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1. Fock space of local fields of the discrete GFF and its scaling limit bosonic CFT

Author

Adame-Carrillo, David, Behzad, Delara, and Kytölä, Kalle

Subjects
Mathematical Physics, Mathematics - Probability, 17B68, 30G25, 60G60, 60G15, 82B20, 82B23
Abstract

To connect conformal field theories (CFT) to probabilistic lattice models, recent works [HKV22, Ada23] have introduced a novel definition of local fields of the lattice models. Local fields in this picture are probabilistically concrete: they are built from random variables in the model. The key insight is that discrete complex analysis ideas allow to equip the space of local fields with the main structure of a CFT: a representation of the Virasoro algebra. In this article, for the first time, we fully analyze the structure of the space of local fields of a lattice model as a representation, and use this to establish a one-to-one correspondence between the local fields of a lattice model and those of a conformal field theory. The CFT we consider is probabilistically realized in terms of the gradient of the Gaussian Free Field (GFF). Its space of local fields is just a bosonic Fock space for two chiral symmetry algebras. The corresponding lattice model is the discrete Gaussian Free Field. Our first main result is that the space of local fields of polynomials in the gradient of the discrete GFF is isomorphic to the Fock space. These local fields make sense with both Dirichlet and Neumann boundary conditions. Our second main result is that with the appropriate renormalization, correlation functions of local fields of the discrete GFF converge in the scaling limit to the correlation functions of the CFT. The renormalization needed is, conceptually correctly, according to the eigenvalue of the Virasoro generator $L_0 + \bar{L}_0$ on the local field., Comment: 84 pages, 14 figures, comments welcome! (v2: minor edits and misprint corrections)

Published
2024

3. Whole-genome sequencing identifies variants in ANK1, LRRN1, HAS1, and other genes and regulatory regions for stroke in type 1 diabetes

Author

Anni A. Antikainen, Jani K. Haukka, Anmol Kumar, Anna Syreeni, Stefanie Hägg-Holmberg, Anni Ylinen, Elina Kilpeläinen, Anastasia Kytölä, Aarno Palotie, Jukka Putaala, Lena M. Thorn, Valma Harjutsalo, Per-Henrik Groop, Niina Sandholm, and the FinnDiane Study Group

Subjects
Medicine, Science
Abstract

Abstract Individuals with type 1 diabetes (T1D) carry a markedly increased risk of stroke, with distinct clinical and neuroimaging characteristics as compared to those without diabetes. Using whole-exome or whole-genome sequencing of 1,051 individuals with T1D, we aimed to find rare and low-frequency genomic variants associated with stroke in T1D. We analysed the genome comprehensively with single-variant analyses, gene aggregate analyses, and aggregate analyses on genomic windows, enhancers and promoters. In addition, we attempted replication in T1D using a genome-wide association study (N = 3,945) and direct genotyping (N = 3,263), and in the general population from the large-scale population-wide FinnGen project and UK Biobank summary statistics. We identified a rare missense variant on SREBF1 exome-wide significantly associated with stroke (rs114001633, p.Pro227Leu, p-value = 7.30 × 10–8), which replicated for hemorrhagic stroke in T1D. Using gene aggregate analysis, we identified exome-wide significant genes: ANK1 and LRRN1 displayed replication evidence in T1D, and LRRN1, HAS1 and UACA in the general population (UK Biobank). Furthermore, we performed sliding-window analyses and identified 14 genome-wide significant windows for stroke on 4q33-34.1, of which two replicated in T1D, and a suggestive genomic window on LINC01500, which replicated in T1D. Finally, we identified a suggestively stroke-associated TRPM2-AS promoter (p-value = 5.78 × 10–6) with borderline significant replication in T1D, which we validated with an in vitro cell-based assay. Due to the rarity of the identified genetic variants, future replication of the genomic regions represented here is required with sequencing of individuals with T1D. Nevertheless, we here report the first genome-wide analysis on stroke in individuals with diabetes.

Published
2024
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5. TWINGEN: protocol for an observational clinical biobank recall and biomarker cohort study to identify Finnish individuals with high risk of Alzheimer’s disease

Author

Tommi Vasankari, Henri Vähä-Ypyä, Oskari Heikinheimo, Athena Matakidou, Jaakko Kaprio, Eero Vuoksimaa, Ying Wu, Kai Kaarniranta, Peeter Karihtala, Wei Zhou, Caroline Fox, Sanna-Kaisa Herukka, Sarah Smith, Apinya Lertratanakul, Katri Kaukinen, Johannes Kettunen, Minna Männikkö, Eeva Sliz, Markus Perola, Veikko Salomaa, Hilkka Soininen, Ilkka Kalliala, Mika Kähönen, Hao Chen, Andrey Loboda, Laure Morin-Papunen, Terhi Piltonen, Anders Mälarstig, Jason Miller, Jussi Hernesniemi, Henrike Heyne, Sirkku Peltonen, Daniel Gordin, Masahiro Kanai, Benjamin Challis, Juha Sinisalo, David Rice, Fredrik Åberg, Aarno Palotie, Samuli Ripatti, Oili Kaipiainen-Seppänen, Aki Havulinna, Satu Strausz, Tuomo Kiiskinen, Sanni Ruotsalainen, Jukka Koskela, Tuula Palotie, Mark Daly, Howard Jacob, Heiko Runz, Sally John, Robert Plenge, Mark McCarthy, Julie Hunkapiller, Dawn Waterworth, Petri Virolainen, Terhi Kilpi, Jukka Partanen, Anne Pitkäranta, Veli-Matti Kosma, Outi Tuovila, Raimo Pakkanen, Shameek Biswas, Xinli Hu, Johanna Schleutker, Mikko Arvas, Olli Carpen, Reetta Hinttala, Arto Mannermaa, Valtteri Julkunen, Anne Remes, Reetta Kälviäinen, Mikko Hiltunen, Jukka Peltola, Pentti Tienari, Juha Rinne, Adam Ziemann, Jeffrey Waring, Nizar Smaoui, Anne Lehtonen, Susan Eaton, Sanni Lahdenperä, Natalie Bowers, Edmond Teng, Fanli Xu, David Pulford, Martti Färkkilä, Sampsa Pikkarainen, Airi Jussila, Timo Blomster, Mikko Kiviniemi, Markku Voutilainen, Fedik Rahimov, Joseph Maranville, Tim Lu, Kirsi Kalpala, Melissa Miller, Linda McCarthy, Kari Eklund, Antti Palomäki, Pia Isomäki, Laura Pirilä, Johanna Huhtakangas, Marla Hochfeld, Nan Bing, Jorge Esparza Gordillo, Nina Mars, Tarja Laitinen, Margit Pelkonen, Paula Kauppi, Hannu Kankaanranta, Terttu Harju, Hubert Chen, Teemu Niiranen, Kaj Metsärinne, Marja-Riitta Taskinen, Tiinamaija Tuomi, Jari Laukkanen, Audrey Chu, Jaakko Parkkinen, Heikki Joensuu, Tuomo Meretoja, Lauri Aaltonen, Annika Auranen, Päivi Auvinen, Klaus Elenius, Relja Popovic, Bridget Riley-Gillis, Jennifer Schutzman, Heli Lehtonen, Stefan McDonough, Diptee Kulkarni, Terhi Ollila, Hannu Uusitalo, Erich Strauss, Kaisa Tasanen, Laura Huilaja, Katariina Hannula-Jouppi, Teea Salmi, Leena Koulu, David Choy, Anu Jalanko, Risto Kajanne, Mari Kaunisto, Chia-Yen Chen, Robert Yang, Kirsi Auro, Clement Chatelain, Mitja Kurki, Juha Karjalainen, Kimmo Palin, Priit Palta, Susanna Lemmelä, Manuel Rivas, Arto Lehisto, Andrea Ganna, Vincent Llorens, Kati Kristiansson, Kati Hyvärinen, Jarmo Ritari, Katri Pylkäs, Minna Karjalainen, Tuomo Mantere, Eeva Kangasniemi, Sami Heikkinen, Eija Laakkonen, Anu Loukola, Päivi Laiho, Tuuli Sistonen, Essi Kaiharju, Markku Laukkanen, Elina Järvensivu, Sini Lähteenmäki, Lotta Männikkö, Regis Wong, Hannele Mattsson, Tero Hiekkalinna, Kati Donner, Kalle Pärn, Elina Kilpeläinen, Hannele Laivuori, Harri Siirtola, Sirpa Soini, Teijo Kuopio, Ioanna Tachmazidou, Katja Kivinen, Pekka Nieminen, Adam Platt, Sanna Toppila-Salmi, Antti Mäkitie, Elmo Saarentaus, Kristiina Aittomäki, Elisabeth Widen, Marja Vääräsmäki, Erkki Isometsä, Laura Addis, Mika Helminen, Taneli Raivio, Mart Kals, Majd Mouded, Hanna Ollila, Vuokko Anttonen, Tarja Kokkola, Robert Graham, Amanda Elliott, Ali Abbasi, Bridget Riley-Gills, Dirk Paul, Katherine Klinger, Deepak Raipal, Antti Hakanen, Raisa Serpi, Johanna Mäkelä, Mengzhen Liu, Neha Raghavan, Adriana Huertas-Vazquez, Nicole Renaud, Roosa Kallionpää, John Eicher, Minna Raivio, Juulia Partanen, Riitta Lahesmaa, Glenda Lassi, Joanna Betts, Rajashree Mishra, Felix Vaura, Joel Rämö, Mary Pat Reeve, Johanna Mattson, Sauli Vuoti, Esa Pitkänen, Joni A Turunen, Stephanie Loomis, Pirkko Pussinen, Aino Salminen, Tuula Salo, Ulla Palotie, Maria Siponen, Liisa Suominen, Päivi Mäntylä, Ulvi Gursoy, Kirsi Sipilä, Venla Kurra, Laura Kotaniemi-Talonen, Outi Uimari, Taru Tukiainen, Niko Välimäki, Janet Kumar, Juha Mehtonen, Shabbeer Hassan, Pietro Della Briotta Parolo, Mutaamba Maasha, Javier Garcia-Tabuenca, Jiwoo Lee, Kristin Tsuo, Nina Pitkänen, Eero Punkka, Huei-Yi Shen, Mervi Aavikko, L. Elisa Lahtela, Timo P. Sipilä, Awaisa Ghazal, Sami Koskelainen, Teemu Paajanen, Shuang Luo, Javier Gracia-Tabuenca, Tiina Luukkaala, Iida Vähätalo, Marco Hautalahti, Tom Southerington, Paula Iso-Markku, Jaana Suvisaari, Zhihao Ding, Qingqin S Li, Amy Hart, Perttu Terho, Alessandro Porello, Anastasia Kytölä, Antti Aarnisalo, Aoxing Liu, Argyro Bizaki-Vallaskangas, Auli Toivola, Debby Ngo, Dermot Reilly, Ekaterina Khramtsova, Elisa Rahikkala, Eric Green, Eveliina Salminen, Fabiana Farias, George Okafo, Heidi Silven, Heli Salminen-Mankonen, Henna Palin, Iiris Hovatta, Jaakko Tyrmi, Jae-Hoon Sul, Jenni Aittokallio, Jyrki Pitkänen, Karen He, Katriina Aalto-Setälä, Maarit Niinimäki, Malla-Maria Linna, Marc Jung, Margaret G. Ehm, Marianna Niemi, Meijian Guan, Mike Mendelson, Minna Brunfeldt, Natalia Pujol, Nathan Lawless, Oluwaseun Alexander Dada, Rigbe Weldatsadik, Riikka Arffman, Rion Pendergrass, Sahar Mozaffari, Samuel Lessard, Sanna Siltanen, Shanmukha Sampath Padmanabhuni, Simonne Longerich, Susanna Savukoski, Thomas Damm Als, Timo Hiltunen, Tomi P. Mäkelä, Triin Laisk, Tytti Willberg, Varpu Jokimaa, Aija Kyttälä, Toni T Saari, Aino Aaltonen, Sari Aaltonen, Sari Kärkkäinen, Hilkka Liedes, Miina Ollikainen, Teemu Palviainen, Ilona Ruotsalainen, Mia Urjansson, Markus M Forsberg, Jaakko Lähteenmäki, Pia Nyberg, Jani Tikkanen, Mari E. Niemi, and Rodos Rodosthenous

Subjects
Medicine
Abstract

Introduction A better understanding of the earliest stages of Alzheimer’s disease (AD) could expedite the development or administration of treatments. Large population biobanks hold the promise to identify individuals at an elevated risk of AD and related dementias based on health registry information. Here, we establish the protocol for an observational clinical recall and biomarker study called TWINGEN with the aim to identify individuals at high risk of AD by assessing cognition, health and AD-related biomarkers. Suitable candidates were identified and invited to participate in the new study among THL Biobank donors according to TWINGEN study criteria.Methods and analysis A multi-centre study (n=800) to obtain blood-based biomarkers, telephone-administered and web-based memory and cognitive parameters, questionnaire information on lifestyle, health and psychological factors, and accelerometer data for measures of physical activity, sedentary behaviour and sleep. A subcohort is being asked to participate in an in-person neuropsychological assessment (n=200) and wear an Oura ring (n=50). All participants in the TWINGEN study have genome-wide genotyping data and up to 48 years of follow-up data from the population-based older Finnish Twin Cohort (FTC) study of the University of Helsinki. The data collected in TWINGEN will be returned to THL Biobank from where it can later be requested for other biobank studies such as FinnGen that supported TWINGEN.Ethics and dissemination This recall study consists of FTC/THL Biobank/FinnGen participants whose data were acquired in accordance with the Finnish Biobank Act. The recruitment protocols followed the biobank protocols approved by Finnish Medicines Agency. The TWINGEN study plan was approved by the Ethics Committee of Hospital District of Helsinki and Uusimaa (number 16831/2022). THL Biobank approved the research plan with the permission no: THLBB2022_83.

