Article
Multidisciplinary Sciences
Wei-Yu Lin, Sarah E. Fordham, Nicola Sunter, Claire Elstob, Thahira Rahman, Elaine Willmore, Colin Shepherd, Gordon Strathdee, Tryfonia Mainou-Fowler, Rachel Piddock, Hannah Mearns, Timothy Barrow, Richard S. Houlston, Helen Marr, Jonathan Wallis, Geoffrey Summerfield, Scott Marshall, Andrew Pettitt, Christopher Pepper, Christopher Fegan, Francesco Forconi, Martin J. S. Dyer, Sandrine Jayne, April Sellors, Anna Schuh, Pauline Robbe, David Oscier, James Bailey, Syed Rais, Alison Bentley, Lynn Cawkwell, Paul Evans, Peter Hillmen, Guy Pratt, David J. Allsup, James M. Allan
Summary: Prognostication in CLL patients is challenging due to its heterogeneous clinical course. This study identifies two genomic locations associated with disease progression, highlighting the impact of constitutional genetic variation on CLL prognosis. Additionally, functional genes implicated in modulating key pathways in CLL pathogenesis are identified.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Fasil Tekola-Ayele, Xuehuo Zeng, Suvo Chatterjee, Marion Ouidir, Corina Lesseur, Ke Hao, Jia Chen, Markos Tesfaye, Carmen J. Marsit, Tsegaselassie Workalemahu, Ronald Wapner
Summary: Abnormal birthweight is associated with increased risk for cardiometabolic diseases in later life. This study integrated placental methylation and gene expression data with genetic loci associated with birthweight to identify functional genes involved in fetal growth regulation.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Garan Jones, Katerina Trajanoska, Adam J. Santanasto, Najada Stringa, Chia-Ling Kuo, Janice L. Atkins, Joshua R. Lewis, ThuyVy Duong, Shengjun Hong, Mary L. Biggs, Jian'an Luan, Chloe Sarnowski, Kathryn L. Lunetta, Toshiko Tanaka, Mary K. Wojczynski, Ryan Cvejkus, Maria Nethander, Sahar Ghasemi, Jingyun Yang, M. Carola Zillikens, Stefan Walter, Kamil Sicinski, Erika Kague, Cheryl L. Ackert-Bicknell, Dan E. Arking, B. Gwen Windham, Eric Boerwinkle, Megan L. Grove, Misa Graff, Dominik Spira, Ilja Demuth, Nathalie van der Velde, Lisette C. P. G. M. de Groot, Bruce M. Psaty, Michelle C. Odden, Alison E. Fohner, Claudia Langenberg, Nicholas J. Wareham, Stefania Bandinelli, Natasja M. van Schoor, Martijn Huisman, Qihua Tan, Joseph Zmuda, Dan Mellstrom, Magnus Karlsson, David A. Bennett, Aron S. Buchman, Philip L. De Jager, Andre G. Uitterlinden, Uwe Voelker, Thomas Kocher, Alexander Teumer, Leocadio Rodriguez-Manas, Francisco J. Garcia, Jose A. Carnicero, Pamela Herd, Lars Bertram, Claes Ohlsson, Joanne M. Murabito, David Melzer, George A. Kuchel, Luigi Ferrucci, David Karasik, Fernando Rivadeneira, Douglas P. Kiel, Luke C. Pilling
Summary: Low muscle strength is a heritable indicator of poor health in older people, with genetic loci associated with muscle weakness identified through genome-wide meta-analysis. Possible causal relationships with diabetes susceptibility, hematological parameters, and the immune system were also discovered using Mendelian randomization. The distinct mechanisms of muscle weakness from continuous strength were highlighted, shedding light on potential pathways involved in ageing.
NATURE COMMUNICATIONS
(2021)
Article
Medicine, General & Internal
Lorraine N. Clark, Yizhe Gao, Gao T. Wang, Nora Hernandez, Allison Ashley-Koch, Joseph Jankovic, Ruth Ottman, Suzanne M. Leal, Sandra M. Barral Rodriguez, Elan D. Louis
Summary: This study analyzed whole genome sequence data to identify novel candidate genes and pathways associated with essential tremor. The findings provide new insights into the genetic architecture of the disease and can guide future genetic and functional studies.
