoussis, George V, den Hollander, Anneke I, Du, Shufa, Easton, Douglas F, Elders, Petra J M, Eliassen, A Heather, Ellinor, Patrick T, Elmståhl, Sölve, Erdmann, Jeanette, Evans, Michele K, Fatkin, Diane, Feenstra, Bjarke, Feitosa, Mary F, Ferrucci, Luigi, Ford, Ian, Fornage, Myriam, Franke, Andre, Franks, Paul W, Freedman, Barry I, Gasparini, Paolo, Gieger, Christian, Girotto, Giorgia, Goddard, Michael E, Golightly, Yvonne M, Gonzalez-Villalpando, Clicerio, Gordon-Larsen, Penny, Grallert, Harald, Grant, Struan F A, Grarup, Niel, Griffiths, Lyn, Gudnason, Vilmundur, Haiman, Christopher, Hakonarson, Hakon, Hansen, Torben, Hartman, Catharina A, Hattersley, Andrew T, Hayward, Caroline, Heckbert, Susan R, Heng, Chew-Kiat, Hengstenberg, Christian, Hewitt, Alex W, Hishigaki, Haretsugu, Hoyng, Carel B, Huang, Paul L, Huang, Wei, Hunt, Steven C, Hveem, Kristian, Hyppönen, Elina, Iacono, William G, Ichihara, Sahoko, Ikram, M Arfan, Isasi, Carmen R, Jackson, Rebecca D, Jarvelin, Marjo-Riitta, Jin, Zi-Bing, Jöckel, Karl-Heinz, Joshi, Peter K, Jousilahti, Pekka, Jukema, J Wouter, Kähönen, Mika, Kamatani, Yoichiro, Kang, Kui Dong, Kaprio, Jaakko, Kardia, Sharon L R, Karpe, Fredrik, Kato, Norihiro, Kee, Frank, Kessler, Thorsten, Khera, Amit V, Khor, Chiea Chuen, Kiemeney, Lambertus A L M, Kim, Bong-Jo, Kim, Eung Kweon, Kim, Hyung-Lae, Kirchhof, Paulu, Kivimaki, Mika, Koh, Woon-Puay, Koistinen, Heikki A, Kolovou, Genovefa D, Kooner, Jaspal S, Kooperberg, Charle, Köttgen, Anna, Kovacs, Peter, Kraaijeveld, Adriaan, Kraft, Peter, Krauss, Ronald M, Kumari, Meena, Kutalik, Zoltan, Laakso, Markku, Lange, Leslie A, Langenberg, Claudia, Launer, Lenore J, Le Marchand, Loic, Lee, Hyejin, Lee, Nanette R, Lehtimäki, Terho, Li, Huaixing, Li, Liming, Lieb, Wolfgang, Lin, Xu, Lind, Lar, Linneberg, Allan, Liu, Ching-Ti, Liu, Jianjun, Loeffler, Marku, London, Barry, Lubitz, Steven A, Lye, Stephen J, Mackey, David A, Mägi, Reedik, Magnusson, Patrik K E, Marcus, Gregory M, Vidal, Pedro Marque, Martin, Nicholas G, März, Winfried, Matsuda, Fumihiko, Mcgarrah, Robert W, Mcgue, Matt, Mcknight, Amy Jayne, Medland, Sarah E, Mellström, Dan, Metspalu, Andre, Mitchell, Braxton D, Mitchell, Paul, Mook-Kanamori, Dennis O, Morris, Andrew D, Mucci, Lorelei A, Munroe, Patricia B, Nalls, Mike A, Nazarian, Saman, Nelson, Amanda E, Neville, Matt J, Newton-Cheh, Christopher, Nielsen, Christopher S, Nöthen, Markus M, Ohlsson, Clae, Oldehinkel, Albertine J, Orozco, Lorena, Pahkala, Katja, Pajukanta, Päivi, Palmer, Colin N A, Parra, Esteban J, Pattaro, Cristian, Pedersen, Oluf, Pennell, Craig E, Penninx, Brenda W J H, Perusse, Loui, Peters, Annette, Peyser, Patricia A, Porteous, David J, Posthuma, Danielle, Power, Chri, Pramstaller, Peter P, Province, Michael A, Qi, Qibin, Qu, Jia, Rader, Daniel J, Raitakari, Olli T, Ralhan, Sarju, Rallidis, Loukianos S, Rao, Dabeeru C, Redline, Susan, Reilly, Dermot F, Reiner, Alexander P, Rhee, Sang Youl, Ridker, Paul M, Rienstra, Michiel, Ripatti, Samuli, Ritchie, Marylyn D, Roden, Dan M, Rosendaal, Frits R, Rotter, Jerome I, Rudan, Igor, Rutters, Femke, Sabanayagam, Charumathi, Saleheen, Danish, Salomaa, Veikko, Samani, Nilesh J, Sanghera, Dharambir K, Sattar, Naveed, Schmidt, Börge, Schmidt, Helena, Schmidt, Reinhold, Schulze, Matthias B, Schunkert, Heribert, Scott, Laura J, Scott, Rodney J, Sever, Peter, Shiroma, Eric J, Shoemaker, M Benjamin, Shu, Xiao-Ou, Simonsick, Eleanor M, Sims, Mario, Singh, Jai Rup, Singleton, Andrew B, Sinner, Moritz F, Smith, J Gustav, Snieder, Harold, Spector, Tim D, Stampfer, Meir J, Stark, Klaus J, Strachan, David P, 't Hart, Leen M, Tabara, Yasuharu, Tang, Hua, Tardif, Jean-Claude, Thanaraj, Thangavel A, Timpson, Nicholas J, Tönjes, Anke, Tremblay, Angelo, Tuomi, Tiinamaija, Tuomilehto, Jaakko, Tusié-Luna, Maria-Teresa, Uitterlinden, Andre G, van Dam, Rob M, van der Harst, Pim, Van der Velde, Nathalie, van Duijn, Cornelia M, van Schoor, Natasja M, Vitart, Veronique, Völker, Uwe, Vollenweider, Peter, Völzke, Henry, Wacher-Rodarte, Niels H, Walker, Mark, Wang, Ya Xing, Wareham, Nicholas J, Watanabe, Richard M, Watkins, Hugh, Weir, David R, Werge, Thomas M, Widen, Elisabeth, Wilkens, Lynne R, Willemsen, Gonneke, Willett, Walter C, Wilson, James F, Wong, Tien-Yin, Woo, Jeong-Taek, Wright, Alan F, Wu, Jer-Yuarn, Xu, Huichun, Yajnik, Chittaranjan S, Yokota, Mitsuhiro, Yuan, Jian-Min, Zeggini, Eleftheria, Zemel, Babette S, Zheng, Wei, Zhu, Xiaofeng, Zmuda, Joseph M, Zonderman, Alan B, Zwart, John-Anker, Chasman, Daniel I, Cho, Yoon Shin, Heid, Iris M, Mccarthy, Mark I, Ng, Maggie C Y, O'Donnell, Christopher J, Rivadeneira, Fernando, Thorsteinsdottir, Unnur, Sun, Yan V, Tai, E Shyong, Boehnke, Michael, Deloukas, Pano, Justice, Anne E, Lindgren, Cecilia M, Loos, Ruth J F, Mohlke, Karen L, North, Kari E, Stefansson, Kari, Walters, Robin G, Winkler, Thomas W, Young, Kristin L, Loh, Po-Ru, Yang, Jian, Esko, Tõnu, Assimes, Themistocles L, Auton, Adam, Abecasis, Goncalo R, Willer, Cristen J, Locke, Adam E, Berndt, Sonja I, Lettre, Guillaume, Frayling, Timothy M, Okada, Yukinori, Wood, Andrew R, and Visscher, Peter M
Subjects: multi-ancestry, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Medizin, 45/43, Genome-wide association studies, Sensory disorders Donders Center for Medical Neuroscience [Radboudumc 12], Linkage Disequilibrium, Gene Frequency, RARE, IMPUTATION, PRACTICAL Consortium, GWAS, genes, ARCHITECTURE, Genome, Human/genetics, Multidisciplinary, Body Height/genetics, HERITABILITY, SCORES, article, Chromosome Mapping, 631/208/721, Polymorphism, Single Nucleotide/genetics, 3142 Public health care science, environmental and occupational health, Nutritional Biology, Europe, Phenotype, Gene Frequency/genetics, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], VA Million Veteran Program, Molecular and Laser Physics, dimorphism, blood, lipid, Medical Genetics, Single Nucleotide/genetics, genetic variant, Understanding Society Scientific Group, height, genetic, Haplotypes/genetics, 631/208/205/2138, saturated map, 23andMe Research Team, Polymorphism, Single Nucleotide, single-nucleotide polymorphisms (SNPs), Europe/ethnology, Lifelines Cohort Study, RESOURCE, UK BIOBANK, REVEALS, Life Science, DiscovEHR (DiscovEHR and MyCode Community Health Initiative), Humans, Linkage Disequilibrium/genetics, genomic regions, Polymorphism, GENOME-WIDE ASSOCIATION, gene, genetic variants, human height, 631/208/480, VLAG, Medicinsk genetik, eMERGE (Electronic Medical Records and Genomics Network), Genome, Human, Spectroscopy of Cold Molecules, Quantitative traits, Genome, Human/genetics, Genome-Wide Association Study, Sample Size, Body Height, 3141 Health care science, Haplotypes, Genetic markers, 3111 Biomedicine
Abstract: Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40-50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes(1). Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs (or all SNPs in the HapMap 3 panel(2)) account for 40% (45%) of phenotypic variance in populations of European ancestry but only around 10-20% (14-24%) in populations of other ancestries. Effect sizes, associated regions and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely to be explained by linkage disequilibrium and differences in allele frequency within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than are needed to implicate causal genes and variants. Overall, this study provides a comprehensive map of specific genomic regions that contain the vast majority of common height-associated variants. Although this map is saturated for populations of European ancestry, further research is needed to achieve equivalent saturation in other ancestries. A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.
Published: 2022