Published
2024
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6. Thrombosis risk in single- and double-heterozygous carriers of factor V Leiden and prothrombin G20210A in FinnGen and the UK Biobank

Author

Palotie, Aarno, Daly, Mark, Riley-Gills, Bridget, Jacob, Howard, Viollet, Coralie, Petrovski, Slavé, Chen, Chia-Yen, John, Sally, Okafo, George, Plenge, Robert, Maranville, Joseph, McCarthy, Mark, Pendergrass, Rion, Ehm, Margaret G., Auro, Kirsi, Longerich, Simonne, Mälarstig, Anders, Vlahiotis, Anna, Klinger, Katherine, Chatelain, Clement, Gossel, Matthias, Estrada, Karol, Graham, Robert, Waterworth, Dawn, O´Donnell, Chris, Renaud, Nicole, Mäkelä, Tomi P., Kaprio, Jaakko, Ruddock, Minna, Virolainen, Petri, Hakanen, Antti, Kilpi, Terhi, Perola, Markus, Partanen, Jukka, Raivio, Taneli, Tikkanen, Jani, Serpi, Raisa, Kristiansson, Kati, Kosma, Veli-Matti, Laukkanen, Jari, Hautalahti, Marco, Tuovila, Outi, Waring, Jeffrey, Riley-Gillis, Bridget, Rahimov, Fedik, Tachmazidou, Ioanna, Ding, Zhihao, Jung, Marc, Tuoken, Hanati, Biswas, Shameek, Pulford, David, Raghavan, Neha, Huertas-Vazquez, Adriana, Sul, Jae-Hoon, Hu, Xinli, Hedman, Åsa, Obeidat, Ma´en, Chung, Jonathan, Zierer, Jonas, Niemi, Mari, Ripatti, Samuli, Schleutker, Johanna, Arvas, Mikko, Carpén, Olli, Hinttala, Reetta, Kettunen, Johannes, Mannermaa, Arto, Aalto-Setälä, Katriina, Kähönen, Mika, Mäkelä, Johanna, Kälviäinen, Reetta, Julkunen, Valtteri, Soininen, Hilkka, Remes, Anne, Hiltunen, Mikko, Peltola, Jukka, Raivio, Minna, Tienari, Pentti, Rinne, Juha, Kallionpää, Roosa, Partanen, Juulia, Ziemann, Adam, Smaoui, Nizar, Lehtonen, Anne, Eaton, Susan, Runz, Heiko, Lahdenperä, Sanni, Bowers, Natalie, Teng, Edmond, Xu, Fanli, Addis, Laura, Eicher, John, Li, Qingqin S., He, Karen, Khramtsova, Ekaterina, Färkkilä, Martti, Koskela, Jukka, Pikkarainen, Sampsa, Jussila, Airi, Kaukinen, Katri, Blomster, Timo, Kiviniemi, Mikko, Voutilainen, Markku, Lu, Tim, McCarthy, Linda, Hart, Amy, Guan, Meijian, Miller, Jason, Kalpala, Kirsi, Miller, Melissa, Eklund, Kari, Palomäki, Antti, Isomäki, Pia, Pirilä, Laura, Kaipiainen-Seppänen, Oili, Huhtakangas, Johanna, Mars, Nina, Lertratanakul, Apinya, Hochfeld, Marla, Gordillo, Jorge Esparza, Farias, Fabiana, Bing, Nan, Laitinen, Tarja, Pelkonen, Margit, Kauppi, Paula, Kankaanranta, Hannu, Harju, Terttu, Lahesmaa, Riitta, Chen, Hubert, Betts, Joanna, Mishra, Rajashree, Mouded, Majd, Ngo, Debby, Niiranen, Teemu, Vaura, Felix, Salomaa, Veikko, Metsärinne, Kaj, Aittokallio, Jenni, Hernesniemi, Jussi, Gordin, Daniel, Sinisalo, Juha, Taskinen, Marja-Riitta, Tuomi, Tiinamaija, Hiltunen, Timo, Elliott, Amanda, Reeve, Mary Pat, Ruotsalainen, Sanni, Paul, Dirk, Chu, Audrey, Reilly, Dermot, Mendelson, Mike, Parkkinen, Jaakko, Meretoja, Tuomo, Joensuu, Heikki, Mattson, Johanna, Salminen, Eveliina, Auranen, Annika, Karihtala, Peeter, Auvinen, Päivi, Elenius, Klaus, Pitkänen, Esa, Popovic, Relja, Fabre, Margarete, Schutzman, Jennifer, Kulkarni, Diptee, Porello, Alessandro, Loboda, Andrey, Lehtonen, Heli, McDonough, Stefan, Vuoti, Sauli, Kaarniranta, Kai, Turunen, Joni A., Ollila, Terhi, Uusitalo, Hannu, Karjalainen, Juha, Liu, Mengzhen, Loomis, Stephanie, Strauss, Erich, Chen, Hao, Tasanen, Kaisa, Huilaja, Laura, Hannula-Jouppi, Katariina, Salmi, Teea, Peltonen, Sirkku, Koulu, Leena, Choy, David, Wu, Ying, Pussinen, Pirkko, Salminen, Aino, Salo, Tuula, Rice, David, Nieminen, Pekka, Palotie, Ulla, Siponen, Maria, Suominen, Liisa, Mäntylä, Päivi, Gursoy, Ulvi, Anttonen, Vuokko, Sipilä, Kirsi, Laivuori, Hannele, Kurra, Venla, Kotaniemi-Talonen, Laura, Heikinheimo, Oskari, Kalliala, Ilkka, Aaltonen, Lauri, Jokimaa, Varpu, Vääräsmäki, Marja, Uimari, Outi, Morin-Papunen, Laure, Niinimäki, Maarit, Piltonen, Terhi, Kivinen, Katja, Widen, Elisabeth, Tukiainen, Taru, Välimäki, Niko, Laakkonen, Eija, Tyrmi, Jaakko, Silven, Heidi, Sliz, Eeva, Arffman, Riikka, Savukoski, Susanna, Laisk, Triin, Pujol, Natalia, Kumar, Janet, Hovatta, Iiris, Isometsä, Erkki, Ollila, Hanna, Suvisaari, Jaana, Mäkitie, Antti, Bizaki-Vallaskangas, Argyro, Toppila-Salmi, Sanna, Willberg, Tytti, Saarentaus, Elmo, Aarnisalo, Antti, Rahikkala, Elisa, Aittomäki, Kristiina, Åberg, Fredrik, Kurki, Mitja, Havulinna, Aki, Mehtonen, Juha, Palta, Priit, Hassan, Shabbeer, Della Briotta Parolo, Pietro, Zhou, Wei, Maasha, Mutaamba, Lemmelä, Susanna, Rivas, Manuel, Liu, Aoxing, Lehisto, Arto, Ganna, Andrea, Llorens, Vincent, Heyne, Henrike, Rämö, Joel, Rodosthenous, Rodos, Strausz, Satu, Palotie, Tuula, Palin, Kimmo, Garcia-Tabuenca, Javier, Siirtola, Harri, Kiiskinen, Tuomo, Lee, Jiwoo, Tsuo, Kristin, Hyvärinen, Kati, Ritari, Jarmo, Pylkäs, Katri, Karjalainen, Minna, Mantere, Tuomo, Kangasniemi, Eeva, Heikkinen, Sami, Pitkänen, Nina, Lessard, Samuel, Chatelain, Clément, Kallio, Lila, Wahlfors, Tiina, Punkka, Eero, Siltanen, Sanna, Kuopio, Teijo, Jalanko, Anu, Shen, Huei-Yi, Kajanne, Risto, Aavikko, Mervi, Cooper, Helen, Öller, Denise, Leinonen, Rasko, Palin, Henna, Linna, Malla-Maria, Kanai, Masahiro, Zheng, Zhili, Lahtela, L. Elisa, Kaunisto, Mari, Kilpeläinen, Elina, Sipilä, Timo P., Dada, Oluwaseun Alexander, Ghazal, Awaisa, Kytölä, Anastasia, Weldatsadik, Rigbe, Donner, Kati, Loukola, Anu, Laiho, Päivi, Sistonen, Tuuli, Kaiharju, Essi, Laukkanen, Markku, Järvensivu, Elina, Lähteenmäki, Sini, Männikkö, Lotta, Wong, Regis, Toivola, Auli, Brunfeldt, Minna, Mattsson, Hannele, Koskelainen, Sami, Hiekkalinna, Tero, Paajanen, Teemu, Luo, Shuang, Padmanabhuni, Shanmukha Sampath, Niemi, Marianna, Gracia-Tabuenca, Javier, Helminen, Mika, Luukkaala, Tiina, Vähätalo, Iida, Tammerluoto, Jyrki, Smith, Sarah, Southerington, Tom, Lehto, Petri, Ryu, Justine, Rämö, Joel T., Jurgens, Sean J., Sanna-Cherchi, Simone, Bauer, Kenneth A., Haj, Amelia, Choi, Seung Hoan, Ellinor, Patrick T., and Bendapudi, Pavan K.

Published
2024
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7. Slit-strip Ising boundary conformal field theory 2: Scaling limits of fusion coefficients

Author

Ameen, Taha, Kytölä, Kalle, and Park, S. C.

Subjects
Mathematical Physics, Mathematics - Probability
Abstract

This is the second in a series of three articles about recovering the full algebraic structure of a boundary conformal field theory (CFT) from the scaling limit of the critical Ising model in slit-strip geometry. Here we study the fusion coefficients of the Ising model in the lattice slit-strip, with locally monochromatic boundary conditions. The fusion coefficients are certain renormalized limits of boundary correlation functions at the three extremities of the truncated lattice slit-strips, in a basis of random variables whose correlation functions have an essentially exponential dependence on the truncation heights. The key technique is to associate operator valued discrete 1-forms to certain discrete holomorphic functions. This provides a direct analogy with currents in boundary conformal field theory. For two specific applications of this technique, we use distinguished discrete holomorphic functions from the first article of the series. First, we rederive the known diagonalization of the Ising transfer matrix in a form that parallels boundary conformal field theory. Second, we characterize the Ising model fusion coefficients by a recursion written purely in terms of inner products of the distinguished discrete holomorphic functions. The convergence result for the discrete holomorphic functions proven in the first part can then be used to derive the convergence of the fusion coefficients in the scaling limit. In the third article of the series, it will be shown that up to a transformation that accounts for our chosen slit-strip geometry, the scaling limits of the fusion coefficients become the structure constants of the vertex operator algebra of a fermionic conformal field theory., Comment: 82 pages, 25 figures

Published
2021

8. High-Resolution Genotyping of Formalin-Fixed Tissue Accurately Estimates Polygenic Risk Scores in Human Diseases

Author

Palotie, Aarno, Daly, Mark, Riley-Gills, Bridget, Jacob, Howard, Paul, Dirk, Petrovski, Slavé, Runz, Heiko, John, Sally, Okafo, George, Lawless, Nathan, Salminen-Mankonen, Heli, Plenge, Robert, Maranville, Joseph, McCarthy, Mark, Ehm, Margaret G., Auro, Kirsi, Longerich, Simonne, Mälarstig, Anders, Klinger, Katherine, Chatelain, Clement, Gossel, Matthias, Estrada, Karol, Graham, Robert, Yang, Robert, ODonnell, Chris, Mäkelä, Tomi P., Kaprio, Jaakko, Virolainen, Petri, Hakanen, Antti, Kilpi, Terhi, Perola, Markus, Partanen, Jukka, Pitkäranta, Anne, Raivio, Taneli, Tikkanen, Jani, Serpi, Raisa, Laitinen, Tarja, Kosma, Veli-Matti, Laukkanen, Jari, Hautalahti, Marco, Tuovila, Outi, Pakkanen, Raimo, Waring, Jeffrey, Riley-Gillis, Bridget, Rahimov, Fedik, Tachmazidou, Ioanna, Chen, Chia-Yen, Ding, Zhihao, Jung, Marc, Biswas, Shameek, Pendergrass, Rion, Pulford, David, Raghavan, Neha, Huertas-Vazquez, Adriana, Sul, Jae-Hoon, Hu, Xinli, Hedman, Åsa, Rivas, Manuel, Waterworth, Dawn, Renaud, Nicole, Obeidat, Maen, Ripatti, Samuli, Schleutker, Johanna, Arvas, Mikko, Carpén, Olli, Hinttala, Reetta, Kettunen, Johannes, Mannermaa, Arto, Aalto-Setälä, Katriina, Kähönen, Mika, Mäkelä, Johanna, Kälviäinen, Reetta, Julkunen, Valtteri, Soininen, Hilkka, Remes, Anne, Hiltunen, Mikko, Peltola, Jukka, Raivio, Minna, Tienari, Pentti, Rinne, Juha, Kallionpää, Roosa, Partanen, Juulia, Abbasi, Ali, Ziemann, Adam, Smaoui, Nizar, Lehtonen, Anne, Eaton, Susan, Lahdenperä, Sanni, Bowers, Natalie, Teng, Edmond, Xu, Fanli, Addis, Laura, Eicher, John, Li, Qingqin S., He, Karen, Khramtsova, Ekaterina, Färkkilä, Martti, Koskela, Jukka, Pikkarainen, Sampsa, Jussila, Airi, Kaukinen, Katri, Blomster, Timo, Kiviniemi, Mikko, Voutilainen, Markku, Lu, Tim, McCarthy, Linda, Hart, Amy, Guan, Meijian, Miller, Jason, Kalpala, Kirsi, Miller, Melissa, Eklund, Kari, Palomäki, Antti, Isomäki, Pia, Pirilä, Laura, Kaipiainen-Seppänen, Oili, Huhtakangas, Johanna, Mars, Nina, Lertratanakul, Apinya, Viollet, Coralie, Hochfeld, Marla, Gordillo, Jorge Esparza, Farias, Fabiana, Bing, Nan, Pelkonen, Margit, Kauppi, Paula, Kankaanranta, Hannu, Harju, Terttu, Lahesmaa, Riitta, Chen, Hubert, Betts, Joanna, Mishra, Rajashree, Mouded, Majd, Ngo, Debby, Niiranen, Teemu, Vaura, Felix, Salomaa, Veikko, Metsärinne, Kaj, Aittokallio, Jenni, Hernesniemi, Jussi, Gordin, Daniel, Sinisalo, Juha, Taskinen, Marja-Riitta, Tuomi, Tiinamaija, Hiltunen, Timo, Elliott, Amanda, Reeve, Mary Pat, Ruotsalainen, Sanni, Chu, Audrey, Reilly, Dermot, Mendelson, Mike, Parkkinen, Jaakko, Meretoja, Tuomo, Joensuu, Heikki, Mattson, Johanna, Salminen, Eveliina, Auranen, Annika, Karihtala, Peeter, Auvinen, Päivi, Elenius, Klaus, Pitkänen, Esa, Popovic, Relja, Fabre, Margarete, Schutzman, Jennifer, Kulkarni, Diptee, Porello, Alessandro, Loboda, Andrey, Lehtonen, Heli, McDonough, Stefan, Vuoti, Sauli, Kaarniranta, Kai, Turunen, Joni A., Ollila, Terhi, Uusitalo, Hannu, Karjalainen, Juha, Liu, Mengzhen, Loomis, Stephanie, Strauss, Erich, Chen, Hao, Tasanen, Kaisa, Huilaja, Laura, Hannula-Jouppi, Katariina, Salmi, Teea, Peltonen, Sirkku, Koulu, Leena, Choy, David, Wu, Ying, Pussinen, Pirkko, Salminen, Aino, Salo, Tuula, Rice, David, Nieminen, Pekka, Palotie, Ulla, Siponen, Maria, Suominen, Liisa, Mäntylä, Päivi, Gursoy, Ulvi, Anttonen, Vuokko, Sipilä, Kirsi, Laivuori, Hannele, Kurra, Venla, Kotaniemi-Talonen, Laura, Heikinheimo, Oskari, Kalliala, Ilkka, Aaltonen, Lauri, Jokimaa, Varpu, Vääräsmäki, Marja, Uimari, Outi, Morin-Papunen, Laure, Niinimäki, Maarit, Piltonen, Terhi, Kivinen, Katja, Widen, Elisabeth, Tukiainen, Taru, Välimäki, Niko, Laakkonen, Eija, Tyrmi, Jaakko, Silven, Heidi, Sliz, Eeva, Arffman, Riikka, Savukoski, Susanna, Laisk, Triin, Pujol, Natalia, Kumar, Janet, Hovatta, Iiris, Isometsä, Erkki, Ollila, Hanna, Suvisaari, Jaana, Als, Thomas Damm, Mäkitie, Antti, Bizaki-Vallaskangas, Argyro, Toppila-Salmi, Sanna, Willberg, Tytti, Saarentaus, Elmo, Aarnisalo, Antti, Rahikkala, Elisa, Aittomäki, Kristiina, Åberg, Fredrik, Kurki, Mitja, Havulinna, Aki, Mehtonen, Juha, Palta, Priit, Hassan, Shabbeer, Della Briotta Parolo, Pietro, Zhou, Wei, Maasha, Mutaamba, Lemmelä, Susanna, Liu, Aoxing, Lehisto, Arto, Ganna, Andrea, Llorens, Vincent, Heyne, Henrike, Rämö, Joel, Rodosthenous, Rodos, Strausz, Satu, Palotie, Tuula, Palin, Kimmo, Garcia-Tabuenca, Javier, Siirtola, Harri, Kiiskinen, Tuomo, Lee, Jiwoo, Tsuo, Kristin, Kristiansson, Kati, Hyvärinen, Kati, Ritari, Jarmo, Pylkäs, Katri, Karjalainen, Minna, Mantere, Tuomo, Kangasniemi, Eeva, Heikkinen, Sami, Pitkänen, Nina, Lessard, Samuel, Chatelain, Clément, Kallio, Lila, Wahlfors, Tiina, Punkka, Eero, Siltanen, Sanna, Kuopio, Teijo, Jalanko, Anu, Shen, Huei-Yi, Kajanne, Risto, Aavikko, Mervi, Cooper, Helen, Öller, Denise, Leinonen, Rasko, Palin, Henna, Linna, Malla-Maria, Kanai, Masahiro, Zheng, Zhili, Lahtela, L. Elisa, Kaunisto, Mari, Kilpeläinen, Elina, Sipilä, Timo P., Dada, Oluwaseun Alexander, Ghazal, Awaisa, Kytölä, Anastasia, Weldatsadik, Rigbe, Donner, Kati, Loukola, Anu, Laiho, Päivi, Sistonen, Tuuli, Kaiharju, Essi, Laukkanen, Markku, Järvensivu, Elina, Lähteenmäki, Sini, Männikkö, Lotta, Wong, Regis, Toivola, Auli, Brunfeldt, Minna, Mattsson, Hannele, Koskelainen, Sami, Hiekkalinna, Tero, Paajanen, Teemu, Pärn, Kalle, Kals, Mart, Luo, Shuang, Padmanabhuni, Shanmukha Sampath, Niemi, Marianna, Gracia-Tabuenca, Javier, Helminen, Mika, Luukkaala, Tiina, Vähätalo, Iida, Tammerluoto, Jyrki, Smith, Sarah, Southerington, Tom, Lehto, Petri, Youssef, Omar, Zidi-Mouaffak, Yossra H.S., and Tamlander, Max