Article
Genetics & Heredity
Guimin Gao, Peter N. Fiorica, Julian McClellan, Alvaro N. Barbeira, James L. Li, Olufunmilayo I. Olopade, Hae Kyung Im, Dezheng Huo
Summary: GWAS has identified over 200 genomic loci associated with breast cancer risk, but the specific causal genes in most of these loci have not been identified. Using TWAS and multi-tissue data, we discovered candidate genes associated with breast cancer, including new loci.
AMERICAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Genetics & Heredity
Ammarah Ghaffar, Dale R. Nyholt
Summary: We developed a method named GIDEE to prioritize trait-relevant tissues by combining GWAS summary statistic data with tissue-specific eQTL data. The best-performing GIDEE method ranked the known trait-relevant tissue first multiple times across nine training datasets. Application of the GIDEE approach to test datasets provided important prioritization of tissues relevant to the trait's regulatory architecture.
FRONTIERS IN GENETICS
(2023)
Article
Oncology
Daisuke Nishizawa, Ryozo Morino, Rie Inoue, Seii Ohka, Shinya Kasai, Junko Hasegawa, Yuko Ebata, Kyoko Nakayama, Hiroyuki Sumikura, Masakazu Hayashida, Miyuki Yokota, Kazutaka Ikeda
Summary: This study identified several genetic variations associated with the vulnerability to PONV through a genome-wide association study (GWAS), providing valuable information for predicting the vulnerability to PONV.
Article
Biochemistry & Molecular Biology
Qin Di, Angela Piersanti, Qi Zhang, Cristina Miceli, Hui Li, Xiaoyi Liu
Summary: Soybean oil, which is composed of five fatty acids, including linoleic acid (LA), is known for its poor oxidative stability. In this study, we conducted a genome-wide association study (GWAS) using 510 soybean cultivars collected from China to explore the genetic architecture of LA. We identified 37 genes related to oleic acid content, with one candidate gene, Glyma.04G116500.1 (GmWRI14), consistently detected over three years. Overexpression of GmWRI14 resulted in a significant reduction in LA content in soybean seeds, and RNA-seq analysis confirmed that the downregulation of the FAD2 gene is the underlying mechanism. This study provides novel insights into the genetic control of LA in soybean and identifies potential candidate genes for further investigations.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Plant Sciences
Xing Huo, Jian Wang, Luo Chen, Hua Fu, Tifeng Yang, Jingfang Dong, Yamei Ma, Lian Zhou, Jiansong Chen, Dilin Liu, Bin Liu, Junliang Zhao, Shaohong Zhang, Wu Yang
Summary: Grain chalkiness is a crucial factor influencing the market value of rice. This study identified 34 QTLs associated with grain chalkiness in 450 rice accessions through a genome-wide association analysis. Four candidate genes were identified as potential targets for molecular breeding to improve rice quality. These findings contribute to a better understanding of the genetic basis of grain chalkiness and provide gene resources for quality improvement in rice through molecular breeding.
FRONTIERS IN PLANT SCIENCE
(2023)
Article
Multidisciplinary Sciences
Laura J. Smyth, Emma H. Dahlstrom, Anna Syreeni, Katie Kerr, Jill Kilner, Ross Doyle, Eoin Brennan, Viji Nair, Damian Fermin, Robert G. Nelson, Helen C. Looker, Christopher Wooster, Darrell Andrews, Kerry Anderson, Gareth J. McKay, Joanne B. Cole, Rany M. Salem, Peter J. Conlon, Matthias Kretzler, Joel N. Hirschhorn, Denise Sadlier, Catherine Godson, Jose C. Florez, Carol Forsblom, Alexander P. Maxwell, Per-Henrik Groop, Niina Sandholm, Amy Jayne McKnight
Summary: This study investigated DNA methylation in 1304 individuals with type 1 diabetes and identified differentially methylated CpG sites associated with diabetic kidney disease. The methylation at 21 of these sites was found to predict the development of kidney failure.