7. Genetic diversity fuels gene discovery for tobacco and alcohol use

Author: Saunders, Gretchen R. B., Wang, Xingyan, Chen, Fang, Jang, Seon-Kyeong, Liu, Mengzhen, Wang, Chen, Gao, Shuang, Jiang, Yu, Khunsriraksakul, Chachrit, Otto, Jacqueline M., Addison, Clifton, Akiyama, Masato, Albert, Christine M., Aliev, Fazil, Alonso, Alvaro, Arnett, Donna K., Ashley-Koch, Allison E., Ashrani, Aneel A., Barnes, Kathleen C., Barr, R. Graham, Bartz, Traci M., Becker, Diane M., Bielak, Lawrence F., Benjamin, Emelia J., Bis, Joshua C., Bjornsdottir, Gyda, Blangero, John, Bleecker, Eugene R., Boardman, Jason D., Boerwinkle, Eric, Boomsma, Dorret, Boorgula, Meher Preethi, Bowden, Donald W., Brody, Jennifer A., Cade, Brian E., Chasman, Daniel, Chavan, Sameer, Chen, Yii-Der Ida, Chen, Zhengming, Cheng, Iona, Cho, Michael H., Choquet, Helene, Cole, John W., Cornelis, Marilyn C., Cucca, Francesco, Curran, Joanne E., de Andrade, Mariza, Dick, Danielle M., Docherty, Anna R., Duggirala, Ravindranath, Eaton, Charles B., Ehringer, Marissa A., Esko, Tonu, Faul, Jessica D., Silva, Lilian Fernandes, Fiorillo, Edoardo, Fornage, Myriam, Freedman, Barry, Gabrielsen, Maiken E., Garrett, Melanie E., Gharib, Sina A., Gieger, Christian, Gillespie, Nathan, Glahn, David C., Gordon, Scott D., Gu, Charles C., Gu, Dongfeng, Gudbjartsson, Daniel F., Guo, Xiuqing, Haessler, Jeffrey, Hall, Michael E., Haller, Toomas, Harris, Kathleen Mullan, He, Jiang, Herd, Pamela, Hewitt, John K., Hickie, Ian, Hidalgo, Bertha, Hokanson, John E., Hopfer, Christian, Hottenga, JoukeJan, Hou, Lifang, Huang, Hongyan, Hung, Yi-Jen, Hunter, David J., Hveem, Kristian, Hwang, Shih-Jen, Hwu, Chii-Min, Iacono, William, Irvin, Marguerite R., Jee, Yon Ho, Johnson, Eric O., Joo, Yoonjung Y., Jorgenson, Eric, Justice, Anne E., Kamatani, Yoichiro, Kaplan, Robert C., Kaprio, Jaakko, Kardia, Sharon L. R., Keller, Matthew C., Kelly, Tanika N., Kooperberg, Charles, Korhonen, Tellervo, Kraft, Peter, Krauter, Kenneth, Kuusisto, Johanna, Laakso, Markku, Lasky-Su, Jessica, Lee, Wen-Jane, Lee, James J., Levy, Daniel, Li, Liming, Li, Kevin, Li, Yuqing, Lin, Kuang, Lind, Penelope A., Liu, Chunyu, Lloyd-Jones, Donald M., Lutz, Sharon M., Ma, Jiantao, Magi, Reedik, Manichaikul, Ani, Martin, Nicholas G., Mathur, Ravi, Matoba, Nana, McArdle, Patrick F., McGue, Matt, McQueen, Matthew B., Medland, Sarah E., Metspalu, Andres, Meyers, Deborah A., Millwood, Iona Y., Mitchell, Braxton D., Mohlke, Karen L., Moll, Matthew, Montasser, May E., Morrison, Alanna C., Mulas, Antonella, Nielsen, Jonas B., North, Kari E., Oelsner, Elizabeth C., Okada, Yukinori, Orru, Valeria, Palmer, Nicholette D., Palviainen, Teemu, Pandit, Anita, Park, S. Lani, Peters, Ulrike, Peters, Annette, Peyser, Patricia A., Polderman, Tinca J. C., Rafaels, Nicholas, Redline, Susan, Reed, Robert M., Reiner, Alex P., Rice, John P., Rich, Stephen S., Richmond, Nicole E., Roan, Carol, Rotter, Jerome, Rueschman, Michael N., Runarsdottir, Valgerdur, Saccone, Nancy L., Schwartz, David A., Shadyab, Aladdin H., Shi, Jingchunzi, Shringarpure, Suyash S., Sicinski, Kamil, Skogholt, Anne Heidi, Smith, Jennifer A., Smith, Nicholas L., Sotoodehnia, Nona, Stallings, Michael C., Stefansson, Hreinn, Stefansson, Kari, Stitzel, Jerry A., Sun, Xiao, Syed, Moin, Tal-Singer, Ruth, Taylor, Amy E., Taylor, Kent D., Telen, Marilyn J., Thai, Khanh K., Tiwari, Hemant, Turman, Constance, Tyrfingsson, Thorarinn, Wall, Tamara L., Walters, Robin G., Weir, David R., Weiss, Scott T., White, Wendy B., Whitfield, John B., Wiggins, Kerri L., Willemsen, Gonneke, Willer, Cristen J., Winsvold, Bendik S., Xu, Huichun, Yanek, Lisa R., Yin, Jie, Young, Kristin L., Young, Kendra A., Yu, Bing, Zhao, Wei, Zhou, Wei, Zollner, Sebastian, Zuccolo, Luisa, Project, The Biobank Japan, Batini, Chiara, Bergen, Andrew W., Bierut, Laura J., David, Sean P., Taliun, Sarah A. Gagliano, Hancock, Dana B., Jiang, Bibo, Munafo, Marcus R., Thorgeirsson, Thorgeir E., Liu, Dajiang J., Vrieze, Scott, Pediatrics, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Biological Psychology, Amsterdam Reproduction & Development, APH - Mental Health, APH - Methodology, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, Clinical Developmental Psychology, Institute for Molecular Medicine Finland, University Management, Tellervo Korhonen / Principal Investigator, Genetic Epidemiology, and University of Helsinki
Subjects: Multidisciplinary, Internationality, Protein, Genetic Predisposition to Disease/genetics, 1184 Genetics, developmental biology, physiology, Neurotrophic factors, Alcohol Drinking/genetics, Europe/ethnology, Genetic Variation/genetics, Tobacco Use/genetics, SDG 3 - Good Health and Well-being, Risk Factors, Sample Size, Genetic Loci/genetics, Genome-Wide Association Study/methods, Humans, Disease, 3111 Biomedicine, Prediction, Transcriptome, Multifactorial Inheritance/genetics, Model
Abstract: Tobacco and alcohol use are heritable behaviours associated with 15% and 5.3% of worldwide deaths, respectively, due largely to broad increased risk for disease and injury1–4. These substances are used across the globe, yet genome-wide association studies have focused largely on individuals of European ancestries5. Here we leveraged global genetic diversity across 3.4 million individuals from four major clines of global ancestry (approximately 21% non-European) to power the discovery and fine-mapping of genomic loci associated with tobacco and alcohol use, to inform function of these loci via ancestry-aware transcriptome-wide association studies, and to evaluate the genetic architecture and predictive power of polygenic risk within and across populations. We found that increases in sample size and genetic diversity improved locus identification and fine-mapping resolution, and that a large majority of the 3,823 associated variants (from 2,143 loci) showed consistent effect sizes across ancestry dimensions. However, polygenic risk scores developed in one ancestry performed poorly in others, highlighting the continued need to increase sample sizes of diverse ancestries to realize any potential benefit of polygenic prediction.
Published: 2022

