Article
Genetics & Heredity
Siqian Chen, Shuli Liu, Siyuan Mi, Wenlong Li, Shengli Zhang, Xiangdong Ding, Ying Yu
Summary: The study utilized whole-genome bisulfite sequencing to analyze sperm DNA methylation levels in three commercial pig breeds, finding varying correlations between breeds and breed-specific hypomethylated regions. Integrating public data revealed high similarity in DNA methylation patterns between human and pig sperm, with conserved regions involved in organ development and brain-related traits. These findings provide insights into male fertility mechanisms and the changes in commercial traits undergoing strong selection.
FRONTIERS IN GENETICS
(2021)
Article
Gastroenterology & Hepatology
Lok-Sze Wong, Lai Wei, Gengchao Wang, Cheuk-Ting Law, Felice Ho-Ching Tsang, Wai-Ching Chin, Irene Oi-Lin Ng, Chun-Ming Wong
Summary: This study comprehensively investigated the functionality of long noncoding RNAs (lncRNAs) in hepatocellular carcinoma (HCC) progression through in vivo functional screening. The study identified positively selected lncRNAs that correlated with aggressive tumor behaviors in HCC patients. The research also revealed the functional roles of the lncRNA candidate CASC11 in cell proliferation and tumor growth, providing insights into the molecular mechanisms of HCC progression.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2022)
Article
Plant Sciences
Jessica Delfini, Vania Moda-Cirino, Jose dos Santos Neto, Douglas Mariani Zeffa, Alison Fernando Nogueira, Luriam Aparecida Brandao Ribeiro, Paulo Mauricio Ruas, Paul Gepts, Leandro Simoes Azeredo Goncalves
Summary: This research aimed to identify Quantitative Trait Nucleotides (QTNs) associated with common bean productivity by evaluating ten morpho-agronomic traits in 178 Mesoamerican common bean domesticated accessions. They identified 64 stable QTNs detected by multiple methods or in multiple environments, with 39 showing significant phenotypic differences between their alleles. The accumulation of favorable alleles resulted in reduced plant height and increased nodules, seed weight, yield, pod insertion height, and number of pods per plant.
FRONTIERS IN PLANT SCIENCE
(2021)
Article
Psychiatry
Hannah M. Heseding, Kirsten Jahn, Christian K. Eberlein, Jelte Wieting, Hannah B. Maier, Phileas J. Proskynitopoulos, Alexander Glahn, Stefan Bleich, Helge Frieling, Maximilian Deest
Summary: This study investigated the methylation rates of the oxytocin receptor gene in individuals with Prader-Willi syndrome (PWS) and found significantly lower methylation levels, particularly in the presence of psychosis. The study also identified E2F1 as a potential transcription factor involved in the regulation of the oxytocin system.
TRANSLATIONAL PSYCHIATRY
(2022)
Article
Genetics & Heredity
Jingjing Li, Jinyan Xu, Tingting Yang, Jianhai Chen, Fuping Li, Bairong Shen, Chuanzhu Fan
Summary: This study revealed a significant alteration in DNA methylation patterns in asthenozoospermic individuals, with many regions located within or adjacent to sperm-related genes. These findings suggest potential methylation markers and epigenetic regulation mechanisms through DNA methylation in asthenozoospermia.
Article
Biology
Vahid Akbari, Jean-Michel Garant, Kieran O'Neill, Pawan Pandoh, Richard Moore, Marco A. Marra, Martin Hirst, Steven J. M. Jones
Summary: This study used nanopore sequencing data to map the imprinted intervals in the human genome. It successfully phased the human methylome and detected both known and novel imprinted DMRs. The study also found several conserved imprinted DMRs in mouse, rhesus monkey, and chimpanzee. These findings expand our understanding of imprinting and demonstrate the potential of nanopore sequencing in identifying imprinting regions.