NATURE COMMUNICATIONS
(2022)
Article
Plant Sciences
Hui Xia, Ziyuan Hao, Yufang Shen, Zhonghua Tu, Lichun Yang, Yaxian Zong, Huogen Li
Summary: In this study, GWAS analysis identified multiple significant loci associated with growth trajectories in hybrid Liriodendron populations. These loci showed temporal variations in effect sizes and inheritance patterns potentially related to different growth and development stages. The identified loci can be beneficial for selecting superior genotypes and provide a foundation for future molecular-assisted breeding.
Article
Plant Sciences
Rui Wang, Zhenzhen Zhou, Mengyuan Xiong, Mingyu Du, Xingxing Lin, Cuiping Liu, Mingwei Lu, Zhengbo Liu, Yinping Chang, Erbao Liu
Summary: Eight QTLs related to salt tolerance traits were detected, and three candidate genes were predicted, providing a reference for breeding salt-tolerant rice varieties.
Article
Agronomy
Haijiang Liu, Maoyan Zou, Bingbing Zhang, Xinyu Yang, Pan Yuan, Guangda Ding, Fangsen Xu, Lei Shi
Summary: This study conducted a genome-wide association study on the genetic mechanisms of seed yield in oilseed rape, and identified several significant SNPs associated with seed yield. Two candidate genes were identified through transcriptome and candidate gene analysis. These results provide valuable information and resources for understanding the genetic control of seed yield in oilseed rape and breeding high-yield cultivars.
MOLECULAR BREEDING
(2022)
Article
Environmental Sciences
Xinghai Zhu, Junhao Zhang, Xiujiang Hou, Pingping Liu, Jia Lv, Qiang Xing, Xiaoting Huang, Jingjie Hu, Zhenmin Bao
Summary: GWAS analysis revealed the genetic basis of shell color in bay scallops, identifying key SNPs mainly located on chromosome 7 and three candidate genes involved in shell pigmentation regulation. Gene expression analysis showed significant differences in the expression levels of candidate genes in mantle tissues of individuals with different shell colors, providing insights into the mechanism underlying shell color phenotype differences.
FRONTIERS IN MARINE SCIENCE
(2021)
Article
Oncology
Daisuke Nishizawa, Takeshi Terui, Kunihiko Ishitani, Shinya Kasai, Junko Hasegawa, Kyoko Nakayama, Yuko Ebata, Kazutaka Ikeda
Summary: Considerable individual differences in sensitivity to opioids have been observed. In a genome-wide association study of cancer pain patients, specific SNPs were found to be significantly associated with opioid analgesic requirements. These findings may contribute to personalized pain treatment.
Article
Clinical Neurology
Eric Yu, Uladzislau Rudakou, Lynne Krohn, Kheireddin Mufti, Jennifer A. Ruskey, Farnaz Asayesh, Mehrdad A. Estiar, Dan Spiegelman, Matthew Surface, Stanley Fahn, Cheryl H. Waters, Lior Greenbaum, Alberto J. Espay, Yves Dauvilliers, Nicolas Dupre, Guy A. Rouleau, Sharon Hassin-Baer, Edward A. Fon, Roy N. Alcalay, Ziv Gan-Or
Summary: The study found no association between heterozygous single-nucleotide variants and CNVs in PRKN and the risk of PD. Pathogenic and likely-pathogenic variants were less common among PD patients than controls, with no associations found with age at onset.