Published
2024
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9. The quantum group dual of the first-row subcategory for the generic Virasoro VOA

Author

Koshida, Shinji and Kytölä, Kalle

Subjects
Mathematics - Quantum Algebra, Mathematical Physics, Mathematics - Representation Theory, 17B69, 17B37, 81T40
Abstract

In several examples it has been observed that a module category of a vertex operator algebra (VOA) is equivalent to a category of representations of some quantum group. The present article is concerned with developing such a duality in the case of the Virasoro VOA at generic central charge; arguably the most rudimentary of all VOAs, yet structurally complicated. We do not address the category of all modules of the generic Virasoro VOA, but we consider the infinitely many modules from the first row of the Kac table. Building on an explicit quantum group method of Coulomb gas integrals, we give a new proof of the fusion rules, we prove the analyticity of compositions of intertwining operators, and we show that the conformal blocks are fully determined by the quantum group method. Crucially, we prove the associativity of the intertwining operators among the first-row modules, and find that the associativity is governed by the $6j$-symbols of the quantum group. Our results constitute a concrete duality between a VOA and a quantum group, and they will serve as the key tools to establish the equivalence of the first-row subcategory of modules of the generic Virasoro VOA and the category of (type-1) finite-dimensional representations of $\mathcal{U}_{q}(\mathfrak{sl}_{2})$., Comment: 79 pages. Accepted for publication in Communications in Mathematical Physics

Published
2021
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11. Ex vivo venetoclax sensitivity predicts clinical response in acute myeloid leukemia in the prospective VenEx trial

Author

Kytölä, Sari, Vänttinen, Ida, Ruokoranta, Tanja, Partanen, Anu, Holopainen, Annasofia, Saad, Joseph, Kuusisto, Milla E. L., Koskela, Sirpa, Räty, Riikka, Itälä-Remes, Maija, Västrik, Imre, Suvela, Minna, Parsons, Alun, Porkka, Kimmo, Wennerberg, Krister, Heckman, Caroline A., Jalkanen, Tero, Huttunen, Teppo, Ettala, Pia, Rimpiläinen, Johanna, Siitonen, Timo, Pyörälä, Marja, Kuusanmäki, Heikki, and Kontro, Mika

Published
2024
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13. Slit-strip Ising boundary conformal field theory 1: Discrete and continuous function spaces

Author

Ameen, Taha, Kytölä, Kalle, Park, S. C., and Radnell, David

Subjects
Mathematical Physics
Abstract

This is the first in a series of articles about recovering the full algebraic structure of a boundary conformal field theory (CFT) from the scaling limit of the critical Ising model in slit-strip geometry. Here, we introduce spaces of holomorphic functions in continuum domains as well as corresponding spaces of discrete holomorphic functions in lattice domains. We find distinguished sets of functions characterized by their singular behavior in the three infinite directions in the slit-strip domains. We prove convergence results of the distinguished discrete holomorphic functions to the continuum ones. In the subsequent articles, the discrete holomorphic functions will be used for the calculation of the Ising model fusion coefficients (as well as for the diagonalization of the Ising transfer matrix), and the convergence of the functions is used to prove the convergence of the fusion coefficients. It will also be shown that the vertex operator algebra of the boundary conformal field theory can be recovered from the limit of the fusion coefficients via geometric transformations involving the distinguished continuum functions., Comment: v3: 50 pages, minor modifications and corrections

Published
2020

14. Diagnostic yield of genetic testing in a multinational heterogeneous cohort of 2088 DCM patients

Author

Krista Heliö, Marcos Cicerchia, Julie Hathaway, Johanna Tommiska, Johanna Huusko, Inka Saarinen, Lotta Koskinen, Mikko Muona, Ville Kytölä, Janica Djupsjöbacka, Massimiliano Gentile, Pertteli Salmenperä, Tero-Pekka Alastalo, Christian Steinberg, Tiina Heliö, Jussi Paananen, Samuel Myllykangas, and Juha Koskenvuo

Subjects
dilated cardiomyopathy, cardiomyopathy, genetic testing, next generation sequencing, diagnostic yield, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

BackgroundFamilial dilated cardiomyopathy (DCM) causes heart failure and may lead to heart transplantation. DCM is typically a monogenic disorder with autosomal dominant inheritance. Currently disease-causing variants have been reported in over 60 genes that encode proteins in sarcomeres, nuclear lamina, desmosomes, cytoskeleton, and mitochondria. Over half of the patients undergoing comprehensive genetic testing are left without a molecular diagnosis even when patient selection follows strict DCM criteria.Methods and resultsThis study was a retrospective review of patients referred for genetic testing at Blueprint Genetics due to suspected inherited DCM. Next generation sequencing panels included 23–316 genes associated with cardiomyopathies and other monogenic cardiac diseases. Variants were considered diagnostic if classified as pathogenic (P) or likely pathogenic (LP). Of the 2,088 patients 514 (24.6%) obtained a molecular diagnosis; 534 LP/P variants were observed across 45 genes, 2.7% (14/514) had two diagnostic variants in dominant genes. Nine copy number variants were identified: two multigene and seven intragenic. Diagnostic variants were observed most often in TTN (45.3%), DSP (6.7%), LMNA (6.7%), and MYH7 (5.2%). Clinical characteristics independently associated with molecular diagnosis were: a lower age at diagnosis, family history of DCM, paroxysmal atrial fibrillation, absence of left bundle branch block, and the presence of an implantable cardioverter-defibrillator.ConclusionsPanel testing provides good diagnostic yield in patients with clinically suspected DCM. Causative variants were identified in 45 genes. In minority, two diagnostic variants were observed in dominant genes. Our results support the use of genetic panels in clinical settings in DCM patients with suspected genetic etiology.

Published
2023
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15. The public health impact of poor sleep on severe COVID-19, influenza and upper respiratory infections

Author

Palotie, Aarno, Daly, Mark, Riley-Gills, Bridget, Jacob, Howard, Paul, Dirk, Petrovski, Slavé, Runz, Heiko, John, Sally, Okafo, George, Lawless, Nathan, Salminen-Mankonen, Heli, Plenge, Robert, Maranville, Joseph, McCarthy, Mark, Ehm, Margaret G., Auro, Kirsi, Longerich, Simonne, Mälarstig, Anders, Klinger, Katherine, Chatelain, Clement, Gossel, Matthias, Estrada, Karol, Graham, Robert, Yang, Robert, O´Donnell, Chris, Mäkelä, Tomi P., Kaprio, Jaakko, Virolainen, Petri, Hakanen, Antti, Kilpi, Terhi, Perola, Markus, Partanen, Jukka, Pitkäranta, Anne, Raivio, Taneli, Tikkanen, Jani, Serpi, Raisa, Laitinen, Tarja, Kosma, Veli-Matti, Laukkanen, Jari, Hautalahti, Marco, Tuovila, Outi, Pakkanen, Raimo, Waring, Jeffrey, Riley-Gillis, Bridget, Rahimov, Fedik, Tachmazidou, Ioanna, Chen, Chia-Yen, Ding, Zhihao, Jung, Marc, Biswas, Shameek, Pendergrass, Rion, Pulford, David, Raghavan, Neha, Huertas-Vazquez, Adriana, Sul, Jae-Hoon, Hu, Xinli, Hedman, Åsa, Rivas, Manuel, Waterworth, Dawn, Renaud, Nicole, Obeidat, Ma´en, Ripatti, Samuli, Schleutker, Johanna, Arvas, Mikko, Carpén, Olli, Hinttala, Reetta, Kettunen, Johannes, Mannermaa, Arto, Aalto-Setälä, Katriina, Kähönen, Mika, Mäkelä, Johanna, Kälviäinen, Reetta, Julkunen, Valtteri, Soininen, Hilkka, Remes, Anne, Hiltunen, Mikko, Peltola, Jukka, Raivio, Minna, Tienari, Pentti, Rinne, Juha, Kallionpää, Roosa, Partanen, Juulia, Abbasi, Ali, Ziemann, Adam, Smaoui, Nizar, Lehtonen, Anne, Eaton, Susan, Lahdenperä, Sanni, Bowers, Natalie, Teng, Edmond, Xu, Fanli, Addis, Laura, Eicher, John, Li, Qingqin S., He, Karen, Khramtsova, Ekaterina, Färkkilä, Martti, Koskela, Jukka, Pikkarainen, Sampsa, Jussila, Airi, Kaukinen, Katri, Blomster, Timo, Kiviniemi, Mikko, Voutilainen, Markku, Lu, Tim, McCarthy, Linda, Hart, Amy, Guan, Meijian, Miller, Jason, Kalpala, Kirsi, Miller, Melissa, Eklund, Kari, Palomäki, Antti, Isomäki, Pia, Pirilä, Laura, Kaipiainen-Seppänen, Oili, Huhtakangas, Johanna, Mars, Nina, Lertratanakul, Apinya, Viollet, Coralie, Hochfeld, Marla, Gordillo, Jorge Esparza, Farias, Fabiana, Bing, Nan, Pelkonen, Margit, Kauppi, Paula, Kankaanranta, Hannu, Harju, Terttu, Lahesmaa, Riitta, Chen, Hubert, Betts, Joanna, Mishra, Rajashree, Mouded, Majd, Ngo, Debby, Niiranen, Teemu, Vaura, Felix, Salomaa, Veikko, Metsärinne, Kaj, Aittokallio, Jenni, Hernesniemi, Jussi, Gordin, Daniel, Sinisalo, Juha, Taskinen, Marja-Riitta, Tuomi, Tiinamaija, Hiltunen, Timo, Elliott, Amanda, Reeve, Mary Pat, Ruotsalainen, Sanni, Chu, Audrey, Reilly, Dermot, Mendelson, Mike, Parkkinen, Jaakko, Meretoja, Tuomo, Joensuu, Heikki, Mattson, Johanna, Salminen, Eveliina, Auranen, Annika, Karihtala, Peeter, Auvinen, Päivi, Elenius, Klaus, Pitkänen, Esa, Popovic, Relja, Fabre, Margarete, Schutzman, Jennifer, Kulkarni, Diptee, Porello, Alessandro, Loboda, Andrey, Lehtonen, Heli, McDonough, Stefan, Vuoti, Sauli, Kaarniranta, Kai, Turunen, Joni A., Ollila, Terhi, Uusitalo, Hannu, Karjalainen, Juha, Liu, Mengzhen, Loomis, Stephanie, Strauss, Erich, Chen, Hao, Tasanen, Kaisa, Huilaja, Laura, Hannula-Jouppi, Katariina, Salmi, Teea, Peltonen, Sirkku, Koulu, Leena, Choy, David, Wu, Ying, Pussinen, Pirkko, Salminen, Aino, Salo, Tuula, Rice, David, Nieminen, Pekka, Palotie, Ulla, Siponen, Maria, Suominen, Liisa, Mäntylä, Päivi, Gursoy, Ulvi, Anttonen, Vuokko, Sipilä, Kirsi, Laivuori, Hannele, Kurra, Venla, Kotaniemi-Talonen, Laura, Heikinheimo, Oskari, Kalliala, Ilkka, Aaltonen, Lauri, Jokimaa, Varpu, Vääräsmäki, Marja, Uimari, Outi, Morin-Papunen, Laure, Niinimäki, Maarit, Piltonen, Terhi, Kivinen, Katja, Widen, Elisabeth, Tukiainen, Taru, Välimäki, Niko, Laakkonen, Eija, Tyrmi, Jaakko, Silven, Heidi, Sliz, Eeva, Arffman, Riikka, Savukoski, Susanna, Laisk, Triin, Pujol, Natalia, Kumar, Janet, Hovatta, Iiris, Isometsä, Erkki, Ollila, Hanna, Suvisaari, Jaana, Als, Thomas Damm, Mäkitie, Antti, Bizaki-Vallaskangas, Argyro, Toppila-Salmi, Sanna, Willberg, Tytti, Saarentaus, Elmo, Aarnisalo, Antti, Rahikkala, Elisa, Aittomäki, Kristiina, Åberg, Fredrik, Kurki, Mitja, Havulinna, Aki, Mehtonen, Juha, Palta, Priit, Hassan, Shabbeer, Della Briotta Parolo, Pietro, Zhou, Wei, Maasha, Mutaamba, Lemmelä, Susanna, Liu, Aoxing, Lehisto, Arto, Ganna, Andrea, Llorens, Vincent, Heyne, Henrike, Rämö, Joel, Rodosthenous, Rodos, Strausz, Satu, Palotie, Tuula, Palin, Kimmo, Garcia-Tabuenca, Javier, Siirtola, Harri, Kiiskinen, Tuomo, Lee, Jiwoo, Tsuo, Kristin, Kristiansson, Kati, Hyvärinen, Kati, Ritari, Jarmo, Pylkäs, Katri, Karjalainen, Minna, Mantere, Tuomo, Kangasniemi, Eeva, Heikkinen, Sami, Pitkänen, Nina, Lessard, Samuel, Chatelain, Clément, Kallio, Lila, Wahlfors, Tiina, Punkka, Eero, Siltanen, Sanna, Kuopio, Teijo, Jalanko, Anu, Shen, Huei-Yi, Kajanne, Risto, Aavikko, Mervi, Leinonen, Rasko, Palin, Henna, Linna, Malla-Maria, Kanai, Masahiro, Zheng, Zhili, Lahtela, L. Elisa, Kaunisto, Mari, Kilpeläinen, Elina, Sipilä, Timo P., Dada, Oluwaseun Alexander, Ghazal, Awaisa, Kytölä, Anastasia, Weldatsadik, Rigbe, Donner, Kati, Loukola, Anu, Laiho, Päivi, Sistonen, Tuuli, Kaiharju, Essi, Laukkanen, Markku, Järvensivu, Elina, Lähteenmäki, Sini, Männikkö, Lotta, Wong, Regis, Toivola, Auli, Brunfeldt, Minna, Mattsson, Hannele, Koskelainen, Sami, Hiekkalinna, Tero, Paajanen, Teemu, Pärn, Kalle, Kals, Mart, Luo, Shuang, Padmanabhuni, Shanmukha Sampath, Niemi, Marianna, Gracia-Tabuenca, Javier, Helminen, Mika, Luukkaala, Tiina, Vähätalo, Iida, Tammerluoto, Jyrki, Smith, Sarah, Southerington, Tom, Lehto, Petri, Jones, Samuel E., Maisha, Fahrisa I., Strausz, Satu J., Lammi, Vilma, Cade, Brian E., Tervi, Anniina, Helaakoski, Viola, Broberg, Martin E., Lane, Jacqueline M., Redline, Susan, Saxena, Richa, and Ollila, Hanna M.