Article
Biochemistry & Molecular Biology
Lavi S. Bigman, Junji Iwahara, Yaakov Levy
Summary: Intrinsically disordered regions (IDRs) of proteins have a high fraction of charged residues, but their overall net charge and organization differ. This study analyzed the charge properties of IDRs in human, mouse, and yeast proteomes to explore the sequence-function relationship. Negatively charged IDRs were found to be longer and have a higher net charge per residue compared to positively charged IDRs. D/E repeats were longer and more prevalent than K/R repeats, especially in nucleic acid-related proteins.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Huwenbo Shi, Steven Gazal, Masahiro Kanai, Evan M. Koch, Armin P. Schoech, Katherine M. Siewert, Samuel S. Kim, Yang Luo, Tiffany Amariuta, Hailiang Huang, Yukinori Okada, Soumya Raychaudhuri, Shamil R. Sunyaev, Alkes L. Price
Summary: The study identifies that trans-ethnic genetic correlation is significantly less than 1 for many diseases, limiting trans-ethnic polygenic risk prediction. Causal effect sizes are found to be more population-specific in functionally important regions, with skin and immune genes showing the highest population-specificity.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Naisi Zhao, Mengyuan Ruan, Devin C. Koestler, Jiayun Lu, Carmen J. Marsit, Karl T. Kelsey, Elizabeth A. Platz, Dominique S. Michaud
Summary: This study investigated the association between blood DNA methylation levels and lung cancer risk, identifying novel genomic regions and single CpG sites significantly associated with lung cancer risk. These findings serve as potential biomarkers for lung cancer risk stratification and may indicate causal relationships with lung cancer.
Article
Cell & Tissue Engineering
Ece Somuncular, Julia Hauenstein, Prajakta Khalkar, Anne-Sofie Johansson, Ozge Dumral, Nicolai S. Frengen, Charlotte Gustafsson, Giuseppe Mocci, Tsu-Yi Su, Hugo Brouwer, Christine L. Trautmann, Michael Vanlandewijck, Stuart H. Orkin, Robert Mansson, Sidinh Luc
Summary: This study reveals the heterogeneity of hematopoietic stem cells (HSCs) and provides insights into the functional differences and regulatory mechanisms of HSCs through transcriptional and epigenetic mechanisms.
Article
Genetics & Heredity
Jun Wang, Yanqin Niu, Ming Yang, Lirong Shu, Hongxian Wang, Xiaoqian Wu, Yaqin He, Peng Chen, Guocheng Zhong, Zhixiong Tang, Shasha Zhang, Qianwen Guo, Yun Wang, Li Yu, Deming Gou
Summary: This study identified enriched short cfDNA fragments in patients with breast cancer, which were found to originate from hypomethylated genomic regions. Furthermore, the feasibility of using differentially methylated regions (DMRs)-dependent cfDNA fragmentation profile for breast cancer diagnosis was demonstrated.
EPIGENETICS & CHROMATIN
(2023)
Article
Medicine, Research & Experimental
Zijian Chen, Zenghong Huang, Yanxin Luo, Qi Zou, Liangliang Bai, Guannan Tang, Xiaolin Wang, Guangwen Cao, Meijin Huang, Jun Xiang, Huichuan Yu
Summary: This study found that the NTRK3 gene promoter was more frequently methylated in CRC, leading to suppressed gene expression. It was confirmed that NTRK3 promoter methylation was associated with survival outcome in CRC and a nomogram predicting survival outcome was developed. Moreover, NTRK3 promoter methylation also predicted survival outcomes in other tumors.
JOURNAL OF TRANSLATIONAL MEDICINE
(2021)
Article
Genetics & Heredity
Cyril Esnault, Talha Magat, Amal Zine El Aabidine, Encar Garcia-Oliver, Anne Cucchiarini, Soumya Bouchouika, David Lleres, Lutz Goerke, Yu Luo, Daniela Verga, Laurent Lacroix, Robert Feil, Salvatore Spicuglia, Jean-Louis Mergny, Jean-Christophe Andrau
Summary: G4access is a nuclease-based method for identifying DNA G-quadruplex forming regions genome-wide in open chromatin using sequencing. It enriches for computationally predicted G-quadruplexes and allows measurement of variations in G-quadruplex repertoire usage following treatment or inhibition. The study highlights the association of G-quadruplexes with open chromatin, transcription, and DNA methylation, and provides a new tool for studying G4s in cellular dynamics.