8. 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

9. Cerebral small vessel disease genomics and its implications across the lifespan

Author: Sargurupremraj, Muralidharan, Suzuki, Hideaki, Zhao, Wei, Okada, Yukinori, Mazoyer, Bernard, Wardlaw, Joanna M, Nyquist, Paul A, Mather, Karen A, Grabe, Hans, Schmidt, Helena, Van Duijn, Cornelia M, Gudnason, Vilmundur, Longstreth, William T, Armstrong, Nicola J, Launer, Lenore J, Lathrop, Mark, Seshadri, Sudha, Tzourio, Christophe, Adams, Hieab H, Matthews, Paul M, Fornage, Myriam, Debette, Stéphanie, Amouyel, Philippe, de Andrade, Mariza, Hofer, Edith, Basu, Saonli, Berr, Claudine, Brody, Jennifer A, Chasman, Daniel I, Dartigues, Jean-Francois, Folsom, Aaron R, Germain, Marine, de Haan, Hugoline, Heit, John, Houwing-Duitermaat, Jeanine, Yanek, Lisa R, Kabrhel, Christopher, Kraft, Peter, Legal, Grégoire, Lindström, Sara, Monajemi, Ramin, Morange, Pierre-Emmanuel, Psaty, Bruce M, Reitsma, Pieter H, Ridker, Paul M, Rose, Lynda M, Hagenaars, Saskia P, Rosendaal, Frits R, Saut, Noémie, Slagboom, Eline, Smadja, David, Smith, Nicholas L, Suchon, Pierre, Tang, Weihong, Taylor, Kent D, Trégouët, David-Alexandre, Kumar, Rajan B, de Visser, Marieke C H, van Hylckama Vlieg, Astrid, Weng, Lu-Chen, Wiggins, Kerri L, Gormley, Padhraig, Anttila, Verneri, Winsvold, Bendik S, Palta, Priit, Esko, Tonu, Pers, Tune H, van den Akker, Erik B, Farh, Kai-How, Cuenca-Leon, Ester, Muona, Mikko, Furlotte, Nicholas A, Kurth, Tobias, Ingason, Andres, McMahon, George, Ligthart, Lannie, Terwindt, Gisela M, Kallela, Mikko, McWhirter, Rebekah E, Freilinger, Tobias M, Ran, Caroline, Gordon, Scott G, Stam, Anine H, Steinberg, Stacy, Borck, Guntram, Koiranen, Markku, Quaye, Lydia, Adams, Hieab H H, Lehtimäki, Terho, Trompet, Stella, Sarin, Antti-Pekka, Wedenoja, Juho, Hinds, David A, Buring, Julie E, Schürks, Markus, Gudlaug Hrafnsdottir, Maria, Stefansson, Hreinn, Ring, Susan M, Hottenga, Jouke-Jan, Mishra, Aniket, Penninx, Brenda W J H, Färkkilä, Markus, Artto, Ville, Kaunisto, Mari, Vepsäläinen, Salli, Malik, Rainer, Heath, Andrew C, Madden, Pamela A F, Martin, Nicholas G, Montgomery, Grant W, Jian, Xueqiu, Saba, Yasaman, Kurki, Mitja, Kals, Mart, Mägi, Reedik, Pärn, Kalle, Hämäläinen, Eija, Huang, Hailiang, Byrnes, Andrea E, Franke, Lude, Huang, Jie, Stergiakouli, Evie, Satizabal, Claudia L, Lee, Phil H, Sandor, Cynthia, Webber, Caleb, Cader, Zameel, Muller-Myhsok, Bertram, Schreiber, Stefanie, Meitinger, Thomas, Eriksson, Johan G, Salomaa, Veikko, Heikkilä, Kauko, Beaudet, Gregory, Loehrer, Elizabeth, Uitterlinden, Andre G, Hofman, Albert, van Duijn, Cornelia M, Cherkas, Lynn, Pedersen, Linda M, Stubhaug, Audun, Nielsen, Christopher S, Männikkö, Minna, Mihailov, Evelin, Petit, Laurent, Milani, Lili, Göbel, Hartmut, Esserlind, Ann-Louise, Francke Christensen, Anne, Folkmann Hansen, Thomas, Werge, Thomas, Kaprio, Jaakko, Aromaa, Arpo J, Raitakari, Olli, Ikram, M Arfan, Tsuchida, Ami, Spector, Tim, Järvelin, Marjo-Riitta, Metspalu, Andres, Kubisch, Christian, Strachan, David P, Ferrari, Michel D, Belin, Andrea C, Dichgans, Martin, Wessman, Maija, van den Maagdenberg, Arn M J M, Zago, Laure, Zwart, John-Anker, Boomsma, Dorret I, Davey Smith, George, Stefansson, Kari, Eriksson, Nicholas, Daly, Mark J, Neale, Benjamin M, Olesen, Jes, Nyholt, Dale R, Schilling, Sabrina, Palotie, Aarno, Sigurdsson, Sigurdur, Gottesman, Rebecca F, Lewis, Cora E, Sarnowski, Chloé, Aggarwal, Neelum T, Lopez, Oscar L, Smith, Jennifer A, Valdés Hernández, Maria C, van der Grond, Jeroen, Wright, Margaret J, Knol, Maria J, Dörr, Marcus, Thomson, Russell J, Bordes, Constance, Evans, Tavia E, Le Grand, Quentin, Duperron, Marie-Gabrielle, Smith, Albert V, Knopman, David S, Schreiner, Pamela J, Evans, Denis A, Rotter, Jerome I, Beiser, Alexa S, Maniega, Susana Muñoz, Beekman, Marian, Bis, Joshua C, Trollor, Julian, Stott, David J, Vernooij, Meike W, Wittfeld, Katharina, Niessen, Wiro J, Soumaré, Aicha, Boerwinkle, Eric, Sidney, Stephen, Turner, Stephen T, Davies, Gail, Eiriksdottir, Gudny, Thalamuthu, Anbupalam, Völker, Uwe, van Buchem, Mark A, Bryan, R Nick, Dupuis, Josée, Bastin, Mark E, Ames, David, Teumer, Alexander, Kwok, John B, Sakaue, Saori, Bülow, Robin, Deary, Ian J, Schofield, Peter R, Brodaty, Henry, Jiang, Jiyang, Tabara, Yasuharu, Setoh, Kazuya, Miyamoto, Susumu, Yoshida, Kazumichi, Nagata, Manabu, Terzikhan, Natalie, Kamatani, Yoichiro, Matsuda, Fumihiko, Bennett, David A, De Jager, Philip L, Mosley, Thomas H, Sachdev, Perminder S, Schmidt, Reinhold, Warren, Helen R, Evangelou, Evangelos, Habes, Mohamad, Thrombosis, International Network against, Consortium, International Headache Genomics, Ikram, Mohammad A, Wen, Wei, DeCarli, Charles, Srikanth, Velandai K, Jukema, J Wouter, Slagboom, Eline P, Kardia, Sharon L R, Equipe VINTAGE - Inserm U1219 [Bordeaux], Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Groupe d'imagerie neurofonctionnelle (GIN), Institut des Maladies Neurodégénératives [Bordeaux] (IMN), and Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)
Subjects: Adult, Male, epidemiology [Alzheimer Disease], genetics [Alzheimer Disease], diagnosis [Cerebral Small Vessel Diseases], epidemiology [Hypertension], Genome-wide association studies, behavioral disciplines and activities, Risk Assessment, Article, diagnostic imaging [White Matter], Young Adult, Alzheimer Disease, Risk Factors, White matter disease, mental disorders, Humans, Medical History Taking, Aged, Aged, 80 and over, [SCCO.NEUR]Cognitive science/Neuroscience, Mendelian Randomization Analysis, Middle Aged, White Matter, Stroke, Diffusion Tensor Imaging, Genetic Loci, Cerebral Small Vessel Diseases, complications [Cerebral Small Vessel Diseases], Hypertension, genetics [Stroke], genetics [Cerebral Small Vessel Diseases], Female, genetics [Hypertension], ddc:500, epidemiology [Stroke], Genome-Wide Association Study
Abstract: White matter hyperintensities (WMH) are the most common brain-imaging feature of cerebral small vessel disease (SVD), hypertension being the main known risk factor. Here, we identify 27 genome-wide loci for WMH-volume in a cohort of 50,970 older individuals, accounting for modification/confounding by hypertension. Aggregated WMH risk variants were associated with altered white matter integrity (p = 2.5×10-7) in brain images from 1,738 young healthy adults, providing insight into the lifetime impact of SVD genetic risk. Mendelian randomization suggested causal association of increasing WMH-volume with stroke, Alzheimer-type dementia, and of increasing blood pressure (BP) with larger WMH-volume, notably also in persons without clinical hypertension. Transcriptome-wide colocalization analyses showed association of WMH-volume with expression of 39 genes, of which four encode known drug targets. Finally, we provide insight into BP-independent biological pathways underlying SVD and suggest potential for genetic stratification of high-risk individuals and for genetically-informed prioritization of drug targets for prevention trials., White matter hyperintensities (WMH) are a common brain-imaging feature of cerebral small vessel disease. Here, the authors carry out a GWAS and followup analyses for WMH-volume, implicating several variants with potential for risk stratification and drug targeting.
Published: 2020

10. A genome-wide cross-phenotype meta-analysis of the association of blood pressure with migraine

Author: Guo, Yanjun, Rist, Pamela M., Daghlas, Iyas, Giulianini, Franco, Gormley, Padhraig, Anttila, Verneri, Winsvold, Bendik S., Palta, Priit, Esko, Tonu, Pers, Tune H., Farh, Kai How, Cuenca-Leon, Ester, Muona, Mikko, Furlotte, Nicholas A., Kurth, Tobias, Ingason, Andres, McMahon, George, Ligthart, Lannie, Terwindt, Gisela M., Kallela, Mikko, Freilinger, Tobias M., Ran, Caroline, Gordon, Scott G., Stam, Anine H., Steinberg, Stacy, Borck, Guntram, Koiranen, Markku, Quaye, Lydia, Adams, Hieab H.H., Lehtimäki, Terho, Sarin, Antti Pekka, Wedenoja, Juho, Hinds, David A., Buring, Julie E., Schürks, Markus, Ridker, Paul M., Hrafnsdottir, Maria Gudlaug, Stefansson, Hreinn, Ring, Susan M., Hottenga, Jouke Jan, Penninx, Brenda W.J.H., Färkkilä, Markus, Artto, Ville, Kaunisto, Mari, Vepsäläinen, Salli, Malik, Rainer, Heath, Andrew C., Madden, Pamela A.F., Martin, Nicholas G., Montgomery, Grant W., Kurki, Mitja, Kals, Mart, Mägi, Reedik, Pärn, Kalle, Hämäläinen, Eija, Huang, Hailiang, Byrnes, Andrea E., Franke, Lude, Huang, Jie, Stergiakouli, Evie, Lee, Phil H., Sandor, Cynthia, Webber, Caleb, Cader, Zameel, Muller-Myhsok, Bertram, Schreiber, Stefan, Meitinger, Thomas, Eriksson, Johan G., Salomaa, Veikko, Heikkilä, Kauko, Loehrer, Elizabeth, Uitterlinden, Andre G., Hofman, Albert, Duijn, Cornelia M.van, Cherkas, Lynn, Pedersen, Linda M., Stubhaug, Audun, Nielsen, Christopher S., Männikkö, Minna, Mihailov, Evelin, Milani, Lili, Göbel, Hartmut, Esserlind, Ann Louise, Christensen, Anne Francke, Hansen, Thomas Folkmann, Werge, Thomas, Kaprio, Jaakko, Aromaa, Arpo J., Raitakari, Olli, Ikram, M. Arfan, Spector, Tim, Järvelin, Marjo Riitta, Metspalu, Andres, Kubisch, Christian, Strachan, David P., Ferrari, Michel D., Belin, Andrea C., Dichgans, Martin, Wessman, Maija, Maagdenberg, Arn M.J.M.van den, Zwart, John Anker, Boomsma, Dorret I., Smith, George Davey, Stefansson, Kari, Eriksson, Nicholas, Daly, Mark J., Neale, Benjamin M., Olesen, Jes, Chasman, Daniel I., Nyholt, Dale R., Palotie, Aarno, Agee, Michelle, Auton, Adam, Bell, Robert K., Bryc, Katarzyna, Elson, Sarah L., Fontanillas, Pierre, Huber, Karen E., Kleinman, Aaron, Litterman, Nadia K., McCreight, Jennifer C., McIntyre, Matthew H., Mountain, Joanna L., Noblin, Elizabeth S., Northover, Carrie A.M., Pitts, Steven J., Sathirapongsasuti, J. Fah, Sazonova, Olga V., Shelton, Janie F., Shringarpure, Suyash, Tian, Chao, Tung, Joyce Y., Vacic, Vladimir, Læknadeild (HÍ), Faculty of Medicine (UI), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Háskóli Íslands, University of Iceland, APH - Mental Health, Amsterdam Neuroscience - Complex Trait Genetics, Psychiatry, APH - Digital Health, Radiology & Nuclear Medicine, Epidemiology, Neurology, Internal Medicine, Biological Psychology, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases, APH - Methodology, Clinicum, Neurologian yksikkö, HUS Neurocenter, HUS Helsinki and Uusimaa Hospital District, Department of Neurosciences, Research Programs Unit, Institute for Molecular Medicine Finland, Neuroscience Center, STEMM - Stem Cells and Metabolism Research Program, Genomics of Neurological and Neuropsychiatric Disorders, Department of Public Health, Biosciences, Centre of Excellence in Complex Disease Genetics, Research Programme of Molecular Medicine, Aarno Palotie / Principal Investigator, Helsinki University Hospital Area, University of Helsinki, Johan Eriksson / Principal Investigator, and Department of General Practice and Primary Health Care
Subjects: 0301 basic medicine, Netherlands Twin Register (NTR), Integrin beta Chains, LOCI, Medizin, General Physics and Astronomy, Blood Pressure, Genome-wide association study, Genome-wide association studies, DISEASE, 3124 Neurology and psychiatry, 0302 clinical medicine, HEADACHE, Risk Factors, Polymorphism (computer science), Genome-wide, lcsh:Science, Telomerase, Multidisciplinary, Mendelian Randomization Analysis, Blóðþrýstingur, 3. Good health, Pulse pressure, Mígreni, Hypertension, Blood pressure, Cross-phenotype, Erfðarannsóknir, medicine.medical_specialty, Migraine Disorders, Science, Diastole, Polymorphism, Single Nucleotide, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Meta-Analysis as Topic, SDG 3 - Good Health and Well-being, Receptors, Adrenergic, alpha-2, Internal medicine, Mendelian randomization, medicine, Humans, Genetic Predisposition to Disease, Migraine, business.industry, Proteins, General Chemistry, medicine.disease, Meta-analysis, 030104 developmental biology, Endocrinology, RISK-FACTORS, lcsh:Q, business, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: Publisher's version (útgefin grein), Blood pressure (BP) was inconsistently associated with migraine and the mechanisms of BP-lowering medications in migraine prophylaxis are unknown. Leveraging large-scale summary statistics for migraine (Ncases/Ncontrols = 59,674/316,078) and BP (N = 757,601), we find positive genetic correlations of migraine with diastolic BP (DBP, rg = 0.11, P = 3.56 × 10−06) and systolic BP (SBP, rg = 0.06, P = 0.01), but not pulse pressure (PP, rg = −0.01, P = 0.75). Cross-trait meta-analysis reveals 14 shared loci (P ≤ 5 × 10−08), nine of which replicate (P, This research has been conducted using the UK Biobank Resource under Application Number 29273. We would like to thank the participants and researchers from the UK Biobank, 23andMe, Inc., International Headache Genetics Consortium (IHGC), MEGASTROKE, CARDIoGRAM, and International Consortium of Blood Pressure-Genome Wide Association Studies (ICBP) who contributed or collected data. Daniel I. Chasman is funded by US National Institutes of Health and US National Institute of Neurological Disorders and Stroke (R21NS09296 and R21NS104398). Pamela M. Rist is funded by K01 HL128791. The MEGASTROKE project received funding from sources specified at http://www.megastroke.org/acknowledgments.html.
Published: 2020

