Review
Environmental Sciences
Aurelie Nakamura, Olivier Francois, Johanna Lepeule
Summary: In utero exposure to maternal tobacco smoking can lead to epigenetic changes affecting the birth and development of infants, with DNA methylation being the most extensively studied mechanism. Some studies suggest reversibility in certain genomic regions of DNAm and memory of smoking exposure in other regions, especially in cases of smoking cessation before or during pregnancy.
INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH
(2021)
Article
Environmental Sciences
Nichole Nidey, Katherine Bowers, Lili Ding, Hong Ji, Robert T. Ammerman, Kimberly Yolton, E. Melinda Mahabee-Gittens, Alonzo T. Folger
Summary: This study investigated the effects of in-utero exposure to maternal smoking on DNA methylation of AVPR1a gene in infants. The findings suggest that infants with in-utero exposure to maternal smoking have reduced DNA methylation at AVPR1a CpG sites.
Article
Oncology
Richard Xu, Xiumei Hong, Boyang Zhang, Wanyu Huang, Wenpin Hou, Guoying Wang, Xiaobin Wang, Tak Igusa, Liming Liang, Hongkai Ji
Summary: This study in a predominantly urban, low-income multi-ethnic birth cohort in the US found that maternal smoking significantly affects newborn birthweight, and fetal DNA methylation may play an important mediating role in the impact of maternal smoking on newborn birthweight.
CLINICAL EPIGENETICS
(2021)
Article
Genetics & Heredity
Parnian Kheirkhah Rahimabad, A. Daniel Jones, Hongmei Zhang, Su Chen, Yu Jiang, Susan Ewart, John W. Holloway, Hasan Arshad, Shakiba Eslamimehr, Robert Bruce, Wilfried Karmaus
Summary: This study aimed to investigate whether polymorphisms in GST genes influence the effect of MSP on offspring DNAm. The results showed that in males, GST gene polymorphisms modified the associations between hydroxycotinine and DNAm, as well as between norcotinine and DNAm. In females, GST gene polymorphisms also modified the associations between hydroxycotinine and DNAm, as well as between norcotinine and DNAm. This study highlights the role of genetic polymorphism in GST genes in the susceptibility of DNAm to MSP.
Article
Reproductive Biology
Jordan M. Buck, Li Yu, Valerie S. Knopik, Jerry A. Stitzel
Summary: Maternal smoking during pregnancy can have negative impacts on children's neurodevelopment, while grandmaternal smoking may also lead to neurodevelopmental abnormalities in grandchildren. Research suggests that epigenetic changes, particularly DNA methylome perturbations, play a key role in these abnormalities.
BIOLOGY OF REPRODUCTION
(2021)
Article
Biochemistry & Molecular Biology
E. Antoun, P. Titcombe, K. Dalrymple, N. T. Kitaba, S. J. Barton, Ac Flynn, R. Murray, E. S. Garratt, P. T. Seed, S. L. White, Cyrus Cooper, H. M. Inskip, M. Hanson, L. Poston, K. M. Godfrey, K. A. Lillycrop
Summary: The study identified neonatal methylation changes associated with birthweight and specific maternal factors, suggesting potential insights into developmental pathways affecting birthweight and surrogate markers for adverse prenatal exposures linked to non-communicable diseases.
Article
Genetics & Heredity
Tingting Wang, Pingtian Xia, Ping Su
Summary: Epigenome-wide mediation analysis reveals that DNA methylation plays a mediating role in the association between smoking and Crohn's disease. Changes in methylation at certain sites are associated with an increased risk of Crohn's disease.
FRONTIERS IN GENETICS
(2022)
Review
Allergy
Lisa M. Wheatley, John W. Holloway, Cecilie Svanes, Malcolm R. Sears, Carrie Breton, Alexey V. Fedulov, Eric Nilsson, Donata Vercelli, Hongmei Zhang, Alkis Togias, Syed Hasan Arshad
Summary: There is increasing evidence that environmental exposures can have transgenerational effects on health, even without direct exposure to the original factor. Epigenetic factors may play a role in these cross-generational effects. Animal studies have shown that asthma risk can be transmitted across generations from a single exposure to a harmful factor, partly through changes in DNA methylation. The association between a father's prepuberty exposure and offspring's risk of asthma and lung function deficit may also be mediated by epigenetic processes.