Published
2023
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16. Longitudinal Metabolome-Wide Signals Prior to the Appearance of a First Islet Autoantibody in Children Participating in the TEDDY Study

Author

Li, Qian, Parikh, Hemang, Butterworth, Martha D, Lernmark, Åke, Hagopian, William, Rewers, Marian, She, Jin-Xiong, Toppari, Jorma, Ziegler, Anette-G, Akolkar, Beena, Fiehn, Oliver, Fan, Sili, Krischer, Jeffrey P, Barbour, Aaron, Bautista, Kimberly, Baxter, Judith, Felipe-Morales, Daniel, Driscoll, Kimberly, Frohnert, Brigitte I, Stahl, Marisa, Gesualdo, Patricia, Hoffman, Michelle, Karban, Rachel, Liu, Edwin, Norris, Jill, Peacock, Stesha, Shorrosh, Hanan, Steck, Andrea, Stern, Megan, Villegas, Erica, Waugh, Kathleen, Simell, Olli G, Adamsson, Annika, Ahonen, Suvi, Åkerlund, Mari, Hakola, Leena, Hekkala, Anne, Holappa, Henna, Hyöty, Heikki, Ikonen, Anni, Ilonen, Jorma, Jäminki, Sinikka, Jokipuu, Sanna, Karlsson, Leena, Kero, Jukka, Kähönen, Miia, Knip, Mikael, Koivikko, Minna-Liisa, Koskinen, Merja, Koreasalo, Mirva, Kurppa, Kalle, Kytölä, Jarita, Latva-aho, Tiina, Lindfors, Katri, Lönnrot, Maria, Mäntymäki, Elina, Mattila, Markus, Miettinen, Maija, Multasuo, Katja, Mykkänen, Teija, Niininen, Tiina, Niinistö, Sari, Nyblom, Mia, Oikarinen, Sami, Ollikainen, Paula, Othmani, Zhian, Pohjola, Sirpa, Rajala, Petra, Rautanen, Jenna, Riikonen, Anne, Riski, Eija, Pekkola, Miia, Romo, Minna, Ruohonen, Satu, Simell, Satu, Sjöberg, Maija, Stenius, Aino, Tossavainen, Päivi, Vähä-Mäkilä, Mari, Vainionpää, Sini, Varjonen, Eeva, Veijola, Riitta, Viinikangas, Irene, Virtanen, Suvi M, Schatz, Desmond, Hopkins, Diane, Steed, Leigh, Bryant, Jennifer, Silvis, Katherine, Haller, Michael, Gardiner, Melissa, McIndoe, Richard, Sharma, Ashok, Anderson, Stephen W, Jacobsen, Laura, Marks, John, and Towe, PD

Subjects
Pediatric, Autoimmune Disease, Diabetes, Prevention, Nutrition, Metabolic and endocrine, Alanine, Amino Acids, Branched-Chain, Autoantibodies, Child, Preschool, Dehydroascorbic Acid, Diabetes Mellitus, Type 1, Fatty Acids, Female, Genetic Predisposition to Disease, Glutamate Decarboxylase, Humans, Infant, Infant, Newborn, Insulin Antibodies, Longitudinal Studies, Male, Metabolome, Methionine, Phosphatidylethanolamines, Prodromal Symptoms, Proline, Risk, Triglycerides, gamma-Aminobutyric Acid, TEDDY Study Group, Medical and Health Sciences, Endocrinology & Metabolism
Abstract

Children at increased genetic risk for type 1 diabetes (T1D) after environmental exposures may develop pancreatic islet autoantibodies (IA) at a very young age. Metabolic profile changes over time may imply responses to exposures and signal development of the first IA. Our present research in The Environmental Determinants of Diabetes in the Young (TEDDY) study aimed to identify metabolome-wide signals preceding the first IA against GAD (GADA-first) or against insulin (IAA-first). We profiled metabolomes by mass spectrometry from children's plasma at 3-month intervals after birth until appearance of the first IA. A trajectory analysis discovered each first IA preceded by reduced amino acid proline and branched-chain amino acids (BCAAs), respectively. With independent time point analysis following birth, we discovered dehydroascorbic acid (DHAA) contributing to the risk of each first IA, and γ-aminobutyric acid (GABAs) associated with the first autoantibody against insulin (IAA-first). Methionine and alanine, compounds produced in BCAA metabolism and fatty acids, also preceded IA at different time points. Unsaturated triglycerides and phosphatidylethanolamines decreased in abundance before appearance of either autoantibody. Our findings suggest that IAA-first and GADA-first are heralded by different patterns of DHAA, GABA, multiple amino acids, and fatty acids, which may be important to primary prevention of T1D.

Published
2020

18. Resectability, conversion, metastasectomy and outcome according to RAS and BRAF status for metastatic colorectal cancer in the prospective RAXO study

Author

Uutela, Aki, Osterlund, Emerik, Halonen, Päivi, Kallio, Raija, Ålgars, Annika, Salminen, Tapio, Lamminmäki, Annamarja, Soveri, Leena-Maija, Ristamäki, Raija, Lehtomäki, Kaisa, Stedt, Hanna, Heervä, Eetu, Muhonen, Timo, Kononen, Juha, Nordin, Arno, Ovissi, Ali, Kytölä, Soili, Keinänen, Mauri, Sundström, Jari, Nieminen, Lasse, Mäkinen, Markus J., Kuopio, Teijo, Ristimäki, Ari, Isoniemi, Helena, and Osterlund, Pia

Published
2022
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20. Whole-exome sequencing identifies novel protein-altering variants associated with serum apolipoprotein and lipid concentrations

Author

Niina Sandholm, Ronja Hotakainen, Jani K. Haukka, Fanny Jansson Sigfrids, Emma H. Dahlström, Anni A. Antikainen, Erkka Valo, Anna Syreeni, Elina Kilpeläinen, Anastasia Kytölä, Aarno Palotie, Valma Harjutsalo, Carol Forsblom, Per-Henrik Groop, and on behalf of the FinnDiane Study Group

Subjects
Apolipoprotein A1, Apolipoprotein C-III, Whole-exome sequencing, Lipidomics, LIPC, APOB, Medicine, Genetics, QH426-470
Abstract

Abstract Background Dyslipidemia is a major risk factor for cardiovascular disease, and diabetes impacts the lipid metabolism through multiple pathways. In addition to the standard lipid measurements, apolipoprotein concentrations provide added awareness of the burden of circulating lipoproteins. While common genetic variants modestly affect the serum lipid concentrations, rare genetic mutations can cause monogenic forms of hypercholesterolemia and other genetic disorders of lipid metabolism. We aimed to identify low-frequency protein-altering variants (PAVs) affecting lipoprotein and lipid traits. Methods We analyzed whole-exome (WES) and whole-genome sequencing (WGS) data of 481 and 474 individuals with type 1 diabetes, respectively. The phenotypic data consisted of 79 serum lipid and apolipoprotein phenotypes obtained with clinical laboratory measurements and nuclear magnetic resonance spectroscopy. Results The single-variant analysis identified an association between the LIPC p.Thr405Met (rs113298164) and serum apolipoprotein A1 concentrations (p=7.8×10−8). The burden of PAVs was significantly associated with lipid phenotypes in LIPC, RBM47, TRMT5, GTF3C5, MARCHF10, and RYR3 (p170,000 individuals from multiple ancestries (p=0.0013). Two PAVs in GTF3C5 were highly enriched in the Finnish population and associated with cardiovascular phenotypes in the general population. In the previously known APOB gene, we identified novel associations at two protein-truncating variants resulting in lower serum non-HDL cholesterol (p=4.8×10−4), apolipoprotein B (p=5.6×10−4), and LDL cholesterol (p=9.5×10−4) concentrations. Conclusions We identified lipid and apolipoprotein-associated variants in the previously known LIPC and APOB genes, as well as PAVs in GTF3C5 associated with LDLC, and in RBM47 associated with apolipoprotein C-III concentrations, implicated as an independent CVD risk factor. Identification of rare loss-of-function variants has previously revealed genes that can be targeted to prevent CVD, such as the LDL cholesterol-lowering loss-of-function variants in the PCSK9 gene. Thus, this study suggests novel putative therapeutic targets for the prevention of CVD.