11. Molecular genetic overlap between migraine and major depressive disorder

Author: Yang, Yuanhao, Zhao, Huiying, Boomsma, Dorret I, Smith, George Davey, Esko, Tonu, Hansen, Thomas Folkmann, Ikram, M. Arfan, Paraskevi, Christofidou, Strachan, David P., Wessman, Maija, Gormley, Padhraig, Anttila, Verneri, Winsvold, Bendik S., Palta, Priit, Pers, Tune H., Farh, Kai-How, Cuenca-Leon, Ester, Muona, Mikko, Furlotte, Nicholas A., Kurth, Tobias, Ingason, Andres, McMahon, George, Ligthart, Lannie, Kallela, Mikko, Freilinger, Tobias M., Ran, Caroline, Gordon, Scott G., Stam, Anine H., Steinberg, Stacy, Borck, Guntram, Koiranen, Markku, Quaye, Lydia, Adams, Hieab H. H., Lehtimäki, Terho, Sarin, Antti-Pekka, Wedenoja, Juho, Hinds, David A., Buring, Julie E., Schürks, Markus, Ridker, Paul M., Hrafnsdottir, Maria Gudlaug, Stefansson, Hreinn, Ring, Susan M., Hottenga, Jouke-Jan, Penninx, Brenda W. J. H., Färkkilä, Markus, Artto, Ville, Kaunisto, Mari, Vepsäläinen, Salli, Malik, Rainer, Heath, Andrew C., Madden, Pamela A. F., Martin, Nicholas G., Montgomery, Grant W, Kurki, Mitja I, Kals, Mart, Mägi, Reedik, Pärn, Kalle, Hämäläinen, Eija, Huang, Hailiang, Byrnes, Andrea E., Franke, Lude, Huang, Jie, Stergiakouli, Evie, Lee, Phil H., Sandor, Cynthia, Webber, Caleb, Cader, Zameel, Muller-Myhsok, Bertram, Schreiber, Stefan, Meitinger, Thomas, Eriksson, Johan G., Salomaa, Veikko, Heikkilä, Kauko, Loehrer, Elizabeth, Uitterlinden, Andre G., Hofman, Albert, van Duijn, Cornelia M., Cherkas, Lynn, Pedersen, Linda M., Stubhaug, Audun, Nielsen, Christopher S., Männikkö, Minna, Mihailov, Evelin, Milani, Lili, Göbel, Hartmut, Esserlind, Ann-Louise, Christensen, Anne Francke, Werge, Thomas, Kaprio, Jaakko, Aromaa, Arpo J., Raitakari, Olli, Spector, Tim, Järvelin, Marjo-Riitta, Metspalu, Andres, Kubisch, Christian, Ferrari, Michel D., Belin, Andrea C., Dichgans, Martin, Zwart, John-Anker, Stefansson, Kari, Eriksson, Nicholas, Daly, Mark J., Neale, Benjamin M., Olesen, Jes, Chasman, Daniel I., Nyholt, Dale R., Palotie, Aarno, van den Maagdenberg, Arn M. J. M., Terwindt, Gisela M., Psychiatry, APH - Mental Health, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Digital Health, Epidemiology, Biological Psychology, APH - Methodology, APH - Personalized Medicine, and APH - Health Behaviors & Chronic Diseases
Subjects: 0301 basic medicine, Netherlands Twin Register (NTR), Linkage disequilibrium, Migraine Disorders, Medizin, Single-nucleotide polymorphism, Genome-wide association study, Polymorphism, Single Nucleotide, Article, Linkage Disequilibrium, 03 medical and health sciences, 0302 clinical medicine, Potassium Channels, Tandem Pore Domain, SDG 3 - Good Health and Well-being, Genotype, Databases, Genetic, Genetics, medicine, SNP, Humans, Genetics (clinical), Depressive Disorder, Major, business.industry, medicine.disease, Comorbidity, Ankyrin Repeat, 030104 developmental biology, Migraine, Major depressive disorder, business, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: Migraine and major depressive disorder (MDD) are common brain disorders that frequently co-occur. Despite epidemiological evidence that migraine and MDD share a genetic basis, their overlap at the molecular genetic level has not been thoroughly investigated. Using single-nucleotide polymorphism (SNP) and gene-based analysis of genome-wide association study (GWAS) genotype data, we found significant genetic overlap across the two disorders. LD Score regression revealed a significant SNP-based heritability for both migraine (h2= 12%) and MDD (h2= 19%), and a significant cross-disorder genetic correlation (rG= 0.25; P = 0.04). Meta-analysis of results for 8,045,569 SNPs from a migraine GWAS (comprising 30,465 migraine cases and 143,147 control samples) and the top 10,000 SNPs from a MDD GWAS (comprising 75,607 MDD cases and 231,747 healthy controls), implicated three SNPs (rs146377178, rs672931, and rs11858956) with novel genome-wide significant association (PSNP≤ 5 × 10−8) to migraine and MDD. Moreover, gene-based association analyses revealed significant enrichment of genes nominally associated (Pgene-based≤ 0.05) with both migraine and MDD (Pbinomial-test= 0.001). Combining results across migraine and MDD, two genes, ANKDD1B and KCNK5, produced Fisher’s combined gene-based P values that surpassed the genome-wide significance threshold (PFisher’s-combined≤ 3.6 × 10−6). Pathway analysis of genes with PFisher’s-combined≤ 1 × 10−3suggested several pathways, foremost neural-related pathways of signalling and ion channel regulation, to be involved in migraine and MDD aetiology. In conclusion, our study provides strong molecular genetic support for shared genetically determined biological mechanisms underlying migraine and MDD.
Published: 2018

12. Shared genetic risk between migraine and coronary artery disease:A genome-wide analysis of common variants

Author: Winsvold, Bendik S., Bettella, Francesco, Witoelar, Aree, Anttila, Verneri, Gormley, Padhraig, Kurth, Tobias, Terwindt, Gisela M., Freilinger, Tobias, Frei, Oleksander, Shadrin, Alexey, Wang, Yunpeng, Dale, Anders M., van den Maagdenberg, Arn M.J.M., Nyholt, Dale R., Palotie, Aarno, Andreassen, Ole A., Zwart, John Anker, Artto, Ville, Belin, Andrea Carmine, Boomsma, Dorret I., Børte, Sigrid, Chasman, Daniel I., Cherkas, Lynn, Christensen, Anne Francke, Cormand, Bru, Cuenca-Leon, Ester, Davey-Smith, George, Dichgans, Martin, van Duijn, Cornelia, Eising, Else, Esko, Tonu, Esserlind, Ann Louise, Ferrari, Michel, Frants, Rune R., Furlotte, Nick, Griffiths, Lyn, Hamalainen, Eija, Hansen, Thomas Folkmann, Hiekkala, Marjo, Arfan Ikram, M., Ingason, Andres, Järvelin, Marjo Riitta, Kajanne, Risto, Kallela, Mikko, Kaprio, Jaakko, Kaunisto, Mari, Kubisch, Christian, Kurki, Mitja, Olesen, Jes, and Yao, Yong-Gang
Subjects: 0301 basic medicine, Male, Epidemiology, Genome-wide association study, Disease, Coronary Artery Disease, Pathology and Laboratory Medicine, Bioinformatics, Cardiovascular, Vascular Medicine, Migraines, Medicine and Health Sciences, Coronary Heart Disease, 2.1 Biological and endogenous factors, Aetiology, Genetics, Multidisciplinary, Headaches, Pain Research, International Headache Genetics Consortium, Genomics, Single Nucleotide, Phenotype, Heart Disease, Genetic Epidemiology, Medicine, Medical genetics, Female, Pathogens, Chronic Pain, Research Article, Biotechnology, medicine.medical_specialty, General Science & Technology, Science, Migraine Disorders, Cardiology, Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, Molecular Genetics, 03 medical and health sciences, Signs and Symptoms, Diagnostic Medicine, Clinical Research, Genome-Wide Association Studies, medicine, SNP, Humans, Genetic Predisposition to Disease, Polymorphism, Molecular Biology, Migraine, Heart Disease - Coronary Heart Disease, Genetic association, Clinical Genetics, Prevention, Human Genome, Biology and Life Sciences, Computational Biology, Human Genetics, Genome Analysis, medicine.disease, Atherosclerosis, Brain Disorders, 030104 developmental biology, Genetic epidemiology, Genetic Loci, Genome-Wide Association Study
Abstract: Migraine is a recurrent pain condition traditionally viewed as a neurovascular disorder, but little is known of its vascular basis. In epidemiological studies migraine is associated with an increased risk of cardiovascular disease, including coronary artery disease (CAD), suggesting shared pathogenic mechanisms. This study aimed to determine the genetic overlap between migraine and CAD, and to identify shared genetic risk loci, utilizing a conditional false discovery rate approach and data from two large-scale genome-wide association studies (GWAS) of CAD (C4D, 15,420 cases, 15,062 controls; CARDIoGRAM, 22,233 cases, 64,762 controls) and one of migraine (22,120 cases, 91,284 controls). We found significant enrichment of genetic variants associated with CAD as a function of their association with migraine, which was replicated across two independent CAD GWAS studies. One shared risk locus in the PHACTR1 gene (conjunctional false discovery rate for index SNP rs9349379 < 3.90 x 10−5), which was also identified in previous studies, explained much of the enrichment. Two further loci (in KCNK5 and AS3MT) showed evidence for shared risk (conjunctional false discovery rate < 0.05). The index SNPs at two of the three loci had opposite effect directions in migraine and CAD. Our results confirm previous reports that migraine and CAD share genetic risk loci in excess of what would be expected by chance, and highlight one shared risk locus in PHACTR1. Understanding the biological mechanisms underpinning this shared risk is likely to improve our understanding of both disorders. © 2017 Winsvold et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Published: 2017