Article
Multidisciplinary Sciences
Wei-Yu Lin, Sarah E. Fordham, Eric Hungate, Nicola J. Sunter, Claire Elstob, Yaobo Xu, Catherine Park, Anne Quante, Konstantin Strauch, Christian Gieger, Andrew Skol, Thahira Rahman, Lara Sucheston-Campbell, Junke Wang, Theresa Hahn, Alyssa I. Clay-Gilmour, Gail L. Jones, Helen J. Marr, Graham H. Jackson, Tobias Menne, Mathew Collin, Adam Ivey, Robert K. Hills, Alan K. Burnett, Nigel H. Russell, Jude Fitzgibbon, Richard A. Larson, Michelle M. Le Beau, Wendy Stock, Olaf Heidenreich, Abrar Alharbi, David J. Allsup, Richard S. Houlston, Jean Norden, Anne M. Dickinson, Elisabeth Douglas, Clare Lendrem, Ann K. Daly, Louise Palm, Kim Piechocki, Sally Jeffries, Martin Bornhauser, Christoph Rollig, Heidi Altmann, Leo Ruhnke, Desiree Kunadt, Lisa Wagenfuhr, Heather J. Cordell, Rebecca Darlay, Mette K. Andersen, Maria C. Fontana, Giovanni Martinelli, Giovani Marconi, Miguel A. Sanz, Jose Cervera, Ines Gomez-Segui, Thomas Cluzeau, Chimene Moreilhon, Sophie Raynaud, Heinz Sill, Maria Teresa Voso, Francesco Lo-Coco, Herve Dombret, Meyling Cheok, Claude Preudhomme, Rosemary E. Gale, David Linch, Julia Gaal-Wesinger, Andras Masszi, Daniel Nowak, Wolf-Karsten Hofmann, Amanda Gilkes, Kimmo Porkka, Jelena D. Milosevic Feenstra, Robert Kralovics, David Grimwade, Manja Meggendorfer, Torsten Haferlach, Szilvia Krizsan, Csaba Bodor, Friedrich Stolzel, Kenan Onel, James M. Allan
Summary: The study conducted a genome-wide association analysis on European patients with AML, identifying genetic loci associated with the risk of developing the disease. The results shed light on potential functional genes involved in histone methylation and immune function in AML etiology.
NATURE COMMUNICATIONS
(2021)
Article
Biochemical Research Methods
Chong Wu, Jonathan Bradley, Yanming Li, Lang Wu, Hong-Wen Deng
Summary: The study developed a novel gene-level association testing method that integrates genetically regulated DNA methylation and enhancer-target gene pairs; through simulations, it showed well controlled type I error rates and achieved higher statistical power than competing methods; the CMO method identified more novel genetic loci for AD compared to existing TWAS methods when analyzing GWAS results.
Article
Critical Care Medicine
Shuang A. Guo, Georgina S. Bowyer, John R. Ferdinand, Mailis Maes, Zewen K. Tuong, Eleanor Gillman, Mingfeng Liao, Rik G. H. Lindeboom, Masahiro Yoshida, Kaylee Worlock, Hudaa Gopee, Emily Stephenson, Catherine A. Gao, Paul A. Lyons, Kenneth G. C. Smith, Muzlifah Haniffa, Kerstin B. Meyer, Marko Z. Nikolic, Zheng Zhang, Richard G. Wunderink, Alexander Misharin, Gordon Dougan, Vilas Navapurkar, Sarah A. Teichmann, Andrew Conway Morris, Menna R. Clatworthy
Summary: Obesity has a negative impact on respiratory tract immunity in both adult and pediatric COVID-19 patients, leading to suppressed immune cell responses. Obese individuals show decreased expression of interferon and tumor necrosis factor in lung epithelial and immune cells. These findings have important implications for treatment strategies and recommend the specific application of recombinant interferons in obese patients.
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Qingqin S. Li, Andrey A. Shabalin, Emily DiBlasi, Srihari Gopal, Carla M. Canuso, Aarno Palotie, Wayne C. Drevets, Anna R. Docherty, Hilary Coon
Summary: This study aimed to identify genetic risk variants associated with suicide death and suicidal behavior. The results showed that a locus in the neuroligin 1 (NLGN1) gene was associated with suicide death, while ROBO2 and ZNF28 genes were associated with suicidal behavior. Additionally, variants near SOX5 and LOC101928519 were found to be associated with suicidal attempts. Suicide death and suicidal behavior showed positive correlations with depression, schizophrenia, pain, and suicidal attempt, and negative correlation with educational attainment.