CLINICAL AND EXPERIMENTAL ALLERGY
(2022)
Article
Public, Environmental & Occupational Health
Marta Cosin-Tomas, Ariadna Cilleros-Portet, Sofia Aguilar-Lacasana, Nora Fernandez-Jimenez, Mariona Bustamante
Summary: Studies have shown that maternal smoking during pregnancy leads to changes in offspring's DNA methylation, with effects potentially lasting for years depending on the length and dosage of exposure. DNA methylation scores have been developed as biomarkers to estimate past exposure to maternal smoking during pregnancy.
CURRENT ENVIRONMENTAL HEALTH REPORTS
(2022)
Article
Oncology
Lyndsey E. Shorey-Kendrick, Cindy T. McEvoy, Shannon M. O'Sullivan, Kristin Milner, Brittany Vuylsteke, Robert S. Tepper, David M. Haas, Byung Park, Lina Gao, Annette Vu, Cynthia D. Morris, Eliot R. Spindel
Summary: Maternal smoking during pregnancy impacts multiple organ systems in the fetus and offspring, with lifelong deficits in pulmonary function and increased risk of respiratory issues. Vitamin C supplementation can ameliorate the adverse effects of maternal smoking on placental DNA methylation and gene expression, potentially improving placental function and respiratory health outcomes in offspring. Further research is needed to validate candidate loci and elucidate the causal pathway between placental methylation changes and outcomes in offspring exposed to maternal smoking.
CLINICAL EPIGENETICS
(2021)
Article
Cell Biology
Lei Cao-Lei, Marion I. van den Heuvel, Klaus Huse, Matthias Platzer, Guillaume Elgbeili, Marijke A. K. A. Braeken, Renee A. Otte, Otto W. Witte, Matthias Schwab, Bea R. H. van den Bergh
Summary: Epigenetic changes related to altered behavior and neuropsychiatric disorders are associated with maternal anxiety during pregnancy. The study found a link between maternal anxiety and children's DNA methylation levels, with sex differences and timing effects being highly important. However, DNA methylation was not supported as the underlying mechanism for the impact of maternal anxiety during pregnancy on offspring's behavioral measures.
Article
Multidisciplinary Sciences
Michelle Z. L. Kee, Ai Ling Teh, Andrew Clappison, Irina Pokhvisneva, Julie L. MacIssac, David T. S. Lin, Katia E. Ramadori, Birit F. P. Broekman, Helen Chen, Mary Lourdes Daniel, Neerja Karnani, Michael S. Kobor, Peter D. Gluckman, Yap Seng Chong, Jonathan Y. Huang, Michael J. Meaney
Summary: This study found an association between prenatal maternal depressive symptoms and inter-individual genome-wide DNA methylation, specifically in mothers carrying female fetuses. It also revealed sex-dependent associations with depression-related genes and signaling pathways, suggesting the potential role of maternal-fetal interactions in intergenerational transmission.
Article
Neurosciences
Ulrike Weber-Stadlbauer, Juliet Richetto, Ramona A. J. Zwamborn, Roderick C. Slieker, Urs Meyer
Summary: Prenatal exposure to infectious and/or inflammatory insults is increasingly recognized to contribute to the etiology of psychiatric disorders with neurodevelopmental components. Recent research using animal models suggests that maternal immune activation (MIA) can induce transgenerational effects on brain and behavior, possibly through epigenetic mechanisms. From a mouse model study, it was found that MIA had the potential to modify dopaminergic functions across multiple generations with opposite effects in the direct descendants and their progeny, indicating a potential role of epigenetic processes in the male germline in the transgenerational effects of MIA.
NEUROPSYCHOPHARMACOLOGY
(2021)
Review
Obstetrics & Gynecology
Jagyashila Das, Arindam Maitra
Summary: Multiple factors influence pregnancy, including environmental, behavioral, and hereditary factors. Recent studies indicate that DNAm modifications can impact maternal and fetal health, leading to clinical adversities. Changes in DNAm in promoter and enhancer regions can modulate gene expression and play a vital physiological role.