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

Author: Mark K. Bakker, Jos P. Kanning, Gad Abraham, Amy E. Martinsen, Bendik S. Winsvold, John-Anker Zwart, Romain Bourcier, Tomonobu Sawada, Masaru Koido, Yoichiro Kamatani, Sandrine Morel, Philippe Amouyel, Stéphanie Debette, Philippe Bijlenga, Takiy Berrandou, Santhi K. Ganesh, Nabila Bouatia-Naji, Gregory Jones, Matthew Bown, Gabriel J.E. Rinkel, Jan H. Veldink, Ynte M. Ruigrok, Anne Hege Aamodt, Anne Heidi Skogholt, Ben M Brumpton, Cristen J Willer, Else C Sandset, Espen S Kristoffersen, Hanne Ellekjær, Ingrid Heuch, Jonas B Nielsen, Knut Hagen, Kristian Hveem, Lars G Fritsche, Laurent F Thomas, Linda M Pedersen, Maiken E Gabrielsen, Oddgeir L Holmen, Sigrid Børte, Wei Zhou, Shérine Abboud, Massimo Pandolfo, Vincent Thijs, Didier Leys, Marie Bodenant, Fabien Louillet, Emmanuel Touzé, Jean-Louis Mas, Yves Samson, Sara Leder, Anne Léger, Sandrine Deltour, Sophie Crozier, Isabelle Méresse, Sandrine Canaple, Olivier Godefroy, Maurice Giroud, Yannick Béjot, Pierre Decavel, Elizabeth Medeiros, Paola Montiel, Thierry Moulin, Fabrice Vuillier, Jean Dallongeville, Antti J Metso, Tiina Metso, Turgut Tatlisumak, Caspar Grond-Ginsbach, Christoph Lichy, Manja Kloss, Inge Werner, Marie-Luise Arnold, Michael Dos Santos, Armin Grau, Martin Dichgans, Constanze Thomas-Feles, Ralf Weber, Tobias Brandt, Alessandro Pezzini, Valeria De Giuli, Filomena Caria, Loris Poli, Alessandro Padovani, Anna Bersano, Silvia Lanfranconi, Simone Beretta, Carlo Ferrarese, Giacomo Giacolone, Stefano Paolucci, Philippe Lyrer, Stefan Engelter, Felix Fluri, Florian Hatz, Dominique Gisler, Leo Bonati, Henrik Gensicke, Margareth Amort, Hugh Markus, Jennifer Majersik, Bradford Worrall, Andrew Southerland, John Cole, Steven Kittner, Evangelos Evangelou, Helen R Warren, He Gao, Georgios Ntritsos, Niki Dimou, Tonu Esko, Reedik Mägi, Lili Milani, Peter Almgren, Thibaud Boutin, Jun Ding, Franco Giulianini, Elizabeth G Holliday, Anne U Jackson, Ruifang Li-Gao, Wei-Yu Lin, Jian’an Luan, Massimo Mangino, Christopher Oldmeadow, Bram Peter Prins, Yong Qian, Muralidharan Sargurupremraj, Nabi Shah, Praveen Surendran, Sébastien Thériault, Niek Verweij, Sara M Willems, Jing-Hua Zhao, John Connell, Renée de Mutsert, Alex SF Doney, Martin Farrall, Cristina Menni, Andrew D Morris, Raymond Noordam, Guillaume Paré, Neil R Poulter, Denis C Shields, Alice Stanton, Simon Thom, Gonçalo Abecasis, Najaf Amin, Dan E Arking, Kristin L Ayers, Caterina M Barbieri, Chiara Batini, Joshua C Bis, Tineka Blake, Murielle Bochud, Michael Boehnke, Eric Boerwinkle, Dorret I Boomsma, Erwin P Bottinger, Peter S Braund, Marco Brumat, Archie Campbell, Harry Campbell, Aravinda Chakravarti, John C Chambers, Ganesh Chauhan, Marina Ciullo, Massimiliano Cocca, Francis Collins, Heather J Cordell, Gail Davies, Martin H de Borst, Eco J de Geus, Ian J Deary, Joris Deelen, Fabiola Del Greco M, Cumhur Yusuf Demirkale, Marcus Dörr, Georg B Ehret, Roberto Elosua, Stefan Enroth, A Mesut Erzurumluoglu, Teresa Ferreira, Mattias Frånberg, Oscar H Franco, Ilaria Gandin, Paolo Gasparini, Vilmantas Giedraitis, Christian Gieger, Giorgia Girotto, Anuj Goel, Alan J Gow, Vilmundur Gudnason, Xiuqing Guo, Ulf Gyllensten, Anders Hamsten, Tamara B Harris, Sarah E Harris, Catharina A Hartman, Aki S Havulinna, Andrew A Hicks, Edith Hofer, Albert Hofman, Jouke-Jan Hottenga, Jennifer E Huffman, Shih-Jen Hwang, Erik Ingelsson, Alan James, Rick Jansen, Marjo-Riitta Jarvelin, Roby Joehanes, Åsa Johansson, Andrew D Johnson, Peter K Joshi, Pekka Jousilahti, J Wouter Jukema, Antti Jula, Mika Kähönen, Sekar Kathiresan, Bernard D Keavney, Kay-Tee Khaw, Paul Knekt, Joanne Knight, Ivana Kolcic, Jaspal S Kooner, Seppo Koskinen, Kati Kristiansson, Zoltan Kutalik, Maris Laan, Marty Larson, Lenore J Launer, Benjamin Lehne, Terho Lehtimäki, David CM Liewald, Li Lin, Lars Lind, Cecilia M Lindgren, YongMei Liu, Ruth JF Loos, Lorna M Lopez, Yingchang Lu, Leo-Pekka Lyytikäinen, Anubha Mahajan, Chrysovalanto Mamasoula, Jaume Marrugat, Jonathan Marten, Yuri Milaneschi, Anna Morgan, Andrew P Morris, Alanna C Morrison, Peter J Munson, Mike A Nalls, Priyanka Nandakumar, Christopher P Nelson, Teemu Niiranen, Ilja M Nolte, Teresa Nutile, Albertine J Oldehinkel, Ben A Oostra, Paul F O’Reilly, Elin Org, Sandosh Padmanabhan, Walter Palmas, Aarno Palotie, Alison Pattie, Brenda WJH Penninx, Markus Perola, Annette Peters, Ozren Polasek, Peter P Pramstaller, Quang Tri Nguyen, Olli T Raitakari, Rainer Rettig, Kenneth Rice, Paul M Ridker, Janina S Ried, Harriëtte Riese, Samuli Ripatti, Antonietta Robino, Lynda M Rose, Jerome I Rotter, Igor Rudan, Daniela Ruggiero, Yasaman Saba, Cinzia F Sala, Veikko Salomaa, Nilesh J Samani, Antti-Pekka Sarin, Reinhold Schmidt, Helena Schmidt, Nick Shrine, David Siscovick, Albert V Smith, Harold Snieder, Siim Sõber, Rossella Sorice, John M Starr, David J Stott, David P Strachan, Rona J Strawbridge, Johan Sundström, Morris A Swertz, Kent D Taylor, Alexander Teumer, Martin D Tobin, Maciej Tomaszewski, Daniela Toniolo, Michela Traglia, Stella Trompet, Jaakko Tuomilehto, Christophe Tzourio, André G Uitterlinden, Ahmad Vaez, Peter J van der Most, Cornelia M van Duijn, Germaine C Verwoert, Veronique Vitart, Uwe Völker, Peter Vollenweider, Dragana Vuckovic, Hugh Watkins, Sarah H Wild, Gonneke Willemsen, James F Wilson, Alan F Wright, Jie Yao, Tatijana Zemunik, Weihua Zhang, John R Attia, Adam S Butterworth, Daniel I Chasman, David Conen, Francesco Cucca, John Danesh, Caroline Hayward, Joanna MM Howson, Markku Laakso, Edward G Lakatta, Claudia Langenberg, Olle Melander, Dennis O Mook-Kanamori, Colin NA Palmer, Lorenz Risch, Robert A Scott, Rodney J Scott, Peter Sever, Tim D Spector, Pim van der Harst, Nicholas J Wareham, Eleftheria Zeggini, Daniel Levy, Patricia B Munroe, Christopher Newton-Cheh, Morris J Brown, Andres Metspalu, Bruce M. Psaty, Louise V Wain, Paul Elliott, Mark J Caulfield, Padhraig Gormley, Verneri Anttila, Priit Palta, Tune H Pers, Kai-How Farh, Ester Cuenca-Leon, Mikko Muona, Nicholas A Furlotte, Tobias Kurth, Andres Ingason, George McMahon, Lannie Ligthart, Gisela M Terwindt, Mikko Kallela, Tobias M Freilinger, Caroline Ran, Scott G Gordon, Anine H Stam, Stacy Steinberg, Guntram Borck, Markku Koiranen, Lydia Quaye, Hieab H H Adams, Juho Wedenoja, David A Hinds, Julie E Buring, Markus Schürks, Maria Gudlaug Hrafnsdottir, Hreinn Stefansson, Susan M Ring, Brenda W J H Penninx, Markus Färkkilä, Ville Artto, Mari Kaunisto, Salli Vepsäläinen, Rainer Malik, Andrew C Heath, Pamela A F Madden, Nicholas G Martin, Grant W Montgomery, Mitja I Kurki, Mart Kals, Kalle Pärn, Eija Hämäläinen, Hailiang Huang, Andrea E Byrnes, Lude Franke, Jie Huang, Evie Stergiakouli, Phil H Lee, Cynthia Sandor, Caleb Webber, Zameel Cader, Bertram Muller-Myhsok, Stefan Schreiber, Thomas Meitinger, Johan G Eriksson, Kauko Heikkilä, Elizabeth Loehrer, Andre G Uitterlinden, Lynn Cherkas, Audun Stubhaug, Christopher S Nielsen, Minna Männikkö, Evelin Mihailov, Hartmut Göbel, Ann-Louise Esserlind, Anne Francke Christensen, Thomas Folkmann Hansen, Thomas Werge, Jaakko Kaprio, Arpo J Aromaa, Olli Raitakari, M Arfan Ikram, Tim Spector, Marjo-Riitta Järvelin, Christian Kubisch, Michel D Ferrari, Andrea C Belin, Maija Wessman, Arn M J M van den Maagdenberg, George Davey Smith, Kari Stefansson, Nicholas Eriksson, Mark J Daly, Benjamin M Neale, Jes Olesen, Dale R Nyholt, Masato Akiyama, Varinder S. Alg, Joseph P. Broderick, Ben M. Brumpton, Jérôme Dauvillier, Hubert Desal, Christian Dina, Christoph M. Friedrich, Emília I. Gaál-Paavola, Jean-Christophe Gentric, Sven Hirsch, Isabel C. Hostettler, Henry Houlden, Juha E. Jääskeläinen, Marianne Bakke Johnsen, Liming Li, Kuang Lin, Antti Lindgren, Olivier Martin, Koichi Matsuda, Iona Y. Millwood, Olivier Naggara, Mika Niemelä, Joanna Pera, Richard Redon, Guy A. Rouleau, Marie Søfteland Sandvei, Sabine Schilling, Eimad Shotar, Agnieszka Slowik, Chikashi Terao, W. M. Monique Verschuren, Robin G. Walters, David J. Werring, Cristen J. Willer, Daniel Woo, Bradford B. Worrall, Sirui Zhou, Biological Psychology, Amsterdam Reproduction & Development, APH - Mental Health, APH - Methodology, AMS - Sports, AMS - Ageing & Vitality, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases, Systems Ecology, Sociology and Social Gerontology, Bakker, Mark K., Kanning, Jos P., Abraham, Gad, Martinsen, Amy E., Winsvold, Bendik S., Zwart, John-Anker, Bourcier, Romain, Sawada, Tomonobu, Koido, Masaru, Kamatani, Yoichiro, Morel, Sandrine, Amouyel, Philippe, Debette, Stéphanie, Bijlenga, Philippe, Berrandou, Takiy, Ganesh, Santhi K., Bouatia-Naji, Nabila, Jones, Gregory, Bown, Matthew, Rinkel, Gabriel J. E., Veldink, Jan H., Ruigrok, Ynte M., Girotto, G., All-In Stroke, Hunt, Group, Cadisp, Consortium for Blood Pressure, International, Headache Genetics Consortium, International, Stroke Genetics Consortium (ISGC) Intracranial Aneurysm Working Group, International, Utrecht University [Utrecht], Baker Heart and Diabetes Institute (AUSTRALIA), University of Melbourne, University of Oslo (UiO), Norwegian University of Science and Technology (NTNU), Oslo University Hospital [Oslo], Centre hospitalier universitaire de Nantes (CHU Nantes), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), The University of Tokyo (UTokyo), RIKEN Center for Integrative Medical Sciences [Yokohama] (RIKEN IMS), RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), Hôpital