MOLECULAR PSYCHIATRY
(2023)
Article
Multidisciplinary Sciences
Mitja Kurki, Juha Karjalainen, Priit Palta, Timo P. Sipila, Kati Kristiansson, Kati M. Donner, Mary P. Reeve, Hannele Laivuori, Mervi Aavikko, Mari A. Kaunisto, Anu Loukola, Elisa Lahtela, Hannele Mattsson, Paivi Laiho, Pietro Della Briotta Parolo, Arto A. Lehisto, Masahiro Kanai, Nina Mars, Joel Ramo, Tuomo Kiiskinen, Henrike O. Heyne, Kumar Veerapen, Sina Rueger, Susanna Lemmela, Wei Zhou, Sanni Ruotsalainen, Kalle Parn, Tero Hiekkalinna, Sami Koskelainen, Teemu Paajanen, Vincent Llorens, Javier Gracia-Tabuenca, Harri Siirtola, Kadri Reis, Abdelrahman G. Elnahas, Benjamin Sun, Christopher N. Foley, Katriina Aalto-Setala, Kaur Alasoo, Mikko Arvas, Kirsi Auro, Shameek Biswas, Argyro Bizaki-Vallaskangas, Olli Carpen, Chia-Yen Chen, Oluwaseun A. Dada, Zhihao Ding, Margaret G. Ehm, Kari Eklund, Martti Farkkila, Hilary Finucane, Andrea Ganna, Awaisa Ghazal, Robert R. Graham, Eric M. Green, Antti Hakanen, Marco Hautalahti, Asa K. Hedman, Mikko Hiltunen, Reetta Hinttala, Iiris Hovatta, Xinli Hu, Adriana Huertas-Vazquez, Laura Huilaja, Julie Hunkapiller, Howard Jacob, Jan-Nygaard Jensen, Heikki Joensuu, Sally John, Valtteri Julkunen, Marc Jung, Juhani Junttila, Kai Kaarniranta, Mika Kahonen, Risto Kajanne, Lila Kallio, Reetta Kalviainen, Jaakko Kaprio, Nurlan Kerimov, Johannes Kettunen, Elina Kilpelainen, Terhi Kilpi, Katherine Klinger, Veli-Matti Kosma, Teijo Kuopio, Venla Kurra, Triin Laisk, Jari Laukkanen, Nathan Lawless, Aoxing Liu, Simonne Longerich, Reedik Magi, Johanna Makela, Antti Makitie, Anders Malarstig, Arto Mannermaa, Joseph Maranville, Athena Matakidou, Tuomo Meretoja, Sahar Mozaffari, Mari E. K. Niemi, Marianna Niemi, Teemu Niiranen, George Okafo, Hanna M. Ollila, Antti Palomaki, Tuula Palotie, Jukka Partanen, Dirk S. Paul, Margit Pelkonen, Rion K. Pendergrass, Slave Petrovski, Anne Pitkaranta, Adam Platt, David Pulford, Eero Punkka, Pirkko Pussinen, Neha Raghavan, Fedik Rahimov, Deepak Rajpal, Nicole A. Renaud, Bridget Riley-Gillis, Rodosthenis Rodosthenous, Elmo Saarentaus, Aino Salminen, Eveliina Salminen, Veikko Salomaa, Johanna Schleutker, Raisa Serpi, Huei-yi Shen, Richard Siegel, Kaisa Silander, Sanna Siltanen, Sirpa Soini, Hilkka Soininen, Jae Hoon Sul, Ioanna Tachmazidou, Kaisa Tasanen, Pentti Tienari, Sanna Toppila-Salmi, Taru Tukiainen, Tiinamaija Tuomi, Joni A. Turunen, Jacob C. Ulirsch, Felix Vaura, Petri Virolainen, Jeffrey Waring, Dawn Waterworth, Robert Yang, Mari Nelis, Anu Reigo, Andres Metspalu, Lili Milani, Tonu Esko, Caroline Fox, Aki S. Havulinna, Markus Perola, Samuli Ripatti, Anu Jalanko, Tarja Laitinen, Tomi P. Makela, Robert Plenge, Mark McCarthy, Heiko Runz, Mark J. Daly, Aarno Palotie
Summary: Population isolates, like those in Finland, provide valuable insights for genetic research due to the concentration of deleterious alleles in low-frequency variants. FinnGen aims to study the genome and health data of 500,000 Finnish individuals, enabling the identification of new associations and the exploration of their implications for common diseases. The study identified 30 new associations and 2,733 genome-wide significant associations, highlighting the power of bottlenecked populations in uncovering disease biology.
