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)
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)
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
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
Immunology
Yangke Cai, Xuan Jia, Liyi Xu, Hanwen Chen, Siyuan Xie, Jianting Cai
Summary: This study used Mendelian Randomization analysis to confirm the causal associations between different subtypes of IL-17 and inflammatory bowel disease (IBD). IL-17B, IL-17E, and IL-17RB were found to be significantly associated with an increased risk of ulcerative colitis (UC), while IL-17C and IL-17RC showed causal effects on the increased risk of Crohn's disease (CD).
FRONTIERS IN IMMUNOLOGY
(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
Multidisciplinary Sciences
Fotios Koskeridis, Evangelos Evangelou, Saredo Said, Joseph J. Boyle, Paul Elliott, Abbas Dehghan, Ioanna Tzoulaki
Summary: In this study, the authors investigated the shared genetic determinants of low-grade inflammation and lipometabolism using a multi-trait GWAS approach. They identified many genetic loci associated with C-reactive protein, which are also related to lipid and glucose metabolism, indicating common biological pathways between inflammation and metabolic traits. Additionally, the study revealed novel pleiotropic loci and unexpected discordant effects between shared traits, with implications for clinical outcomes. These findings provide insights into the shared mechanisms underlying inflammation and lipid metabolism, highlighting potential targets for prevention and therapy.
NATURE COMMUNICATIONS
(2022)
Article
Medicine, General & Internal
Liming Zhang, Yuxiang Wang, Li Qiu, Jian Wu
Summary: This study demonstrates the association between psoriasis and cardiovascular diseases, particularly coronary artery disease and myocardial infarction. Using a genetic approach, the researchers established the causal relationship between psoriasis and these cardiovascular diseases.
Article
Biochemistry & Molecular Biology
Esten. H. Leonardsen, Didac Vidal-Pineiro, James. M. Roe, Oleksandr Frei, Alexey. A. Shadrin, Olena Iakunchykova, Ann-Marie G. de Lange, Tobias Kaufmann, Bernd Taschler, Stephen. M. Smith, Ole. A. Andreassen, Thomas Wolfers, Lars. T. Westlye, Yunpeng Wang
Summary: The difference between chronological age and brain age, known as the brain age gap (BAG), is considered an indicator of brain health. In this study, neural networks were used to estimate BAG based on brain scans from 53,542 individuals. Genome-wide association analysis revealed eight genomic regions significantly associated with BAG, implicating neurological, metabolic, and immunological pathways. Causal relationships were found between BAG and Alzheimer's disease and bipolar disorder, but not Parkinson's disease, major depressive disorder, or schizophrenia.
MOLECULAR PSYCHIATRY
(2023)
Article
Medicine, General & Internal
Qian Yang, Maria C. Magnus, Fanny Kilpi, Gillian Santorelli, Ana Goncalves Soares, Jane West, Per Magnus, John Wright, Siri Eldevik Haberg, Eleanor Sanderson, Deborah A. Lawlor, Kate Tilling, Maria Carolina Borges
Summary: Observational studies have shown that maternal sleep duration is associated with adverse pregnancy and perinatal outcomes. However, it is unclear whether there are nonlinear causal effects. This study used Mendelian randomization and multivariable regression to examine the nonlinear effects of sleep duration on various outcomes. The results suggest that shorter and longer sleep duration may increase the risks of stillbirth, perinatal depression, and low offspring birthweight.
Article
Rheumatology
Yi-Lin Dan, Peng Wang, Zhongle Cheng, Qian Wu, Xue-Rong Wang, De-Guang Wang, Hai-Feng Pan
Summary: The study used Mendelian randomization analysis to investigate the causal relationship between circulating adiponectin levels and the risk of SLE, and found no significant association between the two factors. The results suggest that circulating adiponectin levels may not be a causal factor for SLE, and support the absence of a significant relationship between circulating adiponectin levels and the risk of SLE.
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
Clinical Neurology
Zhizhong Zhang, Mengmeng Wang, Dipender Gill, Xinfeng Liu
Summary: This study investigated the association of genetically predicted smoking and alcohol consumption on poststroke outcomes. The results suggest a causal association between smoking and worse functional outcome after ischemic stroke, while alcohol consumption was not associated with functional outcome.
Article
Endocrinology & Metabolism
Io Ieong Chan, Man Ki Kwok, C. Mary Schooling
Summary: This study investigated the association between pubertal maturation timing and adulthood blood pressure using Mendelian randomization (MR) with larger genome-wide association studies (GWAS) data. The results showed a significant correlation between pubertal maturation timing and adulthood blood pressure, independent of childhood body mass index (BMI).
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2022)
Article
Public, Environmental & Occupational Health
Fernando Pires Hartwig, Linbo Wang, George Davey Smith, Neil Martin Davies
Summary: Instrumental variables (IVs) can be used to determine the causal effect of a treatment X on an outcome Y. Further assumptions, such as homogeneity in the causal effect of X on Y and no effect modification, are needed to identify the average causal effect (ACE) of X on Y. The assumption of no simultaneous heterogeneity is sufficient for identifying the ACE using IVs, even if other assumptions are violated.
Article
Public, Environmental & Occupational Health
Ciarrah-Jane S. Barry, Venexia M. Walker, Rosa Cheesman, George Davey Smith, Tim T. Morris, Neil M. Davies
Summary: This article provides an overview of the methods commonly used in genetic epidemiology to estimate heritability. It covers family-based designs, genomic designs based on unrelated individuals, and family-based genomic designs. The article describes the estimation methods and assumptions for each method, and discusses the implications when these assumptions are not met. It also examines the benefits and limitations of estimating heritability within samples of unrelated individuals compared with samples of related individuals.
INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
(2023)
Article
Medicine, General & Internal
Fergus W. Hamilton, Matt J. Thomas, David Arnold, Tom Palmer, Ed Moran, Alexander J. Mentzer, Nick Maskell, Kenneth M. Baillie, Charlotte Summers, Aroon Hingorani, Alasdair MacGowan, Golam M. J. Khandaker, Ruth Mitchell, George Davey Smith, Peter Ghazal, Nicholas J. Timpson
Summary: IL6R blockade is associated with a decreased risk of sepsis and improved survival, similar to its effect in severe COVID-19. Randomized controlled trials of IL-6 receptor antagonists in sepsis should be considered.
Article
Medicine, General & Internal
Si M. Fang, James Yarmolinsky, Dipender R. Gill, Caroline G. Bull, Claire Perks, George Davey Smith, Tom Gaunt, Tom Richardson
Summary: This study used drug target Mendelian randomisation (MR) analysis to evaluate the impact of drug targets associated with low-density lipoprotein cholesterol (LDL-c) lowering therapies on the risk of prostate cancer (PrCa). The findings suggest that genetically proxied inhibition of PCSK9 is associated with a lower risk of total and early-onset PrCa, potentially through the regulation of Lp(a).
Article
Public, Environmental & Occupational Health
Grace Marion Power, Jonathan H. Tobias, Timothy M. Frayling, Jessica Tyrrell, April E. Hartley, Jon E. Heron, George Davey Smith, Tom G. Richardson
Summary: Using a lifecourse Mendelian randomisation approach, this study investigated the influence of body size on fracture risk. The results showed that larger body size in childhood reduces fracture risk, while larger body size in adulthood increases fracture risk.
EUROPEAN JOURNAL OF EPIDEMIOLOGY
(2023)
Article
Public, Environmental & Occupational Health
Tom G. Richardson, Helena Urquijo, Michael Holmes, George Davey Smith
Summary: By applying lifecourse Mendelian randomization to parental history data from the UK Biobank study, we evaluated the direct impact of childhood body size on 8 major disease endpoints. The findings suggest that the increased risk of heart disease and diabetes associated with childhood body size may be attributed to long-term overweight. Furthermore, remaining overweight throughout the lifecourse was found to increase the risk of lung cancer, partly mediated by lifetime smoking index. However, being overweight in childhood may have a protective effect on the risk of breast cancer.
EUROPEAN JOURNAL OF EPIDEMIOLOGY
(2023)
Article
Cardiac & Cardiovascular Systems
Linda M. O'Keeffe, Kate Tilling, Joshua A. Bell, Patrick T. Walsh, Matthew A. Lee, Deborah A. Lawlor, George Davey Smith, Patricia M. Kearney
Summary: This study quantified sex-specific trajectories of 148 metabolic traits from age 7 years to 25 years and found that females had higher VLDL particle concentrations at 7 years but decreased by 25 years, while males showed little change. Additionally, females had lower HDL particle concentrations at 7 years but increased by 25 years, while males showed no significant change.
Article
Multidisciplinary Sciences
Miranda Rogers, Dipender Gill, Emma Ahlqvist, Tim Robinson, Daniela Mariosa, Mattias Johansson, Ricardo Cortez Cardoso Penha, Laure Dossus, Marc J. Gunter, Victor Moreno, George Davey Smith, Richard M. Martin, James Yarmolinsky
Summary: Preclinical and genetic studies show that impaired GIPR signaling increases glycemic control difficulties and its relationship with cancer risk influenced by impaired glucose homeostasis is unclear. This study examines a variant in GIPR, rs1800437 (E354Q), which impairs long-term GIPR signaling, and its association with the risk of 6 cancers influenced by impaired glucose homeostasis. The results suggest that the E354Q variant is associated with higher risk of breast cancer and has adverse effects on glucose concentrations, insulin secretion, and testosterone concentrations.
Article
Peripheral Vascular Disease
Hannah C. M. Taylor, Nishi Chaturvedi, George Davey Smith, Diana L. S. Ferreira, Abigail Fraser, Laura D. Howe, Alun D. Hughes, Debbie A. Lawlor, Nic J. Timpson, Chloe M. Park
Summary: This study investigated the appropriate allometric scaling relationships between left ventricular mass (LVM) and height, total lean mass, and body surface area in healthy adolescents. The results suggest that pooled data without adjustment for sex may introduce bias in allometric scaling estimates. Clinicians should consider body size, body composition, sex, and age when assessing left ventricular mass.
Article
Endocrinology & Metabolism
Kaitlin H. Wade, Fergus W. Hamilton, David Carslake, Naveed Sattar, George Davey Smith, Nicholas J. Timpson
Summary: Mendelian randomization (MR) is a commonly used method for strengthening causal inference by utilizing the properties of genetic variation. Nonlinear MR allows estimation of the shape of such relationships. In this study, the authors explore the utility and biases of these nonlinear MR methods using a negative control design.
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
Cell Biology
Daniel B. Rosoff, Lucas A. Mavromatis, Andrew S. Bell, Josephin Wagner, Jeesun Jung, Riccardo E. Marioni, George Davey Smith, Steve Horvath, Falk W. Lohoff
Summary: By analyzing multiple aging-related phenotypes, this study identified genetic variants and genes associated with aging. Furthermore, it discovered potential drug targets that could improve healthy aging. These findings will contribute to future research on aging and health.
Review
Genetics & Heredity
Sarah Holmes Watkins, Christian Testa, Jarvis T. Chen, Immaculata De Vivo, Andrew J. Simpkin, Kate Tilling, Ana V. Diez Roux, George Davey Smith, Pamela D. Waterman, Matthew Suderman, Caroline Relton, Nancy Krieger
Summary: Epigenetic clocks are used to assess the impact of various phenotypes and exposures on healthy ageing, but little attention has been paid to the sociodemographic characteristics of the participants on whom these clocks are based. This review found that sociodemographic characteristics are generally poorly reported in the construction of commonly used epigenetic clocks. Clear reporting of participant characteristics is important to ensure the appropriateness of the model for other researchers.
ENVIRONMENTAL EPIGENETICS
(2023)
Letter
Endocrinology & Metabolism
George Davey Smith
LANCET DIABETES & ENDOCRINOLOGY
(2023)
Article
Medicine, Research & Experimental
Zhe Wang, George Davey Smith, Ruth J. F. Loos, Marcel den Hoed
Summary: The study investigates the causal relationships between physical activity, sedentary behavior, education, and body mass index (BMI) using genetic information. The results suggest that being more physically active is associated with a lower BMI, while sedentary behavior is a consequence of higher BMI. Additionally, more years of education are linked to higher levels of physical activity, less screen time, and lower BMI. These findings highlight the positive impact of education on health and emphasize the role of physical activity in preventing obesity.
COMMUNICATIONS MEDICINE
(2023)