Universitaire de Genève = University Hospitals of Geneva (HUG), Université de Genève = University of Geneva (UNIGE), Excellence Laboratory LabEx DISTALZ, Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), University of Michigan Medical School [Ann Arbor], University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, University of Otago [Dunedin, Nouvelle-Zélande], University of Leicester, Laboratoire de Neurosciences Fonctionnelles et Pathologies - UR UPJV 4559 (LNFP), Université de Picardie Jules Verne (UPJV), CHU Amiens-Picardie, HUNT All-In Stroke, CADISP group, International Consortium for Blood Pressure, International Headache Genetics Consortium, International Stroke Genetics Consortium (ISGC) Intracranial Aneurysm Working Group: Anne Hege Aamodt, Anne Heidi Skogholt, Ben M Brumpton, Cristen J Willer, Else C Sandset, Espen S Kristoffersen, Hanne Ellekjær, Ingrid Heuch, Jonas B Nielsen, Knut Hagen, Kristian Hveem, Lars G Fritsche, Laurent F Thomas, Linda M Pedersen, Maiken E Gabrielsen, Oddgeir L Holmen, Sigrid Børte, Wei Zhou, Shérine Abboud, Massimo Pandolfo, Vincent Thijs, Didier Leys, Marie Bodenant, Fabien Louillet, Emmanuel Touzé, Jean-Louis Mas, Yves Samson, Sara Leder, Anne Léger, Sandrine Deltour, Sophie Crozier, Isabelle Méresse, Sandrine Canaple, Olivier Godefroy, Maurice Giroud, Yannick Béjot, Pierre Decavel, Elizabeth Medeiros, Paola Montiel, Thierry Moulin, Fabrice Vuillier, Jean Dallongeville, Antti J Metso, Tiina Metso, Turgut Tatlisumak, Caspar Grond-Ginsbach, Christoph Lichy, Manja Kloss, Inge Werner, Marie-Luise Arnold, Michael Dos Santos, Armin Grau, Martin Dichgans, Constanze Thomas-Feles, Ralf Weber, Tobias Brandt, Alessandro Pezzini, Valeria De Giuli, Filomena Caria, Loris Poli, Alessandro Padovani, Anna Bersano, Silvia Lanfranconi, Simone Beretta, Carlo Ferrarese, Giacomo Giacolone, Stefano Paolucci, Philippe Lyrer, Stefan Engelter, Felix Fluri, Florian Hatz, Dominique Gisler, Leo Bonati, Henrik Gensicke, Margareth Amort, Hugh Markus, Jennifer Majersik, Bradford Worrall, Andrew Southerland, John Cole, Steven Kittner, Evangelos Evangelou, Helen R Warren, He Gao, Georgios Ntritsos, Niki Dimou, Tonu Esko, Reedik Mägi, Lili Milani, Peter Almgren, Thibaud Boutin, Jun Ding, Franco Giulianini, Elizabeth G Holliday, Anne U Jackson, Ruifang Li-Gao, Wei-Yu Lin, Jian'an Luan, Massimo Mangino, Christopher Oldmeadow, Bram Peter Prins, Yong Qian, Muralidharan Sargurupremraj, Nabi Shah, Praveen Surendran, Sébastien Thériault, Niek Verweij, Sara M Willems, Jing-Hua Zhao, John Connell, Renée de Mutsert, Alex Sf Doney, Martin Farrall, Cristina Menni, Andrew D Morris, Raymond Noordam, Guillaume Paré, Neil R Poulter, Denis C Shields, Alice Stanton, Simon Thom, Gonçalo Abecasis, Najaf Amin, Dan E Arking, Kristin L Ayers, Caterina M Barbieri, Chiara Batini, Joshua C Bis, Tineka Blake, Murielle Bochud, Michael Boehnke, Eric Boerwinkle, Dorret I Boomsma, Erwin P Bottinger, Peter S Braund, Marco Brumat, Archie Campbell, Harry Campbell, Aravinda Chakravarti, John C Chambers, Ganesh Chauhan, Marina Ciullo, Massimiliano Cocca, Francis Collins, Heather J Cordell, Gail Davies, Martin H de Borst, Eco J de Geus, Ian J Deary, Joris Deelen, Fabiola Del Greco M, Cumhur Yusuf Demirkale, Marcus Dörr, Georg B Ehret, Roberto Elosua, Stefan Enroth, A Mesut Erzurumluoglu, Teresa Ferreira, Mattias Frånberg, Oscar H Franco, Ilaria Gandin, Paolo Gasparini, Vilmantas Giedraitis, Christian Gieger, Giorgia Girotto, Anuj Goel, Alan J Gow, Vilmundur Gudnason, Xiuqing Guo, Ulf Gyllensten, Anders Hamsten, Tamara B Harris, Sarah E Harris, Catharina A Hartman, Aki S Havulinna, Andrew A Hicks, Edith Hofer, Albert Hofman, Jouke-Jan Hottenga, Jennifer E Huffman, Shih-Jen Hwang, Erik Ingelsson, Alan James, Rick Jansen, Marjo-Riitta Jarvelin, Roby Joehanes, Åsa Johansson, Andrew D Johnson, Peter K Joshi, Pekka Jousilahti, J Wouter Jukema, Antti Jula, Mika Kähönen, Sekar Kathiresan, Bernard D Keavney, Kay-Tee Khaw, Paul Knekt, Joanne Knight, Ivana Kolcic, Jaspal S Kooner, Seppo Koskinen, Kati Kristiansson, Zoltan Kutalik, Maris Laan, Marty Larson, Lenore J Launer, Benjamin Lehne, Terho Lehtimäki, David Cm Liewald, Li Lin, Lars Lind, Cecilia M Lindgren, YongMei Liu, Ruth Jf Loos, Lorna M Lopez, Yingchang Lu, Leo-Pekka Lyytikäinen, Anubha Mahajan, Chrysovalanto Mamasoula, Jaume Marrugat, Jonathan Marten, Yuri Milaneschi, Anna Morgan, Andrew P Morris, Alanna C Morrison, Peter J Munson, Mike A Nalls, Priyanka Nandakumar, Christopher P Nelson, Teemu Niiranen, Ilja M Nolte, Teresa Nutile, Albertine J Oldehinkel, Ben A Oostra, Paul F O'Reilly, Elin Org, Sandosh Padmanabhan, Walter Palmas, Aarno Palotie, Alison Pattie, Brenda Wjh Penninx, Markus Perola, Annette Peters, Ozren Polasek, Peter P Pramstaller, Quang Tri Nguyen, Olli T Raitakari, Rainer Rettig, Kenneth Rice, Paul M Ridker, Janina S Ried, Harriëtte Riese, Samuli Ripatti, Antonietta Robino, Lynda M Rose, Jerome I Rotter, Igor Rudan, Daniela Ruggiero, Yasaman Saba, Cinzia F Sala, Veikko Salomaa, Nilesh J Samani, Antti-Pekka Sarin, Reinhold Schmidt, Helena Schmidt, Nick Shrine, David Siscovick, Albert V Smith, Harold Snieder, Siim Sõber, Rossella Sorice, John M Starr, David J Stott, David P Strachan, Rona J Strawbridge, Johan Sundström, Morris A Swertz, Kent D Taylor, Alexander Teumer, Martin D Tobin, Maciej Tomaszewski, Daniela Toniolo, Michela Traglia, Stella Trompet, Jaakko Tuomilehto, Christophe Tzourio, André G Uitterlinden, Ahmad Vaez, Peter J van der Most, Cornelia M van Duijn, Germaine C Verwoert, Veronique Vitart, Uwe Völker, Peter Vollenweider, Dragana Vuckovic, Hugh Watkins, Sarah H Wild, Gonneke Willemsen, James F Wilson, Alan F Wright, Jie Yao, Tatijana Zemunik, Weihua Zhang, John R Attia, Adam S Butterworth, Daniel I Chasman, David Conen, Francesco Cucca, John Danesh, Caroline Hayward, Joanna Mm Howson, Markku Laakso, Edward G Lakatta, Claudia Langenberg, Olle Melander, Dennis O Mook-Kanamori, Colin Na Palmer, Lorenz Risch, Robert A Scott, Rodney J Scott, Peter Sever, Tim D Spector, Pim van der Harst, Nicholas J Wareham, Eleftheria Zeggini, Daniel Levy, Patricia B Munroe, Christopher Newton-Cheh, Morris J Brown, Andres Metspalu, Bruce M Psaty, Louise V Wain, Paul Elliott, Mark J Caulfield, Padhraig Gormley, Verneri Anttila, Priit Palta, Tonu Esko, Tune H Pers, Kai-How Farh, Ester Cuenca-Leon, Mikko Muona, Nicholas A Furlotte, Tobias Kurth, Andres Ingason, George McMahon, Lannie Ligthart, Gisela M Terwindt, Mikko Kallela, Tobias M Freilinger, Caroline Ran, Scott G Gordon, Anine H Stam, Stacy Steinberg, Guntram Borck, Markku Koiranen, Lydia Quaye, Hieab H H Adams, Terho Lehtimäki, Antti-Pekka Sarin, Juho Wedenoja, David A Hinds, Julie E Buring, Markus Schürks, Paul M Ridker, Maria Gudlaug Hrafnsdottir, Hreinn Stefansson, Susan M Ring, Jouke-Jan Hottenga, Brenda W J H Penninx, Markus Färkkilä, Ville Artto, Mari Kaunisto, Salli Vepsäläinen, Rainer Malik, Andrew C Heath, Pamela A F Madden, Nicholas G Martin, Grant W Montgomery, Mitja I Kurki, Mart Kals, Reedik Mägi, Kalle Pärn, Eija Hämäläinen, Hailiang Huang, Andrea E Byrnes, Lude Franke, Jie Huang, Evie Stergiakouli, Phil H Lee, Cynthia Sandor, Caleb Webber, Zameel Cader, Bertram Muller-Myhsok, Stefan Schreiber, Thomas Meitinger, Johan G Eriksson, Veikko Salomaa, Kauko Heikkilä, Elizabeth Loehrer, Andre G Uitterlinden, Albert Hofman, Cornelia M van Duijn, Lynn Cherkas, Linda M Pedersen, Audun Stubhaug, Christopher S Nielsen, Minna Männikkö, Evelin Mihailov, Lili Milani, Hartmut Göbel, Ann-Louise Esserlind, Anne Francke Christensen, Thomas Folkmann Hansen, Thomas Werge, Jaakko Kaprio, Arpo J Aromaa, Olli Raitakari, M Arfan Ikram, Tim Spector, Marjo-Riitta Järvelin, Andres Metspalu, Christian Kubisch, David P Strachan, Michel D Ferrari, Andrea C Belin, Martin Dichgans, Maija Wessman, Arn M J M van den Maagdenberg, Dorret I Boomsma, George Davey Smith, Kari Stefansson, Nicholas Eriksson, Mark J Daly, Benjamin M Neale, Jes Olesen, Daniel I Chasman, Dale R Nyholt, Aarno Palotie, Masato Akiyama, Varinder S Alg, Sigrid Børte, Joseph P Broderick, Ben M Brumpton, Jérôme Dauvillier, Hubert Desal, Christian Dina, Christoph M Friedrich, Emília I Gaál-Paavola, Jean-Christophe Gentric, Sven Hirsch, Isabel C Hostettler, Henry Houlden, Kristian Hveem, Juha E Jääskeläinen, Marianne Bakke Johnsen, Liming Li, Kuang Lin, Antti Lindgren, Olivier Martin, Koichi Matsuda, Iona Y Millwood, Olivier Naggara, Mika Niemelä, Joanna Pera, Richard Redon, Guy A Rouleau, Marie Søfteland Sandvei, Sabine Schilling, Eimad Shotar, Agnieszka Slowik, Chikashi Terao, W M Monique Verschuren, Robin G Walters, David J Werring, Cristen J Willer, Daniel Woo, Bradford B Worrall, Sirui Zhou, Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, and Admin, Oskar
Subjects: Advanced and Specialized Nursing, Incidence, risk assessment, Smoking/epidemiology, intracranial aneurysm, genetic heterogeneity, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Risk Factors, Intracranial Aneurysm/epidemiology, Humans, Subarachnoid Hemorrhage/epidemiology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, genetics, Neurology (clinical), aneurysmal subarachnoid hemorrhage, genetic, Cardiology and Cardiovascular Medicine
Abstract: 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 −3 per year [95% CI, −6.49×10 −3 to −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.
Published: 2023

14. Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Author: Niamh Mullins, JooEun Kang, Adrian I. Campos, Jonathan R.I. Coleman, Alexis C. Edwards, Hanga Galfalvy, Daniel F. Levey, Adriana Lori, Andrey Shabalin, Anna Starnawska, Mei-Hsin Su, Hunna J. Watson, Mark Adams, Swapnil Awasthi, Michael Gandal, Jonathan D. Hafferty, Akitoyo Hishimoto, Minsoo Kim, Satoshi Okazaki, Ikuo Otsuka, Stephan Ripke, Erin B. Ware, Andrew W. Bergen, Wade H. Berrettini, Martin Bohus, Harry Brandt, Xiao Chang, Wei J. Chen, Hsi-Chung Chen, Steven Crawford, Scott Crow, Emily DiBlasi, Philibert Duriez, Fernando Fernández-Aranda, Manfred M. Fichter, Steven Gallinger, Stephen J. Glatt, Philip Gorwood, Yiran Guo, Hakon Hakonarson, Katherine A. Halmi, Hai-Gwo Hwu, Sonia Jain, Stéphane Jamain, Susana Jiménez-Murcia, Craig Johnson, Allan S. Kaplan, Walter H. Kaye, Pamela K. Keel, James L. Kennedy, Kelly L. Klump, Dong Li, Shih-Cheng Liao, Klaus Lieb, Lisa Lilenfeld, Chih-Min Liu, Pierre J. Magistretti, Christian R. Marshall, James E. Mitchell, Eric T. Monson, Richard M. Myers, Dalila Pinto, Abigail Powers, Nicolas Ramoz, Stefan Roepke, Vsevolod Rozanov, Stephen W. Scherer, Christian Schmahl, Marcus Sokolowski, Michael Strober, Laura M. Thornton, Janet Treasure, Ming T. Tsuang, Stephanie H. Witt, D. Blake Woodside, Zeynep Yilmaz, Lea Zillich, Rolf Adolfsson, Ingrid Agartz, Tracy M. Air, Martin Alda, Lars Alfredsson, Ole A. Andreassen, Adebayo Anjorin, Vivek Appadurai, María Soler Artigas, Sandra Van der Auwera, M. Helena Azevedo, Nicholas Bass, Claiton H.D. Bau, Bernhard T. Baune, Frank Bellivier, Klaus Berger, Joanna M. Biernacka, Tim B. Bigdeli, Elisabeth B. Binder, Michael Boehnke, Marco P. Boks, Rosa Bosch, David L. Braff, Richard Bryant, Monika Budde, Enda M. Byrne, Wiepke Cahn, Miguel Casas, Enrique Castelao, Jorge A. Cervilla, Boris Chaumette, Sven Cichon, Aiden Corvin, Nicholas Craddock, David Craig, Franziska Degenhardt, Srdjan Djurovic, Howard J. Edenberg, Ayman H. Fanous, Jerome C. Foo, Andreas J. Forstner, Mark Frye, Janice M. Fullerton, Justine M. Gatt, Pablo V. Gejman, Ina Giegling, Hans J. Grabe, Melissa J. Green, Eugenio H. Grevet, Maria Grigoroiu-Serbanescu, Blanca Gutierrez, Jose Guzman-Parra, Steven P. Hamilton, Marian L. Hamshere, Annette Hartmann, Joanna Hauser, Stefanie Heilmann-Heimbach, Per Hoffmann, Marcus Ising, Ian Jones, Lisa A. Jones, Lina Jonsson, René S. Kahn, John R. Kelsoe, Kenneth S. Kendler, Stefan Kloiber, Karestan C. Koenen, Manolis Kogevinas, Bettina Konte, Marie-Odile Krebs, Mikael Landén, Jacob Lawrence, Marion Leboyer, Phil H. Lee, Douglas F. Levinson, Calwing Liao, Jolanta Lissowska, Susanne Lucae, Fermin Mayoral, Susan L. McElroy, Patrick McGrath, Peter McGuffin, Andrew McQuillin, Sarah E. Medland, Divya Mehta, Ingrid Melle, Yuri Milaneschi, Philip B. Mitchell, Esther Molina, Gunnar Morken, Preben Bo Mortensen, Bertram Müller-Myhsok, Caroline Nievergelt, Vishwajit Nimgaonkar, Markus M. Nöthen, Michael C. O’Donovan, Roel A. Ophoff, Michael J. Owen, Carlos Pato, Michele T. Pato, Brenda W.J.H. Penninx, Jonathan Pimm, Giorgio Pistis, James B. Potash, Robert A. Power, Martin Preisig, Digby Quested, Josep Antoni Ramos-Quiroga, Andreas Reif, Marta Ribasés, Vanesa Richarte, Marcella Rietschel, Margarita Rivera, Andrea Roberts, Gloria Roberts, Guy A. Rouleau, Diego L. Rovaris, Dan Rujescu, Cristina Sánchez-Mora, Alan R. Sanders, Peter R. Schofield, Thomas G. Schulze, Laura J. Scott, Alessandro Serretti, Jianxin Shi, Stanley I. Shyn, Lea Sirignano, Pamela Sklar, Olav B. Smeland, Jordan W. Smoller, Edmund J.S. Sonuga-Barke, Gianfranco Spalletta, John S. Strauss, Beata Świątkowska, Maciej Trzaskowski, Gustavo Turecki, Laura Vilar-Ribó, John B. Vincent, Henry Völzke, James T.R. Walters, Cynthia Shannon Weickert, Thomas W. Weickert, Myrna M. Weissman, Leanne M. Williams, Naomi R. Wray, Clement C. Zai, Allison E. Ashley-Koch, Jean C. Beckham, Elizabeth R. Hauser, Michael A. Hauser, Nathan A. Kimbrel, Jennifer H. 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Derks, Nese Direk, Conor V. Dolan, Erin C. Dunn, Thalia C. Eley, Valentina Escott-Price, Farnush Farhadi Hassan Kiadeh, Hilary K. Finucane, Josef Frank, Héléna A. Gaspar, Michael Gill, Fernando S. Goes, Scott D. Gordon, Shantel Marie Weinsheimer, Jürgen Wellmann, Gonneke Willemsen, Yang Wu, Hualin S. Xi, Jian Yang, Futao Zhang, Volker Arolt, Dorret I. Boomsma, Udo Dannlowski, E.J.C. de Geus, J. Raymond Depaulo, Enrico Domenici, Katharina Domschke, Jakob Grove, Lynsey S. Hall, Christine Søholm Hansen, Thomas F. Hansen, Stefan Herms, Ian B. Hickie, Georg Homuth, Carsten Horn, Jouke-Jan Hottenga, David M. Howard, Rick Jansen, Eric Jorgenson, James A. Knowles, Isaac S. Kohane, Julia Kraft, Warren W. Kretzschmar, Zoltán Kutalik, Yihan Li, Penelope A. Lind, Donald J. MacIntyre, Dean F. MacKinnon, Robert M. Maier, Wolfgang Maier, Jonathan Marchini, Hamdi Mbarek, Christel M. Middeldorp, Evelin Mihailov, Lili Milani, Francis M. Mondimore, Grant W. 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Regeer, Fabio Rivas, Julian Roth, Panos Roussos, Fanny Senner, Sally Sharp, Paul D. Shilling, Claire Slaney, Janet L. Sobell, Maria Soler Artigas, Anne T. Spijker, Dan J. Stein, Chikashi Terao, Claudio Toma, Paul Tooney, Evangelia-Eirini Tsermpini, Marquis P. Vawter, Helmut Vedder, Simon Xi, Wei Xu, Jessica Mei Kay Yang, Allan H. Young, Hannah Young, Peter P. Zandi, Hang Zhou, null HUNT All-In Psychiatry, Gulja Babadjanova, Lena Backlund, Susanne Bengesser, Douglas H.R. Blackwood, Vaughan J. Carr, Stanley Catts, Dimitris Dikeos, Bruno Etain, Panagiotis Ferentinos, Micha Gawlik, Elliot S. Gershon, Frans Henskens, Jan Hillert, Kyung Sue Hong, Christina M. Hultman, Kristian Hveem, Nakao Iwata, Assen V. Jablensky, George Kirov, Christine Lochner, Carmel Loughland, Carol A. Mathews, Francis J. McMahon, Patricia Michie, Bryan Mowry, Benjamin M. Neale, Caroline M. Nievergelt, Ketil J. Oedegaard, Tomas Olsson, Chris Pantelis, George P. Patrinos, Eva Z. 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J., Wasserman, D., Coon, H., Demontis, D., Docherty, A. R., Kuo, P. -H., Mann, J. J., Renteria, M. E., Stein, M. B., Willour, V., Psychiatry, Biological Psychology, APH - Methodology, APH - Mental Health, APH - Health Behaviors & Chronic Diseases, AMS - Sports, AMS - Ageing & Vitality, APH - Personalized Medicine, Amsterdam Neuroscience - Complex Trait Genetics, Complex Trait Genetics, Institute for Molecular Medicine Finland, Centre of Excellence in Complex Disease Genetics, Aarno Palotie / Principal Investigator, Genomics of Neurological and Neuropsychiatric Disorders, HUS Psychiatry, Department of Public Health, Clinicum, Nuorisopsykiatria, Faculty Common Matters (Faculty of Social Sciences), Samuli Olli Ripatti / Principal Investigator, Complex Disease Genetics, Biostatistics Helsinki, Anna Keski-Rahkonen / Principal Investigator, Elisabeth Ingrid Maria Widen / Principal Investigator, Genomic Discoveries and Clinical Translation, Internal medicine, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Digital Health, Mullins N., Kang J., Campos A.I., Coleman J.R.I., Edwards 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Subjects: LD SCORE REGRESSION, Genome-wide association study, Suicide, Attempted, 3124 Neurology and psychiatry, 0302 clinical medicine, Risk Factors, Insomnia, Suicide attempt, GWAS, Suïcidi, Depression (differential diagnoses), Cause of death, Psychiatry, 0303 health sciences, Factors de risc en les malalties, Mental Disorders, Genetic Correlation, Genome-wide Association Study, Pleiotropy, Polygenicity, Suicide, Suicide Attempt, DEPRESSION, 3. Good health, Genetic correlation, Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide, Depressive Disorder, Major, Mental illness, Cohort, SEX, medicine.symptom, Human, medicine.medical_specialty, Risk factors in diseases, BF, Locus (genetics), BEHAVIORS, Psykiatri, EVENTS, 03 medical and health sciences, SDG 3 - Good Health and Well-being, medicine, ddc:610, GENOME-WIDE ASSOCIATION, IDEATION, Socioeconomic status, METAANALYSIS, Biological Psychiatry, 030304 developmental biology, business.industry, Risk Factor, Genetic architecture, THOUGHTS, RC0321, business, Malalties mentals, 030217 neurology & neurosurgery
Abstract: Statistical analyses were carried out on the NL Genetic Cluster Computer (http://www.geneticcluster.org) hosted by SURFsara and the Mount Sinai high performance computing cluster (http://hpc.mssm.edu), which is supported by the Office of Research Infrastructure of the National Institutes of Health (Grant Nos. S10OD018522 and S10OD026880). This work was conducted in part using the resources of the Advanced Computing Center for Research and Education at Vanderbilt University, Nashville, TN. This work was funded by the National Institutes of Health (Grant Nos. R01MH116269 and R01MH121455 [to DMR]), NIGMS of the National Institutes of Health (Grant No. T32GM007347 [to JK]), and the Brain & Behavior Research Foundation (NARSAD Young Investigator Award No. 29551 [to NM])., BACKGROUND: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. METHODS: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. RESULTS: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. CONCLUSIONS: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders., Office of Research Infrastructure of the National Institutes of Health S10OD018522 S10OD026880, United States Department of Health & Human Services, National Institutes of Health (NIH) - USA R01MH116269 R01MH121455, NIH National Institute of General Medical Sciences (NIGMS) T32GM007347 NARSAD 29551
Published: 2022

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14 results on '"Winsvold, Bendik S"'

1. Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology

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

14. Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

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