Published
2022
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21. P409: BCL-2/BCL-XL INHIBITION INDUCES APOPTOSIS AND CIRCUMVENTS VENETOCLAX RESISTANCE IN TP53-MUTATED ACUTE MYELOID LEUKEMIA

Author

Ida Vänttinen, Sari Kytölä, Olli Dufva, Monica Hellesøy, Stein-Erik Gullaksen, Tanja Ruokoranta, Oscar Brück, Sanna Siitonen, Pia Ettala, Marja Pyörälä, Johanna Rimpilainen, Timo Siitonen, Bjorn Tore Gjertsen, Caroline Heckman, Heikki Kuusanmäki, and Mika Kontro

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Published
2023
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22. P562: CAPILLARY BLOOD SAMPLING ALLOWS FEASIBLE METHOD FOR VENETOCLAX CONCENTRATION MEASUREMENT IN AN ACADEMIC MULTICENTER CLINICAL TRIAL CONTEXT

Author

Sari Kytölä, Ida Vänttinen, Heikki Kuusanmäki, Tanja Ruokoranta, Mika Kurkela, Johanna Kiiski, Annasofia Holopainen, Anu Partanen, Milla E.L. Kuusisto, Sirpa Koskela, Riikka Räty, Maija Itälä-Remes, Pia Ettala, Johanna Rimpiläinen, Timo Siitonen, Marja Pyörälä, Janne T. Backman, Mikko Niemi, and Mika Kontro

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Published
2023
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23. Risk of Midlife Stroke After Adverse Pregnancy Outcomes: The FinnGen Study

Author

Miller, Eliza C., Kauko, Anni, Tom, Sarah E., Laivuori, Hannele, Niiranen, Teemu, Bello, Natalie A., Palotie, Aarno, Daly, Mark, Riley-Gills, Bridget, Jacob, Howard, Paul, Dirk, Matakidou, Athena, Platt, Adam, Runz, Heiko, John, Sally, Okafo, George, Lawless, Nathan, Salminen-Mankonen, Heli, Plenge, Robert, Maranville, Joseph, McCarthy, Mark, Hunkapiller, Julie, Ehm, Margaret G., Auro, Kirsi, Longerich, Simonne, Fox, Caroline, Mälarstig, Anders, Klinger, Katherine, Raipal, Deepak, Green, Eric, Graham, Robert, Yang, Robert, Donnell, Chris O´, Mäkelä, Tomi P., Kaprio, Jaakko, Virolainen, Petri, Hakanen, Antti, Kilpi, Terhi, Perola, Markus, Partanen, Jukka, Pitkäranta, Anne, Raivio, Taneli, Serpi, Raisa, Laitinen, Tarja, Kosma, Veli-Matti, Laukkanen, Jari, Hautalahti, Marco, Tuovila, Outi, Pakkanen, Raimo, Waring, Jeffrey, Riley-Gillis, Bridget, Rahimov, Fedik, Tachmazidou, Ioanna, Chen, Chia-Yen, Runz, Heiko, Ding, Zhihao, Jung, Marc, Biswas, Shameek, Pendergrass, Rion, Hunkapiller, Julie, Ehm, Margaret G., Pulford, David, Raghavan, Neha, Huertas-Vazquez, Adriana, Sul, Jae-Hoon, Mälarstig, Anders, Hu, Xinli, Klinger, Katherine, Graham, Robert, Green, Eric, Mozaffari, Sahar, Waterworth, Dawn, Renaud, Nicole, Obeidat, Ma´en, Ripatti, Samuli, Schleutker, Johanna, Perola, Markus, Arvas, Mikko, Carpén, Olli, Hinttala, Reetta, Kettunen, Johannes, Mannermaa, Arto, Aalto-Setälä, Katriina, Kähönen, Mika, Laukkanen, Jari, Mäkelä, Johanna, Kälviäinen, Reetta, Julkunen, Valtteri, Soininen, Hilkka, Remes, Anne, Hiltunen, Mikko, Peltola, Jukka, Raivio, Minna, Tienari, Pentti, Rinne, Juha, Kallionpää, Roosa, Partanen, Juulia, Abbasi, Ali, Ziemann, Adam, Smaoui, Nizar, Lehtonen, Anne, Eaton, Susan, Runz, Heiko, Lahdenperä, Sanni, Biswas, Shameek, Hunkapiller, Julie, Bowers, Natalie, Teng, Edmond, Pendergrass, Rion, Xu, Fanli, Pulford, David, Auro, Kirsi, Addis, Laura, Eicher, John, Li, Qingqin S, He, Karen, Khramtsova, Ekaterina, Raghavan, Neha, Färkkilä, Martti, Koskela, Jukka, Pikkarainen, Sampsa, Jussila, Airi, Kaukinen, Katri, Blomster, Timo, Kiviniemi, Mikko, Voutilainen, Markku, Daly, Mark, Abbasi, Ali, Waring, Jeffrey, Smaoui, Nizar, Rahimov, Fedik, Lehtonen, Anne, Lu, Tim, Bowers, Natalie, Pendergrass, Rion, McCarthy, Linda, Hart, Amy, Guan, Meijian, Miller, Jason, Kalpala, Kirsi, Miller, Melissa, Hu, Xinli, Eklund, Kari, Palomäki, Antti, Isomäki, Pia, Pirilä, Laura, Kaipiainen-Seppänen, Oili, Huhtakangas, Johanna, Mars, Nina, Abbasi, Ali, Waring, Jeffrey, Rahimov, Fedik, Lertratanakul, Apinya, Smaoui, Nizar, Lehtonen, Anne, Hochfeld, Marla, Bowers, Natalie, Pendergrass, Rion, Esparza Gordillo, Jorge, Auro, Kirsi, Waterworth, Dawn, Farias, Fabiana, Kalpala, Kirsi, Bing, Nan, Hu, Xinli, Laitinen, Tarja, Pelkonen, Margit, Kauppi, Paula, Kankaanranta, Hannu, Harju, Terttu, Lahesmaa, Riitta, Smaoui, Nizar, Lassi, Glenda, Eaton, Susan, Chen, Hubert, Pendergrass, Rion, Bowers, Natalie, Betts, Joanna, Auro, Kirsi, Mishra, Rajashree, Mouded, Majd, Ngo, Debby, Vaura, Felix, Salomaa, Veikko, Metsärinne, Kaj, Aittokallio, Jenni, Kähönen, Mika, Hernesniemi, Jussi, Gordin, Daniel, Sinisalo, Juha, Taskinen, Marja-Riitta, Tuomi, Tiinamaija, Hiltunen, Timo, Laukkanen, Jari, Elliott, Amanda, Pat Reeve, Mary, Ruotsalainen, Sanni, Challis, Benjamin, Paul, Dirk, Hunkapiller, Julie, Bowers, Natalie, Pendergrass, Rion, Chu, Audrey, Auro, Kirsi, Reilly, Dermot, Mendelson, Mike, Parkkinen, Jaakko, Miller, Melissa, Meretoja, Tuomo, Joensuu, Heikki, Carpén, Olli, Mattson, Johanna, Salminen, Eveliina, Auranen, Annika, Karihtala, Peeter, Elenius, Päivi Auvinen Klaus, Schleutker, Johanna, Pitkänen, Esa, Mars, Nina, Daly, Mark, Popovic, Relja, Waring, Jeffrey, Riley-Gillis, Bridget, Lehtonen, Anne, Schutzman, Jennifer, Hunkapiller, Julie, Bowers, Natalie, Pendergrass, Rion, Kulkarni, Diptee, Auro, Kirsi, Porello, Alessandro, Loboda, Andrey, Lehtonen, Heli, McDonough, Stefan, Vuoti, Sauli, Kaarniranta, Kai, Turunen, Joni A, Ollila, Terhi, Uusitalo, Hannu, Karjalainen, Juha, Pitkänen, Esa, Liu, Mengzhen, Runz, Heiko, Loomis, Stephanie, Strauss, Erich, Bowers, Natalie, Chen, Hao, Pendergrass, Rion, Tasanen, Kaisa, Huilaja, Laura, Hannula-Jouppi, Katariina, Salmi, Teea, Peltonen, Sirkku, Koulu, Leena, Smaoui, Nizar, Rahimov, Fedik, Lehtonen, Anne, Choy, David, Pendergrass, Rion, Waterworth, Dawn, Kalpala, Kirsi, Wu, Ying, Pussinen, Pirkko, Salminen, Aino, Salo, Tuula, Rice, David, Nieminen, Pekka, Palotie, Ulla, Siponen, Maria, Suominen, Liisa, Mäntylä, Päivi, Gursoy, Ulvi, Anttonen, Vuokko, Sipilä, Kirsi, Pendergrass, Rion, Kurra, Venla, Kotaniemi-Talonen, Laura, Heikinheimo, Oskari, Kalliala, Ilkka, Aaltonen, Lauri, Jokimaa, Varpu, Kettunen, Johannes, Vääräsmäki, Marja, Uimari, Outi, Morin-Papunen, Laure, Niinimäki, Maarit, Piltonen, Terhi, Kivinen, Katja, Widen, Elisabeth, Tukiainen, Taru, Pat Reeve, Mary, Daly, Mark, Välimäki, Niko, Laakkonen, Eija, Tyrmi, Jaakko, Silven, Heidi, Sliz, Eeva, Arffman, Riikka, Savukoski, Susanna, Laisk, Triin, Pujol, Natalia, Liu, Mengzhen, Riley-Gillis, Bridget, Pendergrass, Rion, Kumar, Janet, Auro, Kirsi, Hovatta, Iiris, Chen, Chia-Yen, Isometsä, Erkki, Ollila, Hanna, Suvisaari, Jaana, Damm Als, Thomas, Mäkitie, Antti, Bizaki-Vallaskangas, Argyro, Toppila-Salmi, Sanna, Willberg, Tytti, Saarentaus, Elmo, Aarnisalo, Antti, Salminen, Eveliina, Rahikkala, Elisa, Kettunen, Johannes, Aittomäki, Kristiina, Åberg, Fredrik, Kurki, Mitja, Ripatti, Samuli, Daly, Mark, Karjalainen, Juha, Havulinna, Aki, Mehtonen, Juha, Palta, Priit, Hassan, Shabbeer, Della, Pietro, Parolo, Briotta, Zhou, Wei, Maasha, Mutaamba, Hassan, Shabbeer, Lemmelä, Susanna, Rivas, Manuel, Niemi, Mari E., Palotie, Aarno, Liu, Aoxing, Lehisto, Arto, Ganna, Andrea, Llorens, Vincent, Tukiainen, Taru, Pat Reeve, Mary, Heyne, Henrike, Mars, Nina, Rämö, Joel, Saarentaus, Elmo, Ollila, Hanna, Rodosthenous, Rodos, Strausz, Satu, Palotie, Tuula, Palin, Kimmo, Garcia-Tabuenca, Javier, Siirtola, Harri, Kiiskinen, Tuomo, Lee, Jiwoo, Tsuo, Kristin, Elliott, Amanda, Kristiansson, Kati, Arvas, Mikko, Hyvärinen, Kati, Ritari, Jarmo, Carpén, Olli, Kettunen, Johannes, Pylkäs, Katri, Sliz, Eeva, Karjalainen, Minna, Mantere, Tuomo, Kangasniemi, Eeva, Heikkinen, Sami, Mannermaa, Arto, Laakkonen, Eija, Pitkänen, Nina, Lessard, Samuel, Chatelain, Clément, Terho, Perttu, Soini, Sirpa, Partanen, Jukka, Punkka, Eero, Serpi, Raisa, Siltanen, Sanna, Kosma, Veli-Matti, Kuopio, Teijo, Jalanko, Anu, Shen, Huei-Yi, Kajanne, Risto, Aavikko, Mervi, Palin, Henna, Linna, Malla-Maria, Kurki, Mitja, Karjalainen, Juha, Della, Pietro, Parolo, Briotta, Lehisto, Arto, Mehtonen, Juha, Zhou, Wei, Kanai, Masahiro, Maasha, Mutaamba, Havulinna, Aki, Lemmelä, Susanna, Kiiskinen, Tuomo, Elisa Lahtela, L., Kaunisto, Mari, Kilpeläinen, Elina, Sipilä, Timo P., Alexander Dada, Oluwaseun, Ghazal, Awaisa, Kytölä, Anastasia, Weldatsadik, Rigbe, Ruotsalainen, Sanni, Donner, Kati, Sipilä, Timo P., Loukola, Anu, Laiho, Päivi, Sistonen, Tuuli, Kaiharju, Essi, Laukkanen, Markku, Järvensivu, Elina, Lähteenmäki, Sini, Männikkö, Lotta, Wong, Regis, Toivola, Auli, Brunfeldt, Minna, Mattsson, Hannele, Kristiansson, Kati, Lemmelä, Susanna, Koskelainen, Sami, Hiekkalinna, Tero, Paajanen, Teemu, Palta, Priit, Pärn, Kalle, Kals, Mart, Luo, Shuang, Laitinen, Tarja, Pat Reeve, Mary, Sampath Padmanabhuni, Shanmukha, Niemi, Marianna, Siirtola, Harri, Gracia-Tabuenca, Javier, Helminen, Mika, Luukkaala, Tiina, Vähätalo, Iida, Pitkänen, Jyrki, Hautalahti, Marco, Mäkelä, Johanna, Smith, Sarah, and Southerington, Tom

Published
2023
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28. Epigenetic modifier gene mutations in chronic myeloid leukemia (CML) at diagnosis are associated with risk of relapse upon treatment discontinuation

Author

Shady Adnan Awad, Oscar Brück, Naranie Shanmuganathan, Timo Jarvinen, Hanna Lähteenmäki, Jay Klievink, Hazem Ibrahim, Soili Kytölä, Perttu Koskenvesa, Timothy P. Hughes, Susan Branford, Matti Kankainen, and Satu Mustjoki

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Published
2022
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29. Conformal blocks, $q$-combinatorics, and quantum group symmetry

Author

Karrila, Alex, Kytölä, Kalle, and Peltola, Eveliina

Subjects
Mathematical Physics, Primary: 81T40. Secondary: 05B20, 16T05, 60D05
Abstract

In this article, we find a $q$-analogue for Fomin's formulas. The original Fomin's formulas relate determinants of random walk excursion kernels to loop-erased random walk partition functions, and our formulas analogously relate conformal block functions of conformal field theories to pure partition functions of multiple SLE random curves. We also provide a construction of the conformal block functions by a method based on a quantum group, the $q$-deformation of $\mathfrak{sl}_2$. The construction both highlights the representation theoretic origin of conformal block functions and explains the appearance of $q$-combinatorial formulas., Comment: 24 pages, 7 figures. v3: minor improvements. Accepted for publication in Annales de l'Institut Henri Poincar\'e D

Published
2017
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30. Boundary correlations in planar LERW and UST

Author

Karrila, Alex, Kytölä, Kalle, and Peltola, Eveliina

Subjects
Mathematical Physics, Mathematics - Combinatorics, Mathematics - Probability, 60Dxx, 81T40, 35Q99, 05B20
Abstract

We find explicit formulas for the probabilities of general boundary visit events for planar loop-erased random walks, as well as connectivity events for branches in the uniform spanning tree. We show that both probabilities, when suitably renormalized, converge in the scaling limit to conformally covariant functions which satisfy partial differential equations of second and third order, as predicted by conformal field theory. The scaling limit connectivity probabilities also provide formulas for the pure partition functions of multiple $\mathrm{SLE}_\kappa$ at $\kappa=2$., Comment: 72 pages, 46 figures; Final version, accepted for publication in Comm. Math. Phys

Published
2017
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32. P487: Genetic findings from multi-gene panel for primary ciliary dyskinesia

Author

Victoria Howell, Johanna Huusko, Manuel Bernal, Allison Faber, Satu Valo, Kimberly Gall, Lotta Koskinen, Tiia Kangas-Kontio, Inka Saarinen, Ville Kytölä, Pauli Siivonen, Janica Djupsjöbacka, Massimiliano Gentile, Pertteli Salmenperä, Jussi Paananen, Samuel Myllykangas, and Juha Koskenvuo

Subjects
Genetics, QH426-470, Medicine
Published
2023
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34. Ex vivo venetoclax sensitivity testing predicts treatment response in acute myeloid leukemia

Author

Heikki Kuusanmäki, Sari Kytölä, Ida Vänttinen, Tanja Ruokoranta, Amanda Ranta, Jani Huuhtanen, Minna Suvela, Alun Parsons, Annasofia Holopainen, Anu Partanen, Milla E.L. Kuusisto, Sirpa Koskela, Riikka Räty, Maija Itälä-Remes, Imre Västrik, Olli Dufva, Sanna Siitonen, Kimmo Porkka, Krister Wennerberg, Caroline A. Heckman, Pia Ettala, Marja Pyörälä, Johanna Rimpiläinen, Timo Siitonen, and Mika Kontro

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

The BCL-2 inhibitor venetoclax has revolutionized the treatment of acute myeloid leukemia (AML) in patients not benefiting from intensive chemotherapy. Nevertheless, treatment failure remains a challenge, and predictive markers are needed, particularly for relapsed or refractory AML. Ex vivo drug sensitivity testing may correlate with outcomes, but its prospective predictive value remains unexplored. Here we report the results of the first stage of the prospective phase II VenEx trial evaluating the utility and predictiveness of venetoclax sensitivity testing using different cell culture conditions and cell viability assays in patients receiving venetoclax-azacitidine. Participants with de novo AML ineligible for intensive chemotherapy, relapsed or refractory AML, or secondary AML were included. The primary endpoint was the treatment response in participants showing ex vivo sensitivity and the key secondary endpoints were the correlation of sensitivity with responses and survival. Venetoclax sensitivity testing was successful in 38/39 participants. Experimental conditions significantly influenced the predictive accuracy. Blast-specific venetoclax sensitivity measured in conditioned medium most accurately correlated with treatment outcomes; 88% of sensitive participants achieved a treatment response. The median survival was significantly longer for participants who were ex vivo-sensitive to venetoclax (14.6 months for venetoclax-sensitive patients vs. 3.5 for venetoclax-insensitive patients, P

Published
2022
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35. Comprehensive Inherited Risk Estimation for Risk-Based Breast Cancer Screening in Women

Author

Mars, Nina, primary, Kerminen, Sini, additional, Tamlander, Max, additional, Pirinen, Matti, additional, Jakkula, Eveliina, additional, Aaltonen, Kirsimari, additional, Meretoja, Tuomo, additional, Heinävaara, Sirpa, additional, Widén, Elisabeth, additional, Ripatti, Samuli, additional, Palotie, Aarno, additional, Daly, Mark, additional, Riley-Gills, Bridget, additional, Jacob, Howard, additional, Paul, Dirk, additional, Matakidou, Athena, additional, Platt, Adam, additional, Runz, Heiko, additional, John, Sally, additional, Okafo, George, additional, Lawless, Nathan, additional, Plenge, Robert, additional, Maranville, Joseph, additional, McCarthy, Mark, additional, Hunkapiller, Julie, additional, Ehm, Margaret G., additional, Auro, Kirsi, additional, Longerich, Simonne, additional, Fox, Caroline, additional, Mälarstig, Anders, additional, Klinger, Katherine, additional, Raipal, Deepak, additional, Green, Eric, additional, Graham, Robert, additional, Yang, Robert, additional, O'Donnell, Chris, additional, Mäkelä, Tomi P., additional, Kaprio, Jaakko, additional, Virolainen, Petri, additional, Hakanen, Antti, additional, Kilpi, Terhi, additional, Perola, Markus, additional, Partanen, Jukka, additional, Pitkäranta, Anne, additional, Junttila, Juhani, additional, Serpi, Raisa, additional, Laitinen, Tarja, additional, Kosma, Veli-Matti, additional, Laukkanen, Jari, additional, Hautalahti, Marco, additional, Tuovila, Outi, additional, Pakkanen, Raimo, additional, Waring, Jeffrey, additional, Riley-Gillis, Bridget, additional, Rahimov, Fedik, additional, Tachmazidou, Ioanna, additional, Chen, Chia-Yen, additional, Ding, Zhihao, additional, Jung, Marc, additional, Biswas, Shameek, additional, Pendergrass, Rion, additional, Pulford, David, additional, Raghavan, Neha, additional, Huertas-Vazquez, Adriana, additional, Sul, Jae-Hoon, additional, Hu, Xinli, additional, Mozaffari, Sahar, additional, Waterworth, Dawn, additional, Renaud, Nicole, additional, Obeidat, Ma'en, additional, Schleutker, Johanna, additional, Arvas, Mikko, additional, Carpén, Olli, additional, Hinttala, Reetta, additional, Kettunen, Johannes, additional, Mannermaa, Arto, additional, Aalto-Setälä, Katriina, additional, Kähönen, Mika, additional, Mäkelä, Johanna, additional, Kälviäinen, Reetta, additional, Julkunen, Valtteri, additional, Soininen, Hilkka, additional, Remes, Anne, additional, Hiltunen, Mikko, additional, Peltola, Jukka, additional, Raivio, Minna, additional, Tienari, Pentti, additional, Rinne, Juha, additional, Kallionpää, Roosa, additional, Partanen, Juulia, additional, Abbasi, Ali, additional, Ziemann, Adam, additional, Smaoui, Nizar, additional, Lehtonen, Anne, additional, Eaton, Susan, additional, Lahdenperä, Sanni, additional, Bowers, Natalie, additional, Teng, Edmond, additional, Xu, Fanli, additional, Addis, Laura, additional, Eicher, John, additional, Li, Qingqin S, additional, He, Karen, additional, Khramtsova, Ekaterina, additional, Färkkilä, Martti, additional, Koskela, Jukka, additional, Pikkarainen, Sampsa, additional, Jussila, Airi, additional, Kaukinen, Katri, additional, Blomster, Timo, additional, Kiviniemi, Mikko, additional, Voutilainen, Markku, additional, Lu, Tim, additional, McCarthy, Linda, additional, Hart, Amy, additional, Guan, Meijian, additional, Miller, Jason, additional, Kalpala, Kirsi, additional, Miller, Melissa, additional, Eklund, Kari, additional, Palomäki, Antti, additional, Isomäki, Pia, additional, Pirilä, Laura, additional, Kaipiainen-Seppänen, Oili, additional, Huhtakangas, Johanna, additional, Mars, Nina, additional, Lertratanakul, Apinya, additional, Close, David, additional, Hochfeld, Marla, additional, Gordillo, Jorge Esparza, additional, Farias, Fabiana, additional, Bing, Nan, additional, Pelkonen, Margit, additional, Kauppi, Paula, additional, Kankaanranta, Hannu, additional, Harju, Terttu, additional, Lahesmaa, Riitta, additional, Mackay, Alex, additional, Lassi, Glenda, additional, Chen, Hubert, additional, Betts, Joanna, additional, Mishra, Rajashree, additional, Mouded, Majd, additional, Ngo, Debby, additional, Niiranen, Teemu, additional, Vaura, Felix, additional, Salomaa, Veikko, additional, Metsärinne, Kaj, additional, Aittokallio, Jenni, additional, Hernesniemi, Jussi, additional, Gordin, Daniel, additional, Sinisalo, Juha, additional, Taskinen, Marja-Riitta, additional, Tuomi, Tiinamaija, additional, Hiltunen, Timo, additional, Elliott, Amanda, additional, Reeve, Mary Pat, additional, Ruotsalainen, Sanni, additional, Challis, Benjamin, additional, Chu, Audrey, additional, Reilly, Dermot, additional, Mendelson, Mike, additional, Parkkinen, Jaakko, additional, Joensuu, Heikki, additional, Mattson, Johanna, additional, Salminen, Eveliina, additional, Auranen, Annika, additional, Karihtala, Peeter, additional, Auvinen, Päivi, additional, Elenius, Klaus, additional, Pitkänen, Esa, additional, Popovic, Relja, additional, Schutzman, Jennifer, additional, Kulkarni, Diptee, additional, Porello, Alessandro, additional, Loboda, Andrey, additional, Lehtonen, Heli, additional, McDonough, Stefan, additional, Vuoti, Sauli, additional, Kaarniranta, Kai, additional, Turunen, Joni A, additional, Ollila, Terhi, additional, Uusitalo, Hannu, additional, Karjalainen, Juha, additional, Liu, Mengzhen, additional, Loomis, Stephanie, additional, Strauss, Erich, additional, Chen, Hao, additional, Tasanen, Kaisa, additional, Huilaja, Laura, additional, Hannula-Jouppi, Katariina, additional, Salmi, Teea, additional, Peltonen, Sirkku, additional, Koulu, Leena, additional, Choy, David, additional, Wu, Ying, additional, Pussinen, Pirkko, additional, Salminen, Aino, additional, Salo, Tuula, additional, Rice, David, additional, Nieminen, Pekka, additional, Palotie, Ulla, additional, Siponen, Maria, additional, Suominen, Liisa, additional, Mäntylä, Päivi, additional, Gursoy, Ulvi, additional, Anttonen, Vuokko, additional, Sipilä, Kirsi, additional, Laivuori, Hannele, additional, Kurra, Venla, additional, Kotaniemi-Talonen, Laura, additional, Heikinheimo, Oskari, additional, Kalliala, Ilkka, additional, Aaltonen, Lauri, additional, Jokimaa, Varpu, additional, Vääräsmäki, Marja, additional, Uimari, Outi, additional, Morin-Papunen, Laure, additional, Niinimäki, Maarit, additional, Piltonen, Terhi, additional, Kivinen, Katja, additional, Widen, Elisabeth, additional, Tukiainen, Taru, additional, Välimäki, Niko, additional, Laakkonen, Eija, additional, Tyrmi, Jaakko, additional, Silven, Heidi, additional, Sliz, Eeva, additional, Arffman, Riikka, additional, Savukoski, Susanna, additional, Laisk, Triin, additional, Pujol, Natalia, additional, Kumar, Janet, additional, Hovatta, Iiris, additional, Isometsä, Erkki, additional, Veerapen, Kumar, additional, Ollila, Hanna, additional, Suvisaari, Jaana, additional, Als, Thomas Damm, additional, Mäkitie, Antti, additional, Bizaki-Vallaskangas, Argyro, additional, Toppila-Salmi, Sanna, additional, Willberg, Tytti, additional, Saarentaus, Elmo, additional, Aarnisalo, Antti, additional, Rahikkala, Elisa, additional, Aittomäki, Kristiina, additional, Åberg, Fredrik, additional, Kurki, Mitja, additional, Havulinna, Aki, additional, Mehtonen, Juha, additional, Palta, Priit, additional, Hassan, Shabbeer, additional, Della Briotta Parolo, Pietro, additional, Zhou, Wei, additional, Maasha, Mutaamba, additional, Lemmelä, Susanna, additional, Rivas, Manuel, additional, Niemi, Mari E., additional, Liu, Aoxing, additional, Lehisto, Arto, additional, Ganna, Andrea, additional, Llorens, Vincent, additional, Heyne, Henrike, additional, Rämö, Joel, additional, Rodosthenous, Rodos, additional, Strausz, Satu, additional, Palotie, Tuula, additional, Palin, Kimmo, additional, Garcia-Tabuenca, Javier, additional, Siirtola, Harri, additional, Kiiskinen, Tuomo, additional, Lee, Jiwoo, additional, Tsuo, Kristin, additional, Kristiansson, Kati, additional, Hyvärinen, Kati, additional, Ritari, Jarmo, additional, Pylkäs, Katri, additional, Karjalainen, Minna, additional, Mantere, Tuomo, additional, Kangasniemi, Eeva, additional, Heikkinen, Sami, additional, Pitkänen, Nina, additional, Lessard, Samuel, additional, Chatelain, Clément, additional, Terho, Perttu, additional, Soini, Sirpa, additional, Punkka, Eero, additional, Siltanen, Sanna, additional, Kuopio, Teijo, additional, Jalanko, Anu, additional, Shen, Huei-Yi, additional, Kajanne, Risto, additional, Aavikko, Mervi, additional, Kanai, Masahiro, additional, Lahtela, L. Elisa, additional, Kaunisto, Mari, additional, Kilpeläinen, Elina, additional, Sipilä, Timo P., additional, Dada, Oluwaseun Alexander, additional, Ghazal, Awaisa, additional, Kytölä, Anastasia, additional, Weldatsadik, Rigbe, additional, Donner, Kati, additional, Loukola, Anu, additional, Laiho, Päivi, additional, Sistonen, Tuuli, additional, Kaiharju, Essi, additional, Laukkanen, Markku, additional, Järvensivu, Elina, additional, Lähteenmäki, Sini, additional, Männikkö, Lotta, additional, Wong, Regis, additional, Toivola, Auli, additional, Brunfeldt, Minna, additional, Mattsson, Hannele, additional, Koskelainen, Sami, additional, Hiekkalinna, Tero, additional, Paajanen, Teemu, additional, Pärn, Kalle, additional, Kals, Mart, additional, Luo, Shuang, additional, Sinha, Vishal, additional, Niemi, Marianna, additional, Gracia-Tabuenca, Javier, additional, Helminen, Mika, additional, Luukkaala, Tiina, additional, Vähätalo, Iida, additional, Pitkänen, Jyrki, additional, Smith, Sarah, additional, and Southerington, Tom, additional

Published
2024
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36. NGS of brush cytology samples improves the detection of high-grade dysplasia and cholangiocarcinoma in patients with primary sclerosing cholangitis: A retrospective and prospective study

Author

Boyd, Sonja, primary, Mustamäki, Taru, additional, Sjöblom, Nelli, additional, Nordin, Arno, additional, Tenca, Andrea, additional, Jokelainen, Kalle, additional, Rantapero, Tommi, additional, Liuksiala, Thomas, additional, Lahtinen, Laura, additional, Kuopio, Teijo, additional, Kytölä, Soili, additional, Mäkisalo, Heikki, additional, Färkkilä, Martti, additional, and Arola, Johanna, additional

Published
2024
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38. Aberrant DNA methylation distorts developmental trajectories in atypical teratoid/rhabdoid tumors

Author

Pekkarinen, Meeri, primary, Nordfors, Kristiina, additional, Uusi-Mäkelä, Joonas, additional, Kytölä, Ville, additional, Hartewig, Anja, additional, Huhtala, Laura, additional, Rauhala, Minna, additional, Urhonen, Henna, additional, Häyrynen, Sergei, additional, Afyounian, Ebrahim, additional, Yli-Harja, Olli, additional, Zhang, Wei, additional, Helen, Pauli, additional, Lohi, Olli, additional, Haapasalo, Hannu, additional, Haapasalo, Joonas, additional, Nykter, Matti, additional, Kesseli, Juha, additional, and Rautajoki, Kirsi J, additional

Published
2024
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39. Impact of Primary Tumor Location on Demographics, Resectability, Outcomes, and Quality of Life in Finnish Metastatic Colorectal Cancer Patients (Subgroup Analysis of the RAXO Study)

