Article
Biochemistry & Molecular Biology
Ciarrah-Jane Shannon Barry, Deborah A. Lawlor, Chin Yang Shapland, Eleanor Sanderson, Maria Carolina Borges
Summary: This study investigated the effects of 46 maternal metabolic traits on offspring birthweight using Mendelian randomisation and metabolomics data. The findings suggest that maternal gestational glucose and glutamine are causally related to offspring birthweight.
Article
Mathematical & Computational Biology
Apostolos Gkatzionis, Stephen Burgess, David Conti, Paul J. Newcombe
Summary: Mendelian randomization is a method that uses genetic variants to assess causal relationships, requiring genetic variants strongly associated with the risk factor and only the outcome through their effects. A novel variable selection algorithm has been developed for this method. In a real-data application, systolic and diastolic blood pressure are shown to have significant risk-increasing effects on coronary heart disease risk.
STATISTICS IN MEDICINE
(2021)
Article
Medicine, General & Internal
Jian Zhao, Isobel D. Stewart, Denis Baird, Dan Mason, John Wright, Jie Zheng, Tom R. Gaunt, David M. Evans, Rachel M. Freathy, Claudia Langenberg, Nicole M. Warrington, Deborah A. Lawlor, Maria Carolina Borges
Summary: This study used two-sample Mendelian randomisation to explore the effect of maternal circulating amino acids on fetal growth. The results indicate that increased levels of maternal glutamine and serine are associated with higher birthweight, while increased levels of leucine and phenylalanine are associated with lower birthweight.
Review
Biochemistry & Molecular Biology
Frederick J. Boehm, Xiang Zhou
Summary: Genome-wide association studies have provided numerous associations for common diseases and complex traits. Mendelian randomization methods, utilizing SNP associations, help uncover causal relationships between complex traits. The availability of GWAS summary statistics has motivated the development of new Mendelian randomization methods with relaxed causality assumptions, offering opportunities for robust biological discoveries.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2022)
Article
Endocrinology & Metabolism
Dong Liu, Yuexin Gan, Yue Zhang, Linlin Cui, Tao Tao, Jun Zhang, Jian Zhao
Summary: Previous studies have reported an association between lower birth weight and higher risk of polycystic ovary syndrome (PCOS), but the causal relationship is still unclear. This study conducted a Mendelian randomization analysis using a large-scale genome-wide association study to investigate the potential causal relationship between fetal genome predicted birth weight and PCOS risk. The results showed little evidence to support a causal effect of fetal genome determined birth weight on the risk of developing PCOS.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Oncology
Richard Culliford, Alex J. Cornish, Philip J. Law, Susan M. Farrington, Kimmo Palin, Mark A. Jenkins, Graham Casey, Michael Hoffmeister, Hermann Brenner, Jenny Chang-Claude, Iva Kirac, Tim Maughan, Stefanie Brezina, Andrea Gsur, Jeremy P. Cheadle, Lauri A. Aaltonen, Malcom G. Dunlop, Richard S. Houlston
Summary: The study did not find a causal relationship between circulating levels of bilirubin or gallstone disease with the risk of developing CRC. The results exclude large effects suggested by observational studies, but cannot rule out the possibility of smaller effects and non-linear relationships.
BRITISH JOURNAL OF CANCER
(2021)
Article
Medicine, General & Internal
Shuai Yuan, Lili Yu, Wanglong Gou, Lijuan Wang, Jing Sun, Doudou Li, Ying Lu, Xiaxia Cai, Huanling Yu, Changzheng Yuan, Ju-Sheng Zheng, Susanna C. Larsson, Evropi Theodoratou, Xue Li
Summary: This study utilized phenome-wide Mendelian randomisation (MR-PheWAS) analysis and systematic review of MR studies to investigate the health effects of serum calcium. The findings suggest that high serum calcium is associated with increased or decreased risk of various diseases, with some associations being replicated in two-sample MR analysis.
Article
Cardiac & Cardiovascular Systems
Nhu Ngoc Le, Tran Quoc Bao Tran, Clea du Toit, Dipender Gill, Sandosh Padmanabhan
Summary: Immune checkpoint inhibitors (ICIs) and Janus kinase inhibitors (JAKis) have raised concerns over serious unexpected cardiovascular adverse events. This study aims to identify cardiovascular risks associated with these drugs and explore potential mechanisms using the Mendelian randomization (MR) approach.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2023)
Article
Medicine, General & Internal
Sonja N. Tang, Verena Zuber, Konstantinos K. Tsilidis
Summary: This study used Mendelian randomisation analysis to investigate the causal relationships between biochemical biomarkers in the UK Biobank and breast cancer. The results suggest that genetically predicted levels of testosterone, HDL cholesterol, and IGF-1 may play a causal role in breast cancer development, and a potential novel role of alkaline phosphatase in breast cancer etiology was discovered.
Article
Medicine, General & Internal
Yiwen Long, Lanhua Tang, Yangying Zhou, Shushan Zhao, Hong Zhu
Summary: This study suggests a causal association between the gut microbiota and cancer, providing new insights for further research on the mechanisms and clinical implications of microbiota-mediated cancer.
Article
Genetics & Heredity
Xue-Lun Zou, Sai Wang, Lei-Yun Wang, Lin-Xiao Xiao, Tian-Xing Yao, Yi Zeng, Le Zhang
Summary: The study found that childhood obesity is significantly associated with an increased risk of stroke, particularly ischemic stroke and large artery stroke. The results remained significant after various sensitivity tests, indicating the robustness of the findings.
FRONTIERS IN GENETICS
(2021)
Review
Physiology
Travis T. Mallard, Andrew D. Grotzinger, Jordan W. Smoller
Summary: Genome-wide association studies have led to reproducible discoveries in psychiatric genetics, identifying hundreds of common genetic variants associated with mental disorders. These findings have the potential to inform the development of new therapeutics, stratify at-risk patients, and possibly revise classification systems in psychiatry. The review summarizes GWAS findings at three levels of analysis: genome-wide architecture, networks and pathways, and individual variants/genes. Three themes emerge: heritability and polygenic nature of psychiatric phenotypes, the importance of neuronal biology and early neurodevelopment, and the involvement of synaptic structure and function in psychopathology. The implications of GWAS results for psychiatry and future directions are also discussed.
PHYSIOLOGICAL REVIEWS
(2023)
Article
Biology
Thomas H. Julian, Johnathan Cooper-Knock, Stuart MacGregor, Hui Guo, Tariq Aslam, Eleanor Sanderson, Graeme C. M. Black, Panagiotis Sergouniotis, Lois E. H. Smith
Summary: Age-related macular degeneration (AMD) is a leading cause of blindness, and this study aims to identify causal factors and potential therapeutic targets for AMD through a phenome-wide Mendelian randomisation (MR) study. The results of this study support several putative causal factors for AMD and provide avenues for future translational research.
Article
Medicine, General & Internal
Ronghuai Zhang, Min Wu, Meijuan Ma, Bo Liu, Xuejun Zhang, Na Wei, Ting Wang, Ying Lv, Cuixiang Xu, Junkui Wang, Yulian Zhang, Fuqiang Liu
Summary: This study used a Mendelian randomisation approach to investigate the causal relationship between telomere length and aortic aneurysms. The results showed that longer telomere length can decrease the risk of aortic aneurysms, providing new insights into the potential causal association between them.
EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Endocrinology & Metabolism
Yuxia Wei, Yiqiang Zhan, Josefin E. Lofvenborg, Tiinamaija Tuomi, Sofia Carlsson
Summary: This study investigates the causal relationship between low birthweight, adult overweight/obese status, and latent autoimmune diabetes in adults (LADA) using a two-sample Mendelian randomisation design. The results suggest a negative association between low birthweight and LADA, as well as a positive association between adult BMI and LADA.
Article
Public, Environmental & Occupational Health
Gunn-Helen Moen, Robin N. Beaumont, Niels Grarup, Christine Sommer, Beverley M. Shields, Deborah A. Lawlor, Rachel M. Freathy, David M. Evans, Nicole M. Warrington
Summary: This study found a positive causal effect of maternal folate levels on offspring birthweight, while no causal effect of B12 levels on offspring birthweight was observed. The results are consistent with evidence from randomized controlled trials.
INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
(2021)
Review
Endocrinology & Metabolism
Alice E. Hughes, Andrew T. Hattersley, Sarah E. Flanagan, Rachel M. Freathy
Summary: The fetal insulin hypothesis suggests that lower birthweight and adult-onset type 2 diabetes are two phenotypes of the same genotype. Certain gene variants causing impaired pancreatic beta cell function and reduced insulin secretion result in both lower birthweight and higher risk of type 2 diabetes in later life when inherited by the fetus.
Editorial Material
Genetics & Heredity
David M. Evans, Rachel M. Freathy
Summary: This study utilized extensive pedigree data from the Icelandic population to identify genetic effects on birth weight that differ according to parental origin, and to distinguish the contributions from the maternal intrauterine environment and offspring genetics on fetal growth.
Article
Endocrinology & Metabolism
Suraj S. Nongmaithem, Robin N. Beaumont, Akshay Dedaniya, Andrew R. Wood, Babatunji-William Ogunkolade, Zahid Hassan, Ghattu Krishnaveni, Kalyanaraman Kumaran, Ramesh D. Potdar, Sirazul A. Sahariah, Murali Krishna, Chiara Di Gravio, Inder D. Mali, Alagu Sankareswaran, Akhtar Hussain, Biswajit W. Bhowmik, Abdul Kalam A. Khan, Bridget A. Knight, Timothy M. Frayling, Sarah Finer, Caroline H. D. Fall, Chittaranjan S. Yajnik, Rachel M. Freathy, Graham A. Hitman, Giriraj R. Chandak
Summary: Size at birth is influenced by various factors, including genetic effects. South Asians have a higher burden of low birth weight and cardiometabolic diseases, but studies on the genetic variations underlying these phenotypes are lacking. This study found that South Asians have smaller birth weights compared to Europeans, but the genetic effects on birth weight are similar. The study also showed that birth weight is strongly associated with body size in childhood and adolescence, while fetal genetic scores are associated with body size in childhood and head circumference, fasting glucose, and triglycerides in adults.
Letter
Endocrinology & Metabolism
Matthew C. Gage, Deirdre Harrington, Gemma V. Brierley, Rachel M. Freathy, Brendan M. Gabriel, Rachel Gibson, Alison D. McNeilly, Claire L. Meek, Lee D. Roberts
Article
Biochemistry & Molecular Biology
William D. Thompson, Robin N. Beaumont, Alan Kuang, Nicole M. Warrington, Yingjie Ji, Jess Tyrrell, Andrew R. Wood, Denise Scholtens, Bridget A. Knight, David M. Evans, William L. Lowe, Gillian Santorelli, Raq Azad, Dan Mason, Andrew T. Hattersley, Timothy M. Frayling, Hanieh Yaghootkar, Maria-Carolina Borges, Deborah A. Lawlor, Rachel M. Freathy
Summary: Recent studies have shown that higher birthweight is associated with higher adult body mass index (BMI). Alleles predisposing to greater adult adiposity may affect fetal growth and birthweight. Fetal genetic predisposition to higher metabolically favorable adiposity and BMI is associated with birthweight, with the former showing a dose-dependent association while the latter does not.
HUMAN MOLECULAR GENETICS
(2022)
Article
Biochemistry & Molecular Biology
Natalia Pervjakova, Gunn-Helen Moen, Maria-Carolina Borges, Teresa Ferreira, James P. Cook, Catherine Allard, Robin N. Beaumont, Mickael Canouil, Gad Hatem, Anni Heiskala, Anni Joensuu, Ville Karhunen, Soo Heon Kwak, Frederick T. J. Lin, Jun Liu, Sheryl Rifas-Shiman, Claudia H. Tam, Wing Hung Tam, Gudmar Thorleifsson, Toby Andrew, Juha Auvinen, Bishwajit Bhowmik, Amelie Bonnefond, Fabien Delahaye, Ayse Demirkan, Philippe Froguel, Kadri Haller-Kikkatalo, Hildur Hardardottir, Sandra Hummel, Akhtar Hussain, Eero Kajantie, Elina Keikkala, Amna Khamis, Jari Lahti, Tove Lekva, Sanna Mustaniemi, Christine Sommer, Aili Tagoma, Evangelia Tzala, Raivo Uibo, Marja Vaarasmaki, Pia M. Villa, Kare Birkeland, Luigi Bouchard, Cornelia M. Duijn, Sarah Finer, Leif Groop, Esa Hamalainen, Geoffrey M. Hayes, Graham A. Hitman, Hak C. Jang, Marjo-Riitta Jarvelin, Anne Karen Jenum, Hannele Laivuori, Ronald C. Ma, Olle Melander, Emily Oken, Kyong Soo Park, Patrice Perron, Rashmi B. Prasad, Elisabeth Qvigstad, Sylvain Sebert, Kari Stefansson, Valgerdur Steinthorsdottir, Tiinamaija Tuomi, Marie-France Hivert, Paul W. Franks, Mark McCarthy, Cecilia M. Lindgren, Rachel M. Freathy, Deborah A. Lawlor, Andrew P. Morris, Reedik Magi
Summary: The study found that gestational diabetes mellitus (GDM) and type 2 diabetes (T2D) share the same underlying pathology, but there are also genetic determinants specific to glucose regulation in pregnancy.
HUMAN MOLECULAR GENETICS
(2022)
Article
Genetics & Heredity
Suzanne Vogelezang, Jonathan P. Bradfield, Struan F. A. Grant, Janine F. Felix, Vincent W. V. Jaddoe
Summary: This study found associations between head circumference and intelligence, and highlighted the significant overlap of biological processes between early-life and adult head circumference. It also revealed the genetic correlations of early-life head circumference with intracranial volume, years of schooling, childhood and adult intelligence.
BMC MEDICAL GENOMICS
(2022)
Article
Pediatrics
Maneka Haulder, Alice E. Hughes, Robin N. Beaumont, Bridget A. Knight, Andrew T. Hattersley, Beverley M. Shields, Rachel M. Freathy
Summary: This study found that genetic scores can explain variance in birthweight in addition to easily measurable clinical variables. Maternal genetic scores contributed to explaining birthweight variance, and parental heights partially captured fetal genotype and its contribution to birthweight.
Article
Public, Environmental & Occupational Health
Caitlin S. Decina, Rhian Hopkins, Jack Bowden, Beverly M. Shields, Deborah A. Lawlor, Nicole M. Warrington, David M. Evans, Rachel M. Freathy, Robin N. Beaumont
Summary: The study revealed that higher maternal urate levels are associated with lower offspring birthweight and the causal effect of maternal urate on offspring birthweight is small. Additionally, higher urate levels are causally associated with higher systolic blood pressure, but the relationship between urate levels and offspring birthweight may be confounded.
INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
(2022)
Article
Medicine, General & Internal
Jessica O'Loughlin, Francesco Casanova, Zammy Fairhurst-Hunter, Amanda Hughes, Jack Bowden, Edward R. Watkins, Rachel M. Freathy, Iona Y. Millwood, Kuang Lin, Zhengming Chen, Liming Li, Jun Lv, Robin G. Walters, Laura D. Howe, Karoline Kuchenbaecker, Jessica Tyrrell
Summary: This study examines the relationship between body mass index (BMI) and depression in people of East Asian ancestry and finds that higher BMI is associated with lower odds of depression. The study suggests that the relationship between obesity and depression may differ based on sociocultural factors such as ancestry and place of residence.
Article
Medicine, General & Internal
Jian Zhao, Isobel D. Stewart, Denis Baird, Dan Mason, John Wright, Jie Zheng, Tom R. Gaunt, David M. Evans, Rachel M. Freathy, Claudia Langenberg, Nicole M. Warrington, Deborah A. Lawlor, Maria Carolina Borges
Summary: This study used two-sample Mendelian randomisation to explore the effect of maternal circulating amino acids on fetal growth. The results indicate that increased levels of maternal glutamine and serine are associated with higher birthweight, while increased levels of leucine and phenylalanine are associated with lower birthweight.
Article
Genetics & Heredity
Pol Sole-Navais, Christopher Flatley, Valgerdur L. Steinthorsdottir, Marc Vaudel, Julius Juodakis, Jing Chen, Triin Laisk, Abigail C. LaBella, David Westergaard, Jonas Bacelis, Ben Brumpton, Line Skotte, Maria Borges, Oyvind A. Helgeland, Anubha Mahajan, Matthias N. Wielscher, Frederick P. Lin, Catherine Briggs, Carol Wang, Gunn-Helen E. Moen, Robin R. Beaumont, Jonathan Bradfield, Abin A. Abraham, Gudmar Thorleifsson, Maiken Gabrielsen, Sisse Ostrowski, Dominika Modzelewska, Ellