Editorial Material
Oncology
Jack Bowden
Summary: MR-PHeWAS is a powerful new design for discovering causal mechanisms between a disease and its candidate risk factors, with great potential in cancer research when utilizing powerful and principled statistical approaches.
BRITISH JOURNAL OF CANCER
(2021)
Editorial Material
Urology & Nephrology
Michael Turner, Natalie Staplin
Summary: A new Mendelian randomized study discovered that genetically predicted higher levels of urinary uromodulin are linked to lower kidney function and higher blood pressure. Bidirectional and multivariable Mendelian randomization analysis suggested that the association with higher blood pressure may be partially through decreased kidney function, without blood pressure mediating the association of uromodulin with low kidney function.
KIDNEY INTERNATIONAL
(2021)
Article
Genetics & Heredity
Keisuke Ejima, Nianjun Liu, Luis Miguel Mestre, Gustavo de los Campos, David B. Allison
Summary: Mendelian randomization (MR) is often used in epidemiological studies, but it can be biased when confounding variables are correlated with the instrumental variable. In this study, a new approach is proposed to condition on parental mating types in MR, which can reduce bias and the need for assumptions. Simulation results show that this approach eliminates type I error inflation and bias caused by assortative mating or population stratification.
FRONTIERS IN GENETICS
(2023)
Article
Cardiac & Cardiovascular Systems
Jiangming Sun, Pratibha Singh, Annelie Shami, Ewelina Kluza, Mengyu Pan, Djordje Djordjevic, Natasha Barascuk Michaelsen, Cecilia Kennback, Nicole N. van der Wel, Marju Orho-Melander, Jan Nilsson, Ivan Formentini, Karin Conde-Knape, Esther Lutgens, Andreas Edsfeldt, Isabel Goncalves
Summary: This study identifies the specific locations of atherosclerotic plaque ruptures in human carotid arteries and the underlying mechanisms. The proximal and most stenotic regions are found to be vulnerable to plaque rupture. RNA sequencing reveals differentially expressed genes that distinguish these regions, with matrix metallopeptidase 9 being associated with atherosclerosis risk. These findings provide insights for the development of targeted therapies against plaque rupture.
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
(2023)
Article
Medicine, General & Internal
Xiaojing Gu, Meng Dou, Weiming Su, Zheng Jiang, Qingqing Duan, Bei Cao, Yongping Chen
Summary: A study identified novel proteins potentially associated with schizophrenia through a systematic analytical approach. The results suggested the involvement of neuroinflammation in the pathogenesis of schizophrenia, providing insights for future mechanistic studies and potential treatments.
Article
Dentistry, Oral Surgery & Medicine
Sebastian-Edgar Baumeister, Dennis Freuer, Hansjorg Baurecht, Stefan Lars Reckelkamm, Benjamin Ehmke, Birte Holtfreter, Michael Nolde
Summary: Higher educational attainment is associated with a lower risk of periodontitis, and this association is partly mediated by income, smoking, alcohol consumption, and body mass index. Reducing educational disparities in periodontitis risk may involve addressing downstream risk factors such as income, smoking, and obesity.
JOURNAL OF CLINICAL PERIODONTOLOGY
(2022)
Article
Endocrinology & Metabolism
Minghui Liu, Jian Wu, Meng Gao, Yongchao Li, Weiping Xia, Youjie Zhang, Jinbo Chen, Zhiyong Chen, Zewu Zhu, Hequn Chen
Summary: This study provides Mendelian randomization evidence supporting causal associations of many modifiable risk factors with kidney stones. Sedentary lifestyle, obesity, smoking, and type 2 diabetes mellitus are mediating factors in the causal relationship between educational attainment and kidney stones. These modifiable factors should receive more attention to prevent kidney stones.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Clinical Neurology
Hanyu Zhang, Zengyuan Zhou
Summary: This Mendelian randomization study suggests a potential association between genetically predicted COVID-19 and an increased risk of AD, as well as a reduced risk of ALS and MS.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2022)
Article
Oncology
Xiaomeng Zhang, Xue Li, Yazhou He, Philip J. Law, Susan M. Farrington, Harry Campbell, Ian P. M. Tomlinson, Richard S. Houlston, Malcolm G. Dunlop, Maria Timofeeva, Evropi Theodoratou
Summary: The study found that benign colorectal neoplasms share genetic aetiology with CRC, and that CRC genetic predisposition is associated with diverticular disease.
BRITISH JOURNAL OF CANCER
(2022)
Article
Multidisciplinary Sciences
Jiwoo Lee, Sakari Jukarainen, Antti Karvanen, Padraig Dixon, Neil M. Davies, George Davey Smith, Pradeep Natarajan, Andrea Ganna
Summary: Understanding the causal impact of clinical risk factors on healthcare costs is crucial for evaluating healthcare interventions. Using a genetically-informed design, this study found that waist circumference, body mass index, and blood pressure have significant causal impact on healthcare costs. Increased waist circumference is a major contributor to annual total healthcare costs.
NATURE COMMUNICATIONS
(2023)
Article
Obstetrics & Gynecology
Alvaro Hernaez, Robyn E. Wootton, Christian M. Page, Karoline H. Skara, Abigail Fraser, Tormod Rogne, Per Magnus, Pal R. Njolstad, Ole A. Andreassen, Stephen Burgess, Deborah A. Lawlor, Maria Christine Magnus
Summary: Smoking intensity in women is associated with increased infertility odds, while later smoking initiation and smoking cessation are linked to decreased infertility in women. However, the association between greater smoking intensity in men and infertility is not robust.
FERTILITY AND STERILITY
(2022)
Article
Gastroenterology & Hepatology
Antonio F. Di'Narzo, Sander M. Houten, Roman Kosoy, Ruiqi Huang, Frederic M. Vaz, Ruixue Hou, Gabrielle Wei, Wenhui Wang, Phillip H. Comella, Tetyana Dodatko, Eduard Rogatsky, Aleksandar Stojmirovic, Carrie Brodmerkel, Jacqueline Perrigoue, Amy Hart, Mark Curran, Joshua R. Friedman, Jun Zhu, Manasi Agrawal, Judy Cho, Ryan Ungaro, Marla C. Dubinsky, Bruce E. Sands, Mayte Suarez-Farinas, Eric E. Schadt, Jean-Frederic Colombel, Andrew Kasarskis, Ke Hao, Carmen Argmann
Summary: This study used an integrated analysis of genetics and metabolomics to identify metabolites associated with inflammatory bowel disease (IBD) and explored their causal relationships. The findings provide insights into disease activity and potential biomarkers for IBD.
Article
Nutrition & Dietetics
Ho-Sun Lee, Sanghwan In, Taesung Park
Summary: This study utilized Mendelian Randomization to investigate the causal influence of Homocysteine (Hcy) on Metabolic Syndrome (MetS) and found that increased Hcy levels were significantly associated with increased risk of MetS in the Korean population.
Article
Medicine, General & Internal
Maxime M. Bos, Neil J. Goulding, Matthew A. Lee, Amy Hofman, Mariska Bot, Rene Pool, Lisanne S. Vijfhuizen, Xiang Zhang, Chihua Li, Rima Mustafa, Matt J. Neville, Ruifang Li-Gao, Stella Trompet, Marian Beekman, Nienke R. Biermasz, Dorret I. Boomsma, Irene de Boer, Constantinos Christodoulides, Abbas Dehghan, Ko Willems van Dijk, Ian Ford, Mohsen Ghanbari, Bastiaan T. Heijmans, M. Arfan Ikram, J. Wouter Jukema, Dennis O. Mook-Kanamori, Fredrik Karpe, Annemarie I. Luik, L. H. Lumey, Arn M. J. M. van den Maagdenberg, Simon P. Mooijaart, Renee de Mutsert, Brenda W. J. H. Penninx, Patrick C. N. Rensen, Rebecca C. Richmond, Frits R. Rosendaal, Naveed Sattar, Robert A. Schoevers, P. Eline Slagboom, Gisela M. Terwindt, Carisha S. Thesing, Kaitlin H. Wade, Carolien A. Wijsman, Gonneke Willemsen, Aeilko H. Zwinderman, Diana van Heemst, Raymond Noordam, Deborah A. Lawlor
Summary: The study found that insomnia symptoms were associated with lower citrate and higher glycoprotein acetyls, while longer sleep duration was associated with higher creatinine concentrations and isoleucine. These effects may help explain the impact of sleep traits on coronary heart disease and warrant further exploration.
Article
Public, Environmental & Occupational Health
Benjamin Woolf, Nina Di Cara, Christopher Moreno-Stokoe, Veronika Skrivankova, Katie Drax, Julian P. T. Higgins, Gibran Hemani, Marcus R. Munafo, George Davey Smith, James Yarmolinsky, Rebecca C. Richmond
Summary: This study aimed to assess the reporting quality of studies that used MR-Base, one of the most popular platforms for implementing 2SMR analysis. The results showed that the reporting quality was generally poor, with many items needed for evaluating key assumptions being poorly reported. There was no evidence of a difference in reporting quality between studies that used MR-Base and those that did not.
INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
(2022)
Article
Rehabilitation
Karlien Mul, Feri Wijayanto, Tom G. J. Loonen, Perry Groot, Sanne C. C. Vincenten, Simone Knuijt, Jan T. Groothuis, Thomas J. J. Maal, Tom Heskes, Nicol C. Voermans, Baziel G. M. van Engelen
Summary: This study developed a functional assessment measure for evaluating the functional disabilities associated with facial weakness in facioscapulohumeral muscular dystrophy (FSHD). The measure demonstrated good reliability and validity, and can be used as a tool for further research.
DISABILITY AND REHABILITATION
(2023)
Article
Neurosciences
Yongbin Wei, Siemon C. de Lange, Jeanne E. Savage, Elleke Tissink, Ting Qi, Jonathan Repple, Marius Gruber, Tilo Kircher, Udo Dannlowski, Danielle Posthuma, Martijn P. van den Heuvel
Summary: This study examines the impact of genetic susceptibility to schizophrenia and bipolar disorder on brain connectivity. The findings suggest that the genetic liability of SCZ and BD is associated with normative variations in brain circuitry.
BIOLOGICAL PSYCHIATRY
(2023)
Article
Clinical Neurology
Nike Zoe Welander, Gull Rukh, Mathias Rask-Andersen, Aster V. E. Harder, Arn M. J. M. van den Maagdenberg, Helgi Birgir Schioth, Jessica Mwinyi
Summary: This study found no evidence of a shared genetic basis or of a causal association between migraine and either IBD or celiac disease. However, there were indications of causal associations between celiac disease and migraine subtypes. Further research is needed to investigate these associations.
Article
Clinical Neurology
Amir H. Talebi, Jan H. L. Ypinga, Nienke M. De Vries, Jorik Nonnekes, Marten Munneke, Bas R. Bloem, Tom Heskes, Yoav Ben-Shlomo, Sirwan K. L. Darweesh
Summary: Specialized physiotherapy and occupational therapy can reduce the incidence rate of Parkinson's disease-related complications. There may be a synergistic effect among multiple specialized allied health disciplines. The findings of this study support the introduction of specialized allied health therapy expertise in Parkinson's disease care.
MOVEMENT DISORDERS
(2023)
Article
Clinical Neurology
Ka-Hoo Lam, Ioan Gabriel Bucur, Pim Van Oirschot, Frank De Graaf, Eva Strijbis, Bernard Uitdehaag, Tom Heskes, Joep Killestein, Vincent De Groot
Summary: This study investigated the use of remote smartphone-based 2-minute walking tests (s2MWTs) in assessing and detecting changes in ambulatory function in multiple sclerosis (MS) patients. The results showed that s2MWTs had large variability and were not sensitive to changes in clinical outcomes. However, individual-level curve fitting analysis was able to reduce variability and detect statistically reliable changes in ambulatory function in 45% of patients.
MULTIPLE SCLEROSIS JOURNAL
(2023)
Review
Neurosciences
Matthieu C. de Hemptinne, Danielle Posthuma
Summary: Genome-wide association studies have provided valuable insights into brain and behavioral traits, but they also raise ethical concerns regarding privacy and misuse. Better regulation and guidelines are needed to ensure responsible use of genetic data, and researchers should be cautious about the potential negative impacts of their findings.
NATURE NEUROSCIENCE
(2023)
Article
Multidisciplinary Sciences
Douglas P. Wightman, Jeanne E. Savage, Christiaan A. de Leeuw, Iris E. Jansen, Danielle Posthuma
Summary: Proxy phenotypes based on parental diagnosis status have been used to identify common variants associated with Alzheimer's disease, but rare variants have not been investigated. In this study, a proxy phenotype for Alzheimer's disease/dementia was generated for a large population cohort and rare variant aggregation analyses successfully identified genes associated with the proxy phenotype. Three of these genes were replicated in an independent cohort and have been previously linked to clinically diagnosed Alzheimer's disease. This study demonstrates the utility of proxy phenotypes in identifying genes associated with Alzheimer's disease through rare variant aggregation.
SCIENTIFIC REPORTS
(2023)
Editorial Material
Multidisciplinary Sciences
Emil Uffelmann, Danielle Posthuma, Wouter J. Peyrot
SCIENTIFIC REPORTS
(2023)
Article
Psychiatry
Pritesh Jain, Tyne Miller-Fleming, Apostolia R. Topaloudi, Dongmei K. Yu, Petros Drineas, Marianthi Georgitsi, Zhiyu Yang, Renata Rizzo, Kirsten R. Mueller-Vahl, Zeynep A. Tumer, Nanette Mol Debes, Andreas S. Hartmann, Christel E. Depienne, Yulia S. Worbe, Pablo Mir, Danielle C. Cath, Dorret Boomsma, Veit Roessner, Tomasz Wolanczyk, Piotr Janik, Natalia Szejko, Cezary Zekanowski, Csaba Barta, Zsofia Nemoda, Zsanett Tarnok, Joseph D. Buxbaum, Dorothy Grice, Jeffrey Glennon, Hreinn Stefansson, Bastian Hengerer, Noa Benaroya-Milshtein, Francesco Cardona, Tammy Hedderly, Isobel Heyman, Chaim Huyser, Astrid Morer, Norbert Mueller, Alexander Munchau, Kerstin J. Plessen, Cesare Porcelli, Susanne Walitza, Anette Schrag, Davide Martino, Andrea Dietrich, Carol A. Mathews, Jeremiah M. Scharf, Pieter J. Hoekstra, Lea K. Davis, Peristera Paschou
TRANSLATIONAL PSYCHIATRY
(2023)
Article
Clinical Neurology
Max J. J. Oosterwegel, Jesse H. H. Krijthe, Melina G. H. E. den Brok, Lieneke van den Heuvel, Edo Richard, Tom Heskes, Bastiaan R. R. Bloem, Luc J. W. Evers
Summary: This study found no clinically significant effects of cardiovascular risk factors on the clinical progression of Parkinson's disease, based on the analysis of two large cohorts of de novo PD patients.
FRONTIERS IN NEUROLOGY
(2023)
Article
Neurosciences
Elleke Tissink, Josefin Werme, Siemon C. de Lange, Jeanne E. Savage, Yongbin Wei, Christiaan A. de Leeuw, Mats Nagel, Danielle Posthuma, Martijn P. van den Heuvel
Summary: This study explores the genetic component of structural and functional connections within resting-state networks (RSNs) and their potential impact on brain disorders. It identifies genes involved in axon guidance and synaptic functioning in the visual network, and reveals the genetic overlap between RSN-FC alterations and brain disorders.
Article
Biochemistry & Molecular Biology
Daniel S. Malawsky, Eva van Walree, Benjamin M. Jacobs, Teng Hiang Heng, Qin Qin Huang, Ataf H. Sabir, Saadia Rahman, Saghira Malik Sharif, Ahsan Khan, Masa Umicevic Mirkov, Hiroyuki Kuwahara, Xin Gao, Fowzan S. Alkuraya, Danielle Posthuma, William G. Newman, Christopher J. Griffiths, Rohini Mathur, David A. van Heel, Sarah Finer, Jared O'Connell, Hilary C. Martin
Summary: This study investigated the association between autozygosity and common diseases, and discovered an effective method to reduce confounding. The results suggest that autozygosity has significant impact on common diseases, especially for type 2 diabetes among British Pakistanis.
Article
Geriatrics & Gerontology
Douglas P. Wightman, Jeanne E. Savage, Elleke Tissink, Cato Romero, Iris E. Jansen, Danielle Posthuma
Summary: Neurodegenerative diseases are a group of disorders characterized by neuronal cell death, causing various physical and mental problems. This study identified genetic overlap between three or more neurodegenerative disorders, including shared genetic loci, important genes, and tissues. These findings are important for understanding and treating neurodegenerative diseases.
NEUROBIOLOGY OF AGING
(2023)
Article
Neurosciences
Vera Fominykh, Alexey A. Shadrin, Piotr P. Jaholkowski, Shahram Bahrami, Lavinia Athanasiu, Douglas P. Wightman, Emil Uffelmann, Danielle Posthuma, Geir Selbaek, Anders M. Dale, Srdjan Djurovic, Oleksandr Frei, Ole A. Andreassen
Summary: This study found shared genetic loci between Alzheimer's disease (AD) and Multiple Sclerosis (MS), indicating the commonalities and associations between these diseases in terms of genetic susceptibility. These shared loci are involved in inflammation and neurodegeneration, suggesting potential shared pathological mechanisms.
NEUROBIOLOGY OF DISEASE
(2023)
Article
Clinical Neurology
Lei S. Zhao, Wenhui Zhao, Jin Cao, Yiheng Tu
Summary: This study used genetic data and Mendelian randomization (MR) to reveal the causal relationship between migraine and microstructural white matter (WM). Specifically, the study found that the mode of anisotropy (MO) of the left inferior fronto-occipital fasciculus and the orientation dispersion index (OD) of the right posterior thalamic radiation exerted significant causal effects on migraine. Migraine also had a significant causal effect on the OD of the left superior cerebellar peduncle.
JOURNAL OF HEADACHE AND PAIN
(2023)