Author

Aho, Sonja, primary, Osterlund, Emerik, additional, Ristimäki, Ari, additional, Nieminen, Lasse, additional, Sundström, Jari, additional, Mäkinen, Markus J., additional, Kuopio, Teijo, additional, Kytölä, Soili, additional, Ålgars, Annika, additional, Ristamäki, Raija, additional, Heervä, Eetu, additional, Kallio, Raija, additional, Halonen, Päivi, additional, Soveri, Leena-Maija, additional, Nordin, Arno, additional, Uutela, Aki, additional, Salminen, Tapio, additional, Stedt, Hanna, additional, Lamminmäki, Annamarja, additional, Muhonen, Timo, additional, Kononen, Juha, additional, Glimelius, Bengt, additional, Isoniemi, Helena, additional, Lehto, Juho T., additional, Lehtomäki, Kaisa, additional, and Osterlund, Pia, additional

Published
2024
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40. Recontacting biobank participants to collect lifestyle, behavioural and cognitive information via online questionnaires: lessons from a pilot study within FinnGen

Author

Oskari Heikinheimo, Athena Matakidou, Jaakko Kaprio, Ying Wu, Kai Kaarniranta, Peeter Karihtala, Wei Zhou, Caroline Fox, Sarah Smith, Apinya Lertratanakul, Katri Kaukinen, Johannes Kettunen, Eeva Sliz, Markus Perola, Veikko Salomaa, Hilkka Soininen, Ilkka Kalliala, Mika Kähönen, Hao Chen, Andrey Loboda, Laure Morin-Papunen, Terhi Piltonen, Anders Mälarstig, Jason Miller, Jussi Hernesniemi, Henrike Heyne, Sirkku Peltonen, Daniel Gordin, Masahiro Kanai, Benjamin Challis, Juha Sinisalo, David Rice, Fredrik Åberg, Aarno Palotie, Samuli Ripatti, Oili Kaipiainen-Seppänen, Aki Havulinna, Satu Strausz, Tuomo Kiiskinen, Sanni Ruotsalainen, Jukka Koskela, Tuula Palotie, Mark Daly, Howard Jacob, Heiko Runz, Sally John, Robert Plenge, Mark McCarthy, Julie Hunkapiller, Dawn Waterworth, Petri Virolainen, Terhi Kilpi, Jukka Partanen, Anne Pitkäranta, Veli-Matti Kosma, Outi Tuovila, Raimo Pakkanen, Shameek Biswas, Xinli Hu, Johanna Schleutker, Mikko Arvas, Olli Carpen, Reetta Hinttala, Arto Mannermaa, Valtteri Julkunen, Anne Remes, Reetta Kälviäinen, Mikko Hiltunen, Jukka Peltola, Pentti Tienari, Juha Rinne, Adam Ziemann, Jeffrey Waring, Nizar Smaoui, Anne Lehtonen, Susan Eaton, Sanni Lahdenperä, Natalie Bowers, Edmond Teng, Fanli Xu, David Pulford, Martti Färkkilä, Sampsa Pikkarainen, Airi Jussila, Timo Blomster, Mikko Kiviniemi, Markku Voutilainen, Fedik Rahimov, Joseph Maranville, Tim Lu, Kirsi Kalpala, Melissa Miller, Linda McCarthy, Kari Eklund, Antti Palomäki, Pia Isomäki, Laura Pirilä, Johanna Huhtakangas, Marla Hochfeld, Nan Bing, Jorge Esparza Gordillo, Nina Mars, Tarja Laitinen, Margit Pelkonen, Paula Kauppi, Hannu Kankaanranta, Terttu Harju, Hubert Chen, Teemu Niiranen, Kaj Metsärinne, Marja-Riitta Taskinen, Tiinamaija Tuomi, Jari Laukkanen, Audrey Chu, Jaakko Parkkinen, Heikki Joensuu, Tuomo Meretoja, Lauri Aaltonen, Annika Auranen, Päivi Auvinen, Klaus Elenius, Relja Popovic, Jennifer Schutzman, Heli Lehtonen, Stefan McDonough, Diptee Kulkarni, Terhi Ollila, Hannu Uusitalo, Erich Strauss, Kaisa Tasanen, Laura Huilaja, Katariina Hannula-Jouppi, Teea Salmi, Leena Koulu, David Choy, Anu Jalanko, Risto Kajanne, Mari Kaunisto, Chia-Yen Chen, Robert Yang, Kirsi Auro, Clement Chatelain, Mitja Kurki, Juha Karjalainen, Kimmo Palin, Priit Palta, Susanna Lemmelä, Manuel Rivas, Arto Lehisto, Andrea Ganna, Vincent Llorens, Kati Kristiansson, Kati Hyvärinen, Jarmo Ritari, Katri Pylkäs, Minna Karjalainen, Tuomo Mantere, Eeva Kangasniemi, Sami Heikkinen, Eija Laakkonen, Anu Loukola, Päivi Laiho, Tuuli Sistonen, Essi Kaiharju, Markku Laukkanen, Elina Järvensivu, Sini Lähteenmäki, Lotta Männikkö, Regis Wong, Hannele Mattsson, Kati Donner, Kalle Pärn, Elina Kilpeläinen, Hannele Laivuori, Harri Siirtola, Lila Kallio, Sirpa Soini, Teijo Kuopio, Ioanna Tachmazidou, Katja Kivinen, Pekka Nieminen, Adam Platt, Sanna Toppila-Salmi, Antti Mäkitie, Elmo Saarentaus, Kristiina Aittomäki, Elisabeth Widen, Marja Vääräsmäki, Erkki Isometsä, Jari Lahti, Laura Addis, Taneli Raivio, Mart Kals, Majd Mouded, Hanna Ollila, Vuokko Anttonen, Robert Graham, Amanda Elliott, Ali Abbasi, Bridget Riley-Gills, Dirk Paul, Katherine Klinger, Deepak Raipal, Antti Hakanen, Raisa Serpi, Johanna Mäkelä, Mengzhen Liu, Neha Raghavan, Adriana Huertas-Vazquez, Nicole Renaud, Roosa Kallionpää, John Eicher, Minna Raivio, Juulia Partanen, Riitta Lahesmaa, Glenda Lassi, Joanna Betts, Rajashree Mishra, Felix Vaura, Joel Rämö, Mary Pat Reeve, Johanna Mattson, Sauli Vuoti, Esa Pitkänen, Joni A Turunen, Stephanie Loomis, Pirkko Pussinen, Aino Salminen, Tuula Salo, Ulla Palotie, Maria Siponen, Liisa Suominen, Päivi Mäntylä, Ulvi Gursoy, Kirsi Sipilä, Venla Kurra, Laura Kotaniemi-Talonen, Outi Uimari, Taru Tukiainen, Niko Välimäki, Janet Kumar, Juha Mehtonen, Shabbeer Hassan, Pietro Della Briotta Parolo, Mutaamba Maasha, Javier Garcia-Tabuenca, Jiwoo Lee, Kristin Tsuo, Nina Pitkänen, Eero Punkka, Huei-Yi Shen, Mervi Aavikko, L. Elisa Lahtela, Timo P. Sipilä, Awaisa Ghazal, Sami Koskelainen, Teemu Paajanen, Shuang Luo, Tiina Luukkaala, Iida Vähätalo, Tero Jyrhämä, Marco Hautalahti, Tom Southerington, Jaana Suvisaari, Zhihao Ding, Qingqin S Li, Amy Hart, Rodosthenis S Rodosthenous, Mari E K Niemi, Merja Perala, Perttu Terho, Theresa Knopp, Enni M Makkonen, Paula Nurmi, Pauli Wihuri, Corianna Moffatt, Paolo Martini, Laura Germine, Viola A Makela, Oona A Karhunen, Tero S Hiekkalinna, Alessandro Porello, Anastasia Kytölä, Antti Aarnisalo, Aoxing Liu, Argyro Bizaki-Vallaskangas, Auli Toivola, Debby Ngo, Dermot Reilly, Ekaterina Khramtsova, Elisa Rahikkala, Eric Green, Eveliina Salminen, Fabiana Farias, George Okafo, Heidi Silven, Heli Salminen-Mankonen, Henna Palin, Iiris Hovatta, Jaakko Tyrmi, Jae-Hoon Sul, Jenni Aittokallio, Jyrki Pitkänen, Karen He, Katriina Aalto-Setälä, Maarit Niinimäki, Malla-Maria Linna, Marc Jung, Margaret G. Ehm, Marianna Niemi, Meijian Guan, Mike Mendelson, Minna Brunfeldt, Natalia Pujol, Nathan Lawless, Oluwaseun Alexander Dada, Rigbe Weldatsadik, Riikka Arffman, Rion Pendergrass, Sahar Mozaffari, Samuel Lessard, Sanna Siltanen, Shanmukha Sampath Padmanabhuni, Simonne Longerich, Susanna Savukoski, Thomas Damm Als, Timo Hiltunen, Tomi P. Mäkelä, Triin Laisk, Tytti Willberg, and Varpu Jokimaa

Subjects
Medicine
Abstract

Objectives To recontact biobank participants and collect cognitive, behavioural and lifestyle information via a secure online platform.Design Biobank-based recontacting pilot study.Setting Three Finnish biobanks (Helsinki, Auria, Tampere) recruiting participants from February 2021 to July 2021.Participants All eligible invitees were enrolled in FinnGen by their biobanks (Helsinki, Auria, Tampere), had available genetic data and were >18 years old. Individuals with severe neuropsychiatric disease or cognitive or physical disabilities were excluded. Lastly, 5995 participants were selected based on their polygenic score for cognitive abilities and invited to the study. Among invitees, 1115 had successfully participated and completed the study questionnaire(s).Outcome measures The primary outcome was the participation rate among study invitees. Secondary outcomes included questionnaire completion rate, quality of data collected and comparison of participation rate boosting strategies.Results The overall participation rate was 18.6% among all invitees and 23.1% among individuals aged 18–69. A second reminder letter yielded an additional 9.7% participation rate in those who did not respond to the first invitation. Recontacting participants via an online healthcare portal yielded lower participation than recontacting via physical letter. The completion rate of the questionnaire and cognitive tests was high (92% and 85%, respectively), and measurements were overall reliable among participants. For example, the correlation (r) between self-reported body mass index and that collected by the biobanks was 0.92.Conclusion In summary, this pilot suggests that recontacting FinnGen participants with the goal to collect a wide range of cognitive, behavioural and lifestyle information without additional engagement results in a low participation rate, but with reliable data. We suggest that such information be collected at enrolment, if possible, rather than via post hoc recontacting.

Published
2022
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41. Androgen Receptor Deregulation Drives Bromodomain-Mediated Chromatin Alterations in Prostate Cancer

Author

Urbanucci, Alfonso, Barfeld, Stefan J, Kytölä, Ville, Itkonen, Harri M, Coleman, Ilsa M, Vodák, Daniel, Sjöblom, Liisa, Sheng, Xia, Tolonen, Teemu, Minner, Sarah, Burdelski, Christoph, Kivinummi, Kati K, Kohvakka, Annika, Kregel, Steven, Takhar, Mandeep, Alshalalfa, Mohammed, Davicioni, Elai, Erho, Nicholas, Lloyd, Paul, Karnes, R Jeffrey, Ross, Ashley E, Schaeffer, Edward M, Griend, Donald J Vander, Knapp, Stefan, Corey, Eva, Feng, Felix Y, Nelson, Peter S, Saatcioglu, Fahri, Knudsen, Karen E, Tammela, Teuvo LJ, Sauter, Guido, Schlomm, Thorsten, Nykter, Matti, Visakorpi, Tapio, and Mills, Ian G

Subjects
Biological Sciences, Urologic Diseases, Prostate Cancer, Aging, Genetics, Cancer, 2.1 Biological and endogenous factors, Aetiology, ATPases Associated with Diverse Cellular Activities, Chromatin, Chromatin Assembly and Disassembly, DNA-Binding Proteins, Gene Expression Regulation, Neoplastic, Humans, Male, Neoplasm Proteins, Prostatic Neoplasms, Castration-Resistant, Protein Serine-Threonine Kinases, Receptors, Androgen, Transcription Factors, ATAD2, BRD2, BRD4, BROMO-10, androgen receptor, bromodomain inhibitor, castration-resistant prostate cancer, chromatin, Biochemistry and Cell Biology, Medical Physiology, Biological sciences
Abstract

Global changes in chromatin accessibility may drive cancer progression by reprogramming transcription factor (TF) binding. In addition, histone acetylation readers such as bromodomain-containing protein 4 (BRD4) have been shown to associate with these TFs and contribute to aggressive cancers including prostate cancer (PC). Here, we show that chromatin accessibility defines castration-resistant prostate cancer (CRPC). We show that the deregulation of androgen receptor (AR) expression is a driver of chromatin relaxation and that AR/androgen-regulated bromodomain-containing proteins (BRDs) mediate this effect. We also report that BRDs are overexpressed in CRPCs and that ATAD2 and BRD2 have prognostic value. Finally, we developed gene stratification signature (BROMO-10) for bromodomain response and PC prognostication, to inform current and future trials with drugs targeting these processes. Our findings provide a compelling rational for combination therapy targeting bromodomains in selected patients in which BRD-mediated TF binding is enhanced or modified as cancer progresses.