Article
Immunology
Helene Ruffieux, Aimee L. Hanson, Samantha Lodge, Nathan G. Lawler, Luke Whiley, Nicola Gray, Tui H. Nolan, Laura Bergamaschi, Federica Mescia, Lorinda Turner, Aloka de Sa, Victoria S. Pelly, Prasanti Kotagiri, Nathalie R. Kingston, John Bradley, Elaine Holmes, Julien K. Wist, Jeremy A. Nicholson, Paul Lyons, Kenneth G. C. Smith, Sylvia Richardson, Glenn Bantug, Christoph Hess
Summary: We analyzed detailed longitudinal phenotyping data from 215 individuals with varying disease severities to understand the biology behind individual patient responses to SARS-CoV-2 infection. Our findings revealed distinct profiles of 'systemic recovery', including the progression and resolution of inflammatory, immune cell, metabolic, and clinical responses. We identified strong correlations between innate immune cell numbers, kynurenine metabolites, and lipid metabolites, which have implications for homeostasis restoration, risk of death, and long COVID.
Article
Biochemistry & Molecular Biology
Tuomo Kiiskinen, Pyry Helkkula, Kristi Krebs, Juha Karjalainen, Elmo Saarentaus, Nina Mars, Arto Lehisto, Wei Zhou, Mattia Cordioli, Sakari Jukarainen, Joel T. Ramo, Juha Mehtonen, Kumar Veerapen, Markus Rasanen, Sanni Ruotsalainen, Mutaamba Maasha, Teemu Niiranen, Tiinamaija Tuomi, Veikko Salomaa, Mitja Kurki, Matti Pirinen, Aarno Palotie, Mark Daly, Andrea Ganna, Aki S. Havulinna, Lili Milani, Samuli Ripatti
Summary: A new analysis of large biobanks reveals genetic variants associated with changes in medication for cardiometabolic diseases and presents polygenic scores of medication-use behavior. The study used data from the Finnish nationwide drug purchase registry and performed genome-wide association analyses to identify loci associated with medication use in hyperlipidemia, hypertension, and type 2 diabetes. The findings demonstrate the potential for medication-based strategies to identify cardiometabolic risk loci and provide genome-wide tools for preventing cardiovascular diseases.
Article
Multidisciplinary Sciences
Amelie Bonaud, Laetitia Gargowitsch, Simon M. Gilbert, Elanchezhian Rajan, Pablo Canales-Herrerias, Daniel Stockholm, Nabila F. Rahman, Mark O. Collins, Hakan Taskiran, Danika L. Hill, Andres Alloatti, Nagham Alouche, Stephanie Balor, Vanessa Soldan, Daniel Gillet, Julien Barbier, Francoise Bachelerie, Kenneth G. C. Smith, Julia Jellusova, Pierre Bruhns, Sebastian Amigorena, Karl Balabanian, Michelle A. Linterman, Andrew A. Peden, Marion Espeli
Summary: We identified SNARE Sec22b as a critical regulator of plasma cell maintenance and function. In the absence of Sec22b, plasma cells were hardly detectable and serum antibody titers were dramatically reduced, leading to a failure in mounting a protective immune response. Mechanistically, Sec22b contributes to efficient antibody secretion and is involved in regulating plasma cell transcriptional identity, as well as the morphology of the endoplasmic reticulum and mitochondria.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Multidisciplinary Sciences