MOVEMENT DISORDERS
(2021)
Article
Clinical Neurology
Kheireddin Mufti, Uladzislau Rudakou, Eric Yu, Lynne Krohn, Jennifer A. Ruskey, Farnaz Asayesh, Sandra B. Laurent, Dan Spiegelman, Isabelle Arnulf, Michele T. M. Hu, Jacques Y. Montplaisir, Jean-Francois Gagnon, Alex Desautels, Yves Dauvilliers, Gian Luigi Gigli, Mariarosaria Valente, Francesco Janes, Birgit Hoegl, Ambra Stefani, Evi Holzknecht, Karel Sonka, David Kemlink, Wolfgang Oertel, Annette Janzen, Giuseppe Plazzi, Elena Antelmi, Michela Figorilli, Monica Puligheddu, Brit Mollenhauer, Claudia Trenkwalder, Friederike Sixel-Doering, Valerie Cochen De Cock, Christelle Charley Monaca, Anna Heidbreder, Luigi Ferini-Strambi, Femke Dijkstra, Mineke Viaene, Beatriz Abril, Bradley F. Boeve, Ronald B. Postuma, Guy A. Rouleau, Ziv Gan-Or
Summary: The study found no significant role of autosomal dominant and recessive PD or atypical parkinsonism genes in the risk of iRBD. There was no association between rare heterozygous variants in the tested genes and the risk of iRBD. Homozygous and compound heterozygous carriers were not overrepresented in iRBD patients compared to controls.
MOVEMENT DISORDERS
(2021)
Article
Clinical Neurology
Uladzislau Rudakou, Eric Yu, Lynne Krohn, Jennifer A. Ruskey, Farnaz Asayesh, Yves Dauvilliers, Dan Spiegelman, Lior Greenbaum, Stanley Fahn, Cheryl H. Waters, Nicolas Dupre, Guy A. Rouleau, Sharon Hassin-Baer, Edward A. Fon, Roy N. Alcalay, Ziv Gan-Or
Summary: This study conducted a comprehensive analysis of selected genes associated with Parkinson's disease, identifying significant rare and common genetic variants in genes like SYT11, FGF20, and GCH1. Additionally, potential novel associations were discovered in genes like PM20D1, BST1, and GPNMB. Fine mapping of GWAS loci revealed important insights into the genetics of Parkinson's disease.
Article
Clinical Neurology
Kheireddin Mufti, Eric Yu, Uladzislau Rudakou, Lynne Krohn, Jennifer A. Ruskey, Farnaz Asayesh, Sandra B. Laurent, Dan Spiegelman, Isabelle Arnulf, Michele T. M. Hu, Jacques Y. Montplaisir, Jean-Francois Gagnon, Alex Desautels, Yves Dauvilliers, Gian Luigi Gigli, Mariarosaria Valente, Francesco Janes, Andrea Bernardini, Birgit Hogl, Ambra Stefani, Evi Holzknecht, Karel Sonka, David Kemlink, Wolfgang Oertel, Annette Janzen, Giuseppe Plazzi, Elena Antelmi, Michela Figorilli, Monica Puligheddu, Brit Mollenhauer, Claudia Trenkwalder, Friederike Sixel-Doring, Valerie Cochen De Cock, Christelle Charley Monaca, Anna Heidbreder, Luigi Ferini-Strambi, Femke Dijkstra, Mineke Viaene, Beatriz Abril, Bradley F. Boeve, Jean-Francois Trempe, Guy A. Rouleau, Ronald B. Postuma, Ziv Gan-Or
Summary: Rare coding variants in BST1 and rare noncoding variants in LAMP3 are associated with iRBD. Further studies are needed to confirm these findings and explore the potential of targeting BST1 loss of function as a therapeutic approach.
Article
Clinical Neurology
Mehrdad A. Estiar, Eric Yu, Ikhlass Haj Salem, Jay P. Ross, Kheireddin Mufti, Fulya Akcimen, Etienne Leveille, Dan Spiegelman, Jennifer A. Ruskey, Farnaz Asayesh, Alain Dagher, Grace Yoon, Mark Tarnopolsky, Kym M. Boycott, Nicolas Dupre, Patrick A. Dion, Oksana Suchowersky, Jean-Francois Trempe, Guy A. Rouleau, Ziv Gan-Or
Summary: The study found a potential association between SPG7 variants and HSP, with a higher frequency of heterozygous SPG7 variants in HSP patients compared to controls. The results suggest complex inheritance patterns, including dominant and digenic/epistasis forms of inheritance.
MOVEMENT DISORDERS
(2021)
Article
Geriatrics & Gerontology
Yuri L. Sosero, Eric Yu, Lynne Krohn, Uladzislau Rudakou, Kheireddin Mufti, Jennifer A. Ruskey, Farnaz Asayesh, Sandra B. Laurent, Dan Spiegelman, Stanley Fahn, Cheryl Waters, S. Pablo Sardi, Sara Bandres-Ciga, Roy N. Alcalay, Ziv Gan-Or, Konstantin Senkevich
Summary: The study found that the LRRK2 p.M1646T variant is associated with an increased risk of PD and elevated GCase activity in peripheral blood. However, the effect of this variant on PD risk is relatively small.
NEUROBIOLOGY OF AGING
(2021)
Article
Cell Biology
Paul J. Hop, Ramona A. J. Zwamborn, Eilis Hannon, Gemma L. Shireby, Marta F. Nabais, Emma M. Walker, Wouter van Rheenen, Joke J. F. A. van Vugt, Annelot M. Dekker, Henk-Jan Westeneng, Gijs H. P. Tazelaar, Kristel R. van Eijk, Matthieu Moisse, Denis Baird, Ahmad Al Khleifat, Alfredo Iacoangeli, Nicola Ticozzi, Antonia Ratti, Jonathan Cooper-Knock, Karen E. Morrison, Pamela J. Shaw, A. Nazli Basak, Adriano Chio, Andrea Calvo, Cristina Moglia, Antonio Canosa, Maura Brunetti, Maurizio Grassano, Marc Gotkine, Yossef Lerner, Michal Zabari, Patrick Vourc'h, Philippe Corcia, Philippe Couratier, Jesus S. Mora Pardina, Teresa Salas, Patrick Dion, Jay P. Ross, Robert D. Henderson, Susan Mathers, Pamela A. McCombe, Merrilee Needham, Garth Nicholson, Dominic B. Rowe, Roger Pamphlett, Karen A. Mather, Perminder S. Sachdev, Sarah Furlong, Fleur C. Garton, Anjali K. Henders, Tian Lin, Shyuan T. Ngo, Frederik J. Steyn, Leanne Wallace, Kelly L. Williams, Miguel Mitne Neto, Ruben J. Cauchi, Ian P. Blair, Matthew C. Kiernan, Vivian Drory, Monica Povedano, Mamede de Carvalho, Susana Pinto, Markus Weber, Guy A. Rouleau, Vincenzo Silani, John E. Landers, Christopher E. Shaw, Peter M. Andersen, Allan F. McRae, Michael A. van Es, R. Jeroen Pasterkamp, Naomi R. Wray, Russell L. McLaughlin, Orla Hardiman, Kevin P. Kenna, Ellen Tsai, Heiko Runz, Ammar Al-Chalabi, Leonard H. van den Berg, Philip Van Damme, Jonathan Mill, Jan H. Veldink
Summary: This study conducted a blood-based epigenome-wide association study meta-analysis and identified differentially methylated positions (DMPs) and genes associated with ALS. The study also found independent associations between ALS and high-density lipoprotein cholesterol, body mass index, white blood cell proportions, and alcohol intake, with cholesterol biosynthesis potentially causally related to ALS. Additionally, DNA methylation at several DMPs and blood cell proportion estimates were associated with survival rate in patients.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Clinical Neurology
Vincent Roy, Jay P. Ross, Remy Pepin, Sergio Cortez Ghio, Alyssa Brodeur, Lydia Touzel Deschenes, Gaetan Le-Bel, Daniel E. Phillips, Genevieve Milot, Patrick A. Dion, Sylvain Guerin, Lucie Germain, Francois Berthod, Francois A. Auger, Guy A. Rouleau, Nicolas Dupre, Francois Gros-Louis
Summary: This study reveals that RNF213 may play a crucial role in maintaining cerebral endothelial cell integrity, and its disruption may contribute to the early pathological mechanism of Moyamoya disease. Additionally, the study further emphasizes the importance of blood-brain barrier integrity.