REPRODUCTIVE SCIENCES
(2021)
Article
Genetics & Heredity
Rui Luo, Hongmei Zhang, Nandini Mukherjee, Wilfried Karmaus, Veeresh Patil, Hasan Arshad, Fawaz Mzayek
Summary: This study aimed to assess the intergenerational effects of grandmaternal smoking during pregnancy on the DNA methylation of grandchildren. The authors found that grandmaternal smoking during pregnancy resulted in differential methylation of 23 CpG sites in grandchildren, with 8 of them associated with changes in expression levels of 13 neighboring genes. Hence, grandmaternal smoking during pregnancy has an independent intergenerational effect on the DNA methylation profile of grandchildren.
Article
Rheumatology
Sarah L. N. Clarke, Ruth E. Mitchell, Gemma C. Sharp, Athimalaipet V. Ramanan, Caroline L. Relton
Summary: Using Mendelian randomization (MR), this study examined the causal relationship between vitamin D levels and juvenile idiopathic arthritis (JIA) incidence. The results showed no evidence of a causal relationship between 25-(OH)D levels and JIA incidence. Therefore, population-level vitamin D supplementation is unlikely to reduce the incidence of JIA.
ARTHRITIS CARE & RESEARCH
(2023)
Article
Public, Environmental & Occupational Health
Nancy Krieger, Jarvis T. Chen, Christian Testa, Ana Diez Roux, Kate Tilling, Sarah Watkins, Andrew J. Simpkin, Matthew Suderman, George Davey Smith, Immaculata De Vivo, Pamela D. Waterman, Caroline Relton
Summary: Motivated by a literature review, this study reports on the treatment of age in studies on social exposures and accelerated aging using epigenetic clocks. Among 50 reviewed articles, the majority used an incorrect method of analysis, while only 42% used correct methods. The study provides simulation and empirical analyses to illustrate the biases introduced by the incorrect method and recommends best practices.
AMERICAN JOURNAL OF EPIDEMIOLOGY
(2023)
Article
Biochemical Research Methods
Ville Karhunen, Ilkka Launonen, Marjo-Riitta Jarvelin, Sylvain Sebert, Mikko J. Sillanpaa
Summary: FiniMOM is a novel Bayesian fine-mapping method that aims to detect independent causal variants from genetic associations. It uses a nonlocal inverse-moment prior to model non-null effects and a beta-binomial prior to control for potential misspecifications in linkage disequilibrium reference.
Article
Immunology
Carly A. Bobak, Maresa Botha, Lesley Workman, Jane E. Hill, Mark P. Nicol, John W. Holloway, Dan J. Stein, Leonardo Martinez, Heather J. Zar
Summary: This study investigated the relationship between gene expression in umbilical cord blood and the risk of developing tuberculosis (TB) infection and disease in early life. Gene expression signatures were identified that were predictive of TB conversion and progression to TB disease in children with early infection. Coexpression network analysis revealed modules associated with neutrophil activation and defense responses to bacteria. These findings provide novel insights into TB pathogenesis and susceptibility.
CLINICAL INFECTIOUS DISEASES
(2023)
Article
Endocrinology & Metabolism
Diana L. Juvinao-Quintero, Gemma C. Sharp, Eleanor C. M. Sanderson, Caroline L. Relton, Hannah R. Elliott
Summary: This study aimed to provide evidence for a causal relationship between DNA methylation (DNAm) and type 2 diabetes. The researchers used bidirectional two-sample Mendelian randomisation (2SMR) to evaluate the causality at 58 CpG sites. The results showed a strong causal effect of DNAm at cg25536676 (DHCR24) on the risk of type 2 diabetes.
Article
Endocrinology & Metabolism
Yuxia Wei, Tom G. Richardson, Yiqiang Zhan, Sofia Carlsson
Summary: Using Mendelian randomisation, this study investigated whether the effects of childhood adiposity on adult-onset diabetes vary across different diabetes subtypes. The results showed that childhood adiposity had significant genetically predicted effects on severe autoimmune diabetes, severe insulin-deficient diabetes, severe insulin-resistant diabetes, and mild obesity-related diabetes, but not on mild age-related diabetes. These findings highlight the importance of preventing childhood obesity.
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
Public, Environmental & Occupational Health
Scott Waterfield, Tom G. Richardson, George Davey Smith, Linda M. O'Keeffe, Joshua A. Bell
Summary: This study found that genetic variants are more strongly associated with adiposity than with lean mass. Sex-specific childhood genetic risk scores have a larger impact on obesity, while the impact of adulthood genetic risk scores is smaller.
INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
(2023)
Article
Public, Environmental & Occupational Health
Stefan Stender, George Davey Smith, Tom G. Richardson
Summary: The study aimed to determine whether genetic risk factors for fatty liver disease (FLD) begin to exert their deleterious effects during childhood, adolescence, and early adulthood. The results showed that genetic risk factors were associated with elevated liver enzymes starting from childhood and their effects amplified with increasing age.
INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
(2023)
Review
Medicine, General & Internal
Cecilie Svanes, John W. W. Holloway, Susanne Krauss-Etschmann
Summary: Emerging research suggests that exposures occurring years before conception are important determinants of the health of future offspring and subsequent generations. There is increasing evidence that respiratory health is influenced by parental exposures that occur long before conception, such as adolescent tobacco smoking and overweight in future fathers. These exposures have been linked to increased asthma and lower lung function in their offspring. Understanding the potential impact of parental exposures on the health of future generations can lead to the development of preventive strategies and break the cycle of health inequalities across generations.
JOURNAL OF INTERNAL MEDICINE
(2023)
Review
Allergy
Merlijn van Breugel, Rudolf S. N. Fehrmann, Marnix Buegel, Faisal I. Rezwan, John W. Holloway, Martijn C. Nawijn, Sara Fontanella, Adnan Custovic, Gerard H. Koppelman
Summary: The field of medicine is increasingly interested in artificial intelligence (AI), which allows for new research questions and analysis of larger and different types of data. However, there are few applications of AI in the field of allergy that go beyond proof of concepts and provide clinical value. This review provides an understanding of AI concepts, discusses limitations and challenges such as data availability and bias, and explores potential directions to overcome them. It also presents case examples of AI applications in allergy, with a focus on diagnosis and subtyping. The review shares guidelines for good AI practice, prospects for field advancement, and initiatives to increase clinical impact, highlighting the potential of AI in deepening our understanding of disease mechanisms and contributing to precision medicine in allergy.
Letter
Allergy
Aniruddha Rathod, Rajesh Melaram, Hongmei Zhang, Hasan Arshad, Susan Ewart, Meredith Ray, Caroline L. Relton, Wilfried Karmaus, John W. Holloway
CLINICAL AND EXPERIMENTAL ALLERGY
(2023)
Article
Multidisciplinary Sciences
Ashley Budu-Aggrey, Anna Kilanowski, Maria K. Sobczyk, Suyash S. Shringarpure, Ruth Mitchell, Kadri Reis, Anu Reigo, Reedik Maegi, Mari Nelis, Nao Tanaka, Ben M. Brumpton, Laurent F. Thomas, Pol Sole-Navais, Christopher Flatley, Antonio Espuela-Ortiz, Esther Herrera-Luis, Jesus V. T. Lominchar, Jette Bork-Jensen, Ingo Marenholz, Aleix Arnau-Soler, Ayoung Jeong, Katherine A. Fawcett, Hansjorg Baurecht, Elke Rodriguez, Alexessander Couto Alves, Ashish Kumar, Patrick M. Sleiman, Xiao Chang, Carolina Medina-Gomez, Chen Hu, Cheng-jian Xu, Cancan Qi, Sarah El-Heis, Philip Titcombe, Elie Antoun, Joao Fadista, Carol A. Wang, Elisabeth Thiering, Baojun Wu, Sara Kress, Dilini M. Kothalawala, Latha Kadalayil, Jiasong Duan, Hongmei Zhang, Sabelo Hadebe, Thomas Hoffmann, Eric Jorgenson, Helene Choquet, Neil Risch, Pal Njolstad, Ole A. Andreassen, Stefan Johansson, Catarina Almqvist, Tong Gong, Vilhelmina Ullemar, Robert Karlsson, Patrik K. E. Magnusson, Agnieszka Szwajda, Esteban G. Burchard, Jacob P. Thyssen, Torben Hansen, Line L. Karhus, Thomas M. Dantoft, Alexander C. S. N. Jeanrenaud, Ahla Ghauri, Andreas Arnold, Georg Homuth, Susanne Lau, Markus M. Noethen, Norbert Huebner, Medea Imboden, Alessia Visconti, Mario Falchi, Veronique Bataille, Pirro Hysi, Natalia Ballardini, Dorret I. Boomsma, Jouke J. Hottenga, Martina Mueller-Nurasyid, Tarunveer S. Ahluwalia, Jakob Stokholm, Bo Chawes, Ann-Marie M. Schoos, Ana Esplugues, Mariona Bustamante, Benjamin Raby, Syed Arshad, Chris German, Tonu Esko, Lili A. Milani, Andres Metspalu, Chikashi Terao, Katrina Abuabara, Mari Loset, Kristian Hveem, Bo Jacobsson, Maria Pino-Yanes, David P. Strachan, Niels Grarup, Allan Linneberg, Young-Ae Lee, Nicole Probst-Hensch, Stephan Weidinger, Marjo-Riitta Jarvelin, Erik Melen, Hakon Hakonarson, Alan D. Irvine, Deborah Jarvis, Tamar Nijsten, Liesbeth Duijts, Judith M. Vonk, Gerard H. Koppelmann, Keith M. Godfrey, Sheila J. Barton, Bjarke Feenstra, Craig E. Pennell, Peter D. Sly, Patrick G. Holt, L. Keoki Williams, Hans Bisgaard, Klaus Bonnelykke, John Curtin, Angela Simpson, Clare Murray, Tamara Schikowski, Supinda Bunyavanich, Scott T. Weiss, John W. Holloway, Josine L. Min, Sara J. Brown, Marie Standl, Lavinia Paternoster
Summary: This study conducted the largest genome-wide association study (GWAS) on atopic dermatitis (AD) to date, identifying 81 replicated AD-associated loci in Europeans and 10 additional loci in a multi-ancestry analysis. The implicated genes are predominantly involved in immune pathways relevant to atopic inflammation and may offer drug repurposing opportunities.
NATURE COMMUNICATIONS
(2023)
Article
Public, Environmental & Occupational Health
Philip C. Haycock, Maria Carolina Borges, Kimberley Burrows, Rozenn N. Lemaitre, Sean Harrison, Stephen Burgess, Xuling Chang, Jason Westra, Nikhil K. Khankari, Kostas K. Tsilidis, Tom Gaunt, Gibran Hemani, Jie Zheng, Therese Truong, Tracy A. O'Mara, Amanda B. Spurdle, Matthew H. Law, Susan L. Slager, Brenda M. Birmann, Fatemeh Saberi Hosnijeh, Daniela Mariosa, Christopher Amos, Rayjean J. Hung, Wei Zheng, Marc J. Gunter, George Davey Smith, Caroline Relton, Richard M. Martin
Summary: A quality control pipeline was developed to identify and correct metadata errors and other analytical issues in Mendelian randomization studies, thereby improving the reliability of the results.
INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
(2023)
Article
Dermatology
Sadia Haider, Raquel Granell, John A. Curtin, John W. Holloway, Sara Fontanella, Syed Hasan Arshad, Clare S. Murray, Paul Cullinan, Stephen Turner, Graham Roberts, Angela Simpson, Adnan Custovic
Summary: This study provides a comprehensive description of the longitudinal pattern of symptoms in eczema through childhood. By using multidimensional variables and clustering analysis, stable clusters with different genetic characteristics were identified. The study also found differences in the association with risk factors and FLG mutations among different clusters.
BRITISH JOURNAL OF DERMATOLOGY
(2023)