Eeva Sliz, Jaakko S. Tyrmi, Nilufer Rahmioglu, Krina T. Zondervan, Christian M. Becker, Outi Uimari, Johannes Kettunen, Aarno Palotie, Mark Daly, Bridget Riley-Gills, Howard Jacob, Dirk Paul, Athena Matakidou, Adam Platt, Heiko Runz, Sally John, George Okafo, Nathan Lawless, Heli Salminen-Mankonen, Robert Plenge, Joseph Maranville, Mark McCarthy, Margaret G. Ehm, Kirsi Auro, Simonne Longerich, Caroline Fox, Anders Malarstig, Katherine Klinger, Clement Chatelain, Matthias Gossel, Karol Estrada, Robert Graham, Robert Yang, Chris O'Donnell, Tomi P. Makela, Jaakko Kaprio, Petri Virolainen, Antti Hakanen, Terhi Kilpi, Markus Perola, Jukka Partanen, Anne Pitkaranta, Taneli Raivio, Raisa Serpi, Tarja Laitinen, Veli-Matti Kosma, Jari Laukkanen, Marco Hautalahti, Outi Tuovila, Raimo Pakkanen, Jeffrey Waring, Bridget Riley-Gillis, Fedik Rahimov, Ioanna Tachmazidou, Chia-Yen Chen, Zhihao Ding, Marc Jung, Shameek Biswas, Rion Pendergrass, David Pulford, Neha Raghavan, Adriana Huertas-Vazquez, Jae-Hoon Sul, Xinli Hu, Asa Hedman, Manuel Rivas, Dawn Waterworth, Nicole Renaud, Ma'en Obeidat, Samuli Ripatti, Johanna Schleutker, Mikko Arvas, Olli Carpen, Reetta Hinttala, Arto Mannermaa, Katriina Aalto-Setala, Mika Kahonen, Johanna Makela, Reetta Kalviainen, Valtteri Julkunen, Hilkka Soininen, Anne Remes, Mikko Hiltunen, Jukka Peltola, Minna Raivio, Pentti Tienari, Juha Rinne, Roosa Kallionpaa, Juulia Partanen, Ali Abbasi, Adam Ziemann, Nizar Smaoui, Anne Lehtonen, Susan Eaton, Sanni Lahdenpera, Natalie Bowers, Edmond Teng, Fanli Xu, Laura Addis, John Eicher, Qingqin S. Li, Karen He, Ekaterina Khramtsova, Martti Farkkila, Jukka Koskela, Sampsa Pikkarainen, Airi Jussila, Katri Kaukinen, Timo Blomster, Mikko Kiviniemi, Markku Voutilainen, Tim Lu, Linda McCarthy, Amy Hart, Meijian Guan, Jason Miller, Kirsi Kalpala, Melissa Miller, Kari Eklund, Antti Palomaki, Pia Isomaki, Laura Pirila, Oili Kaipiainen-Seppanen, Johanna Huhtakangas, Nina Mars, Apinya Lertratanakul, Marla Hochfeld, Jorge Esparza Gordillo, Fabiana Farias, Nan Bing, Margit Pelkonen, Paula Kauppi, Hannu Kankaanranta, Terttu Harju, Riitta Lahesmaa, Glenda Lassi, Hubert Chen, Joanna Betts, Rajashree Mishra, Majd Mouded, Debby Ngo, Teemu Niiranen, Felix Vaura, Veikko Salomaa, Kaj Metsarinne, Jenni Aittokallio, Jussi Hernesniemi, Daniel Gordin, Juha Sinisalo, Marja-Riitta Taskinen, Tiinamaija Tuomi, Timo Hiltunen, Amanda Elliott, Mary Pat Reeve, Sanni Ruotsalainen, Benjamin Challis, Audrey Chu, Dermot Reilly, Mike Mendelson, Jaakko Parkkinen, Tuomo Meretoja, Heikki Joensuu, Johanna Mattson, Eveliina Salminen, Annika Auranen, Peeter Karihtala, Paivi Auvinen, Klaus Elenius, Esa Pitkanen, Relja Popovic, Jennifer Schutzman, Diptee Kulkarni, Alessandro Porello, Andrey Loboda, Heli Lehtonen, Stefan McDonough, Sauli Vuoti, Kai Kaarniranta, Joni A. Turunen, Terhi Ollila, Hannu Uusitalo, Juha Karjalainen, Mengzhen Liu, Stephanie Loomis, Erich Strauss, Hao Chen, Kaisa Tasanen, Laura Huilaja, Katariina Hannula-Jouppi, Teea Salmi, Sirkku Peltonen, Leena Koulu, David Choy, Ying Wu, Pirkko Pussinen, Aino Salminen, Tuula Salo, David Rice, Pekka Nieminen, Ulla Palotie, Maria Siponen, Liisa Suominen, Paivi Mantyla, Ulvi Gursoy, Vuokko Anttonen, Kirsi Sipila, Hannele Laivuori, Venla Kurra, Laura Kotaniemi-Talonen, Oskari Heikinheimo, Ilkka Kalliala, Lauri Aaltonen, Varpu Jokimaa, Marja Vaarasmaki, Laure Morin-Papunen, Maarit Niinimaki, Terhi Piltonen, Katja Kivinen, Elisabeth Widen, Taru Tukiainen, Niko Valimaki, Eija Laakkonen, Heidi Silven, Riikka Arffman, Susanna Savukoski, Triin Laisk, Natalia Pujol, Janet Kumar, Iiris Hovatta, Erkki Isometsa, Hanna Ollila, Jaana Suvisaari, Thomas Damm Als, Antti Makitie, Argyro Bizaki-Vallaskangas, Sanna Toppila-Salmi, Tytti