Article
Clinical Neurology
Calwing Liao, Charles-Etienne Castonguay, Karl Heilbron, Veikko Vuokila, Miranda Medeiros, Gabrielle Houle, Fulya Akcimen, Jay P. Ross, Helene Catoire, Monica Diez-Fairen, Jooeun Kang, Stefanie H. Mueller, Simon L. Girard, Franziska Hopfner, Delia Lorenz, Lorraine N. Clark, Alexandra I. Soto-Beasley, Stephan Klebe, Mark Hallett, Zbigniew K. Wszolek, Manuela Pendziwiat, Oswaldo Lorenzo-Betancor, Klaus Seppi, Daniela Berg, Carles Vilarino-Guell, Ronald B. Postuma, Genevieve Bernard, Nicolas Dupre, Joseph Jankovic, Claudia M. Testa, Owen A. Ross, Thomas Arzberger, Sylvain Chouinard, Elan D. Louis, Paola Mandich, Carmine Vitale, Paolo Barone, Elena Garcia-Martin, Hortensia Alonso-Navarro, Jose A. G. Agundez, Felix Javier Jimenez-Jimenez, Pau Pastor, Alex Rajput, Gunther Deuschl, Gregor Kuhlenbaumer, Inge A. Meijer, Patrick A. Dion, Guy A. Rouleau
Summary: This genome-wide association study identified five independent loci associated with essential tremor (ET), explaining approximately 18% of its heritability. Functional analysis revealed enrichment in cerebellar regions. Genetic correlation analysis showed overlap with Parkinson disease and depression, suggesting common genetic factors.
Article
Biology
Calwing Liao, Veikko Vuokila, Helene Catoire, Fulya Akcimen, Jay P. Ross, Cynthia V. Bourassa, Patrick A. Dion, Inge A. Meijer, Guy A. Rouleau
Summary: This study explores the biology of Tourette's Syndrome (TS) through transcriptome-wide association study and splicing analysis. It reveals increased expression of FLT3 gene in TS and its association with immune-related pathways.
COMMUNICATIONS BIOLOGY
(2022)
Editorial Material
Biochemistry & Molecular Biology
Kristiana Salmon, Jay P. Ross, Vanessa Bertone, Maria Gobbo, Nancy Anoja, Jason Karamchandani, Patrick A. Dion, Guy A. Rouleau, Angela Genge
EUROPEAN JOURNAL OF HUMAN GENETICS
(2022)
Article
Genetics & Heredity
Charles-Etienne Castonguay, Calwing Liao, Anouar Khayachi, Yumin Liu, Miranda Medeiros, Gabrielle Houle, Jay P. Ross, Patrick A. Dion, Guy A. Rouleau
Summary: This study used gene expression analysis to investigate the mechanisms of action of propranolol and primidone in treating essential tremor (ET). The results suggest that these drugs may reduce tremor symptoms by regulating specific genes and pathways, and identify relevant genetic biomarkers for drug responsiveness in ET.
NPJ GENOMIC MEDICINE
(2022)
Article
Genetics & Heredity
Jay P. Ross, Fulya Akcimen, Calwing Liao, Dan Spiegelman, Ben Weisburd, Nicolas Dupre, Patrick A. Dion, Guy A. Rouleau, Sali M. K. Farhan
Summary: Our study attempted to replicate the association between the CA repeat in the STMN2 gene and the risk for ALS. However, we did not find any evidence supporting this association in our case-control cohort and in genomes from different populations.
NEUROLOGY-GENETICS
(2022)
Article
Genetics & Heredity
Yoshitaka Tamaki, Jay P. Ross, Paria Alipour, Charles-etienne Castonguay, Boting Li, Helene Catoire, Daniel Rochefort, Makoto Urushitani, Ryosuke Takahashi, Joshua A. Sonnen, Stefano Stifani, Patrick A. Dion, Guy A. Rouleau
Summary: This study validated the propagation of TAR DNA-binding protein 43 kDa (TDP-43) pathology in human central nervous system (CNS) using induced pluripotent stem cells (iPSCs)-derived cerebral organoids. The results demonstrated that pathogenic TDP-43 from sporadic ALS patients could induce the formation of TDP-43 pathology in cerebral organoids and spread in a time-dependent manner. Additionally, the administration of ALS patient-derived protein extracts caused astrocyte proliferation, reproducing the pathological feature seen in ALS. These findings highlight the potential of using human cerebral organoids as a promising strategy for ALS research and drug discovery.