Published
2017

43. Impact of Primary Tumor Location on Demographics, Resectability, Outcomes, and Quality of Life in Finnish Metastatic Colorectal Cancer Patients (Subgroup Analysis of the RAXO Study)

Author

Aho, Sonja, Österlund, Emerik, Ristimäki, Ari, Nieminen, Lasse, Sundström, Jari, Mäkinen, Markus J., Kuopio, Teijo, Kytölä, Soili, Ålgars, Annika, Ristamäki, Raija, Heervä, Eetu, Kallio, Raija, Halonen, Päivi, Soveri, Leena-Maija, Nordin, Arno, Uutela, Aki, Salminen, Tapio, Stedt, Hanna, Lamminmäki, Annamarja, Muhonen, Timo, Kononen, Juha, Glimelius, Bengt, Isoniemi, Helena, Lehto, Juho T., Lehtomäki, Kaisa, Österlund, Pia, Aho, Sonja, Österlund, Emerik, Ristimäki, Ari, Nieminen, Lasse, Sundström, Jari, Mäkinen, Markus J., Kuopio, Teijo, Kytölä, Soili, Ålgars, Annika, Ristamäki, Raija, Heervä, Eetu, Kallio, Raija, Halonen, Päivi, Soveri, Leena-Maija, Nordin, Arno, Uutela, Aki, Salminen, Tapio, Stedt, Hanna, Lamminmäki, Annamarja, Muhonen, Timo, Kononen, Juha, Glimelius, Bengt, Isoniemi, Helena, Lehto, Juho T., Lehtomäki, Kaisa, and Österlund, Pia

Abstract

Simple Summary The location of the primary tumor in the right colon, left colon, or rectum affects the efficacy of biological drugs used in the treatment of metastatic colorectal cancer, but how? We examined how the primary tumor location affects disease characteristics, treatability, quality of life, and outcome in a real-life study population of 1080 Finnish patients in the RAXO study. The primary tumor location correlates with the location of metastases, the frequency of gene mutations, how often metastases can be operated upon, long-term survival after curative surgery or palliative chemotherapy, and the quality of life during the disease trajectory. The primary tumor location is a helpful surrogate for clinicians working with metastatic colorectal cancer patients in estimating the clinical course of the disease. This study cannot identify the reasons for the associations, i.e., whether it is the primary location per se, the different mutations, or other reasons.Abstract The primary tumor location (PTL) is associated with the phenotype, metastatic sites, mutations, and outcomes of metastatic colorectal cancer (mCRC) patients, but this has mostly been studied according to sidedness (right vs. left sided). We studied right colon vs. left colon vs. rectal PTL in a real-life study population (n = 1080). Health-related quality of life (HRQoL) was assessed multi-cross-sectionally with QLQ-C30, QLQ-CR29, EQ-5D, and 15D. A chi-square, Kaplan-Meier, and Cox regression were used to compare the groups. The PTL was in the right colon in 310 patients (29%), the left colon in 396 patients (37%), and the rectum in 375 patients (35%). The PTL was associated with distinct differences in metastatic sites during the disease trajectory. The resectability, conversion, and resection rates were lowest in the right colon, followed by the rectum, and were highest in the left colon. Overall survival was shortest for right colon compared with left colon or rectal PTL (median 21 vs. 35 vs.

Published
2024
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44. Atypical (non‐V600E) BRAF mutations in metastatic colorectal cancer in population and real‐world cohorts

Author

Österlund, Emerik, Ristimäki, Ari, Mäkinen, Markus J., Kytölä, Soili, Kononen, Juha, Pfeiffer, Per, Soveri, Leena‐Maija, Keinänen, Mauri, Sorbye, Halfdan, Nunes, Luís, Salminen, Tapio, Nieminen, Lasse, Uutela, Aki, Halonen, Päivi, Ålgars, Annika, Sundström, Jari, Kallio, Raija, Ristamäki, Raija, Lamminmäki, Annamarja, Stedt, Hanna, Heervä, Eetu, Kuopio, Teijo, Sjöblom, Tobias, Isoniemi, Helena, Glimelius, Bengt, Osterlund, Pia, Österlund, Emerik, Ristimäki, Ari, Mäkinen, Markus J., Kytölä, Soili, Kononen, Juha, Pfeiffer, Per, Soveri, Leena‐Maija, Keinänen, Mauri, Sorbye, Halfdan, Nunes, Luís, Salminen, Tapio, Nieminen, Lasse, Uutela, Aki, Halonen, Päivi, Ålgars, Annika, Sundström, Jari, Kallio, Raija, Ristamäki, Raija, Lamminmäki, Annamarja, Stedt, Hanna, Heervä, Eetu, Kuopio, Teijo, Sjöblom, Tobias, Isoniemi, Helena, Glimelius, Bengt, and Osterlund, Pia

Abstract

BRAF-V600E mutation (mt) is a strong negative prognostic and predictive biomarker in metastatic colorectal cancer (mCRC). Non-V600Emt, designated atypical BRAFmt (aBRAFmt) are rare, and little is known about their frequency, co-mutations and prognostic and predictive role. These were compared between mutational groups of mCRC patients collected from three Nordic population-based or real-world cohorts. Pathology of aBRAFmt was studied. The study included 1449 mCRC patients with 51 (3%) aBRAFmt, 182 (13%) BRAF-V600Emt, 456 (31%) RAS&BRAF wild-type (wt) and 760 (52%) RASmt tumours. aBRAFmt were seen in 2% of real-world and 4% of population-based cohorts. Twenty-six different aBRAFmt were detected, 11 (22%) class 2 (serrated adenocarcinoma in 2/9 tested), 32 (64%) class 3 (serrated in 15/25) and 4 (8%) unclassified. aBRAFmt patients were predominantly male, had more rectal primaries, less peritoneal metastases, deficient mismatch repair in one (2%), and better survival after metastasectomy (89% 5-year overall survival [OS]-rate) compared with BRAF-V600Emt. aBRAFmt and BRAF-V600Emt had poorer performance status and received fewer treatment lines than RAS&BRAFwt and RASmt. OS among aBRAFmt (median 14.4 months) was longer than for BRAF-V600Emt (11.2 months), but shorter than for RAS&BRAFwt (30.5 months) and RASmt (23.4 months). Addition of bevacizumab trended for better OS for the aBRAFmt. Nine patients with aBRAFmt received cetuximab/panitumumab without response. aBRAFmt represents a distinct subgroup differing from other RAS/BRAF groups, with serrated adenocarcinoma in only half. OS for patients with aBRAFmt tumours was slightly better than for BRAF-V600Emt, but worse than for RASmt and RAS&BRAFwt. aBRAFmt should not be a contraindication for metastasectomy.

Published
2024
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45. Patient-Specific Measurable Residual Disease Markers Predict Outcome in Patients With Myelodysplastic Syndrome and Related Diseases After Hematopoietic Stem-Cell Transplantation

Author

Tobiasson, Magnus, Pandzic, Tatjana, Illman, Johanna, Nilsson, Lars, Weström, Simone, Ejerblad, Elisabeth, Olesen, Gitte, Björklund, Andreas, Olsnes Kittang, Astrid, Werlenius, Olle, Lorentz, Fryderyk, Rasmussen, Bengt, Cammenga, Jörg, Weber, Duruta, Lindholm, Carolin, Wiggh, Joel, Dimitriou, Marios, Moen, Ann Elin, Yip Lundström, Laimei, von Bahr, Lena, Baltzer-Sollander, Karin, Jädersten, Martin, Kytölä, Soili, Walldin, Gunilla, Ljungman, Per, Groenbaek, Kirsten, Mielke, Stephan, Jacobsen, Sten Eirik W., Ebeling, Freja, Cavelier, Lucia, Smidstrup Friis, Lone, Dybedal, Ingunn, Hellström-Lindberg, Eva, Tobiasson, Magnus, Pandzic, Tatjana, Illman, Johanna, Nilsson, Lars, Weström, Simone, Ejerblad, Elisabeth, Olesen, Gitte, Björklund, Andreas, Olsnes Kittang, Astrid, Werlenius, Olle, Lorentz, Fryderyk, Rasmussen, Bengt, Cammenga, Jörg, Weber, Duruta, Lindholm, Carolin, Wiggh, Joel, Dimitriou, Marios, Moen, Ann Elin, Yip Lundström, Laimei, von Bahr, Lena, Baltzer-Sollander, Karin, Jädersten, Martin, Kytölä, Soili, Walldin, Gunilla, Ljungman, Per, Groenbaek, Kirsten, Mielke, Stephan, Jacobsen, Sten Eirik W., Ebeling, Freja, Cavelier, Lucia, Smidstrup Friis, Lone, Dybedal, Ingunn, and Hellström-Lindberg, Eva

Abstract

PURPOSE: Clinical relapse is the major threat for patients with myelodysplastic syndrome (MDS) undergoing hematopoietic stem-cell transplantation (HSCT). Early detection of measurable residual disease (MRD) would enable preemptive treatment and potentially reduced relapse risk. METHODS: Patients with MDS planned for HSCT were enrolled in a prospective, observational study evaluating the association between MRD and clinical outcome. We collected bone marrow (BM) and peripheral blood samples until relapse, death, or end of study 24 months after HSCT. Patient-specific mutations were identified with targeted next-generation sequencing (NGS) panel and traced using droplet digital polymerase chain reaction (ddPCR). RESULTS: Of 266 included patients, estimated relapse-free survival (RFS) and overall survival (OS) rates 3 years after HSCT were 59% and 64%, respectively. MRD results were available for 221 patients. Relapse was preceded by positive BM MRD in 42/44 relapses with complete MRD data, by a median of 71 (23-283) days. Of 137 patients in continuous complete remission, 93 were consistently MRD-negative, 39 reverted from MRD+ to MRD-, and five were MRD+ at last sampling. Estimated 1 year-RFS after first positive MRD was 49%, 39%, and 30%, using cutoff levels of 0.1%, 0.3%, and 0.5%, respectively. In a multivariate Cox model, MRD (hazard ratio [HR], 7.99), WHO subgroup AML (HR, 4.87), TP53 multi-hit (HR, 2.38), NRAS (HR, 3.55), and acute GVHD grade III-IV (HR, 4.13) were associated with shorter RFS. MRD+ was also independently associated with shorter OS (HR, 2.65). In a subgroup analysis of 100 MRD+ patients, presence of chronic GVHD was associated with longer RFS (HR, 0.32). CONCLUSION: Assessment of individualized MRD using NGS + ddPCR is feasible and can be used for early detection of relapse. Positive MRD is associated with shorter RFS and OS (ClinicalTrials.gov identifier: NCT02872662)., Supported by project grants to E.H.-L. from the Knut and Alice Wallenberg Foundation, the Swedish Cancer Society, the Scientific Research Council, the Stockholm Cancer Society, and the Stockholm County Council. M.T. was supported by project grants from the Swedish Society of Medicine, SFO, CIMED, and the Tobias Foundation. The study was also supported by a project grant from the Nordic Cancer Union and by an unrestricted grant from Celgene Inc.

Published
2024
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46. Pure partition functions of multiple SLEs

Author

Kytölä, Kalle and Peltola, Eveliina

Subjects
Mathematical Physics, Mathematics - Analysis of PDEs, Mathematics - Probability, Mathematics - Quantum Algebra, Mathematics - Representation Theory, 60D05, 81T40, 82B27, 16T05, 35C15, 33C70
Abstract

Multiple Schramm-Loewner Evolutions (SLE) are conformally invariant random processes of several curves, whose construction by growth processes relies on partition functions: M\"obius covariant solutions to a system of second order partial differential equations. In this article, we use a quantum group technique to construct a distinguished basis of solutions, which conjecturally correspond to the extremal points of the convex set of probability measures of multiple SLEs., Comment: 47 pages, 15 figures, to appear in Communications in Mathematical Physics

Published
2015
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47. Diagnostic yield of genetic testing in a heterogeneous cohort of 1376 HCM patients

Author

Julie Hathaway, Krista Heliö, Inka Saarinen, Jonna Tallila, Eija H. Seppälä, Sari Tuupanen, Hannu Turpeinen, Tiia Kangas-Kontio, Jennifer Schleit, Johanna Tommiska, Ville Kytölä, Miko Valori, Mikko Muona, Johanna Sistonen, Massimiliano Gentile, Pertteli Salmenperä, Samuel Myllykangas, Jussi Paananen, Tero-Pekka Alastalo, Tiina Heliö, and Juha Koskenvuo

Subjects
Hypertrophic cardiomyopathy, Genetic testing, Next generation sequencing, Diagnosis, Counseling, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Abstract Background Genetic testing in hypertrophic cardiomyopathy (HCM) is a published guideline-based recommendation. The diagnostic yield of genetic testing and corresponding HCM-associated genes have been largely documented by single center studies and carefully selected patient cohorts. Our goal was to evaluate the diagnostic yield of genetic testing in a heterogeneous cohort of patients with a clinical suspicion of HCM, referred for genetic testing from multiple centers around the world. Methods A retrospective review of patients with a suspected clinical diagnosis of HCM referred for genetic testing at Blueprint Genetics was undertaken. The analysis included syndromic, myopathic and metabolic etiologies. Genetic test results and variant classifications were extracted from the database. Variants classified as pathogenic (P) or likely pathogenic (LP) were considered diagnostic. Results A total of 1376 samples were analyzed. Three hundred and sixty-nine tests were diagnostic (26.8%); 373 P or LP variants were identified. Only one copy number variant was identified. The majority of diagnostic variants involved genes encoding the sarcomere (85.0%) followed by 4.3% of diagnostic variants identified in the RASopathy genes. Two percent of diagnostic variants were in genes associated with a cardiomyopathy other than HCM or an inherited arrhythmia. Clinical variables that increased the likelihood of identifying a diagnostic variant included: an earlier age at diagnosis (p

Published
2021
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50. Targeting Apoptosis Pathways With BCL2 and MDM2 Inhibitors in Adult B-cell Acute Lymphoblastic Leukemia

Author

Helena Hohtari, Matti Kankainen, Shady Adnan-Awad, Bhagwan Yadav, Swapnil Potdar, Aleksandr Ianevski, Olli Dufva, Caroline Heckman, Veronika Sexl, Soili Kytölä, Satu Mustjoki, and Kimmo Porkka

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

In adult patients, the treatment outcome of acute lymphoblastic leukemia (ALL) remains suboptimal. Here, we used an ex vivo drug testing platform and comprehensive molecular profiling to discover new drug candidates for B-ALL. We analyzed sensitivity of 18 primary B-ALL adult patient samples to 64 drugs in a physiological concentration range. Whole-transcriptome sequencing and publicly available expression data were used to examine gene expression biomarkers for observed drug responses. Apoptotic modulators targeting BCL2 and MDM2 were highly effective. Philadelphia chromosome–negative (Ph–) samples were sensitive to both BCL2/BCL-W/BCL-XL-targeting agent navitoclax and BCL2-selective venetoclax, whereas Ph-positive (Ph+) samples were more sensitive to navitoclax. Expression of BCL2 was downregulated and BCL-W and BCL-XL upregulated in Ph+ ALL compared with Ph– samples, providing elucidation for the observed difference in drug responses. A majority of the samples were sensitive to MDM2 inhibitor idasanutlin. The regulatory protein MDM2 suppresses the function of tumor suppressor p53, leading to impaired apoptosis. In B-ALL, the expression of MDM2 was increased compared with other hematological malignancies. In B-ALL cell lines, a combination of BCL2 and MDM2 inhibitor was synergistic. In summary, antiapoptotic proteins including BCL2 and MDM2 comprise promising targets for future drug studies in B-ALL.

Published
2022
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