Willberg, Elmo Saarentaus, Antti Aarnisalo, Elisa Rahikkala, Kristiina Aittomaki, Fredrik Aberg, Mitja Kurki, Aki Havulinna, Juha Mehtonen, Priit Palta, Shabbeer Hassan, Pietro Della Briotta Parolo, Wei Zhou, Mutaamba Maasha, Susanna Lemmela, Aoxing Liu, Arto Lehisto, Andrea Ganna, Vincent Llorens, Henrike Heyne, Joel Ramo, Rodos Rodosthenous, Satu Strausz, Tuula Palotie, Kimmo Palin, Javier Garcia-Tabuenca, Harri Siirtola, Tuomo Kiiskinen, Jiwoo Lee, Kristin Tsuo, Kati Kristiansson, Kati Hyvarinen, Jarmo Ritari, Katri Pylkas, Minna Karjalainen, Tuomo Mantere, Eeva Kangasniemi, Sami Heikkinen, Nina Pitkanen, Samuel Lessard, Clement Chatelain, Perttu Terho, Tiina Wahlfors, Eero Punkka, Sanna Siltanen, Teijo Kuopio, Anu Jalanko, Huei-Yi Shen, Risto Kajanne, Mervi Aavikko, Henna Palin, Malla-Maria Linna, Masahiro Kanai, Zhili Zheng, L. Elisa Lahtela, Mari Kaunisto, Elina Kilpelainen, Timo P. Sipila, Oluwaseun Alexander Dada, Awaisa Ghazal, Anastasia Kytola, Rigbe Weldatsadik, Kati Donner, Anu Loukola, Paivi Laiho, Tuuli Sistonen, Essi Kaiharju, Markku Laukkanen, Elina Jarvensivu, Sini Lahteenmaki, Lotta Mannikko, Regis Wong, Auli Toivola, Minna Brunfeldt, Hannele Mattsson, Sami Koskelainen, Tero Hiekkalinna, Teemu Paajanen, Kalle Parn, Mart Kals, Shuang Luo, Shanmukha Sampath Padmanabhuni, Marianna Niemi, Javier Gracia-Tabuenca, Mika Helminen, Tiina Luukkaala, Iida Vahatalo, Jyrki Tammerluoto, Sarah Smith, Tom Southerington, Petri Lehto
Summary: Uterine leiomyomata (UL) are the most common tumours in women and often result in surgical removal of the uterus. This study identified 22 new genetic loci associated with UL risk, in addition to the previously known 50 loci. The identified genes are involved in development, growth, and cellular senescence, particularly in the smooth muscle cell differentiation and proliferation pathways.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Joel Raemoe, Tuomo Kiiskinen, Richard Seist, Kristi Krebs, Masahiro Kanai, Juha Karjalainen, Mitja Kurki, Eija Haemaelaeinen, Paavo S. Haeppoelae, Aki Havulinna, Heidi Hautakangas, Reedik Maegi, Priit Palta, Tonu Esko, Andres Metspalu, Matti J. Pirinen, Konrad Karczewski, Samuli Ripatti, Lili M. Milani, Konstantina Stankovic, Antti J. Maekitie, Mark Daly, Aarno Palotie
Summary: Otosclerosis is a common form of hearing loss, with an unclear genetic etiology. A genome-wide association study meta-analysis of otosclerosis identified 27 genetic loci, pointing to genes involved in bone remodeling, skeletal disorders, and transforming growth factor beta signaling.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Elmo Saarentaus, Juha T. Karjalainen, Joel Raemoe, Tuomo S. Kiiskinen, Aki Havulinna, Juha Mehtonen, Heidi Hautakangas, Sanni Ruotsalainen, Max Tamlander, Nina Mars, Sanna Toppila-Salmi, Matti Pirinen, Mitja Kurki, Samuli Ripatti, Mark Daly, Tuula Palotie, Antti Makitie, Aarno Palotie
Summary: In this study, researchers analyzed the genomic similarity of upper respiratory diseases and found 41 genetic loci associated with these diseases, including some linked to immune-related diseases. They also discovered a genetic correlation between upper respiratory diseases and autoimmune conditions such as rheumatoid arthritis and autoimmune hypothyroidism. Moreover, the study revealed shared genetics for type 2 immunological reaction in upper respiratory diseases.
NATURE COMMUNICATIONS
(2023)
Article
Allergy
Dylan Lawless, Hana Lango Allen, James E. D. Thaventhiran, Sarah Goddard, Oliver S. Burren, Evie Robson, N. I. H. R. BioResource Rare Dis Consortium NIHR BioResource Rare Dis Consortium, Daniel Peckham, Kenneth G. C. Smith, Sinisa Savic
Summary: This study analyzed the manifestation of cystic fibrosis (CF), a common genetic disorder, in patients with primary immunodeficiency (PID). The research found that patients carrying specific CFTR gene variants had worse outcome in terms of structural lung disease. Genome sequencing also identified cases of CFTR dysfunction in PID, suggesting the potential of precision medicine in treating traditional Mendelian disorders.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2023)
Article
Ophthalmology
Joel T. Ramo, Erik Abner, Elon H. C. van Dijk, Xin Wang, Joost Brinks, Tiit Nikopensius, Margit Noukas, Heidi Marjonen, Kaisa Silander, Sakari Jukarainen, Tuomo Kiiskinen, Seung Hoan Choi, Risto Kajanne, Juha Mehtonen, Priit Palta, Steven A. Lubitz, Kai Kaarniranta, Lucia Sobrin, Mitja Kurki, Suzanne Yzer, Patrick T. Ellinor, Tonu Esko, Mark J. Daly, Anneke I. den Hollander, Aarno Palotie, Joni A. Turunen, Camiel J. F. Boon, Elizabeth J. Rossin
Summary: This study identified 5 genetic risk loci associated with CSC, indicating the likely involvement of genes related to choroidal vascular function and complement regulation in the pathogenesis of CSC.
JAMA OPHTHALMOLOGY
(2023)
Article
Neurosciences
Antti Tallgren, Leo Kager, Gina O'Grady, Hannu Tuominen, Jarmo Korkko, Outi Kuismin, Martha Feucht, Callum Wilson, Jana Behunova, Eleina England, Mitja I. Kurki, Aarno Palotie, Mikko Hallman, Riitta Kaarteenaho, Franco Laccone, Kaan Boztug, Reetta Hinttala, Johanna Uusimaa
Summary: FINCA disease is an infantile-onset neurodevelopmental and multiorgan disease caused by recessive variants in the NHLRC2 gene. The study reviewed clinical histories of five novel FINCA patients and found that they all presented with neurodevelopmental delay, recurrent infections, and macrocytic anemia. Autopsy samples showed lower intensity of NHLRC2 expression in the brain.
FRONTIERS IN NEUROSCIENCE
(2023)
Letter
Genetics & Heredity
Nina Mars, Joni V. Lindbohm, Pietro della Briotta Parolo, Elisabeth Widen, Jaakko Kaprio, Aarno Palotie, Samuli Ripatti
AMERICAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Cell Biology
Ying Wang, Shinichi Namba, Esteban Lopera, Sini Kerminen, Kristin Tsuo, Kristi Lall, Masahiro Kanai, Wei Zhou, Kuan-Han Wu, Marie-Julie Fave, Laxmi Bhatta, Philip Awadalla, Ben Brumpton, Patrick Deelen, Kristian Hveem, Valeria Lo Faro, Reedik Magi, Yoshinori Murakami, Serena Sanna, Jordan W. Smoller, Jasmina Uzunovic, Cristen Willer, Eric R. Gamazon, Nancy J. Cox, Ida Surakka, Yukinori Okada, Alicia R. Martin, Jibril Hirbo
Summary: This study utilized data from GBMI to explore methodological considerations and performance of PRS for 14 disease endpoints across global populations. The study provides lessons for PRS construction, evaluation, and interpretation and highlights the importance of PRS in the biobank-scale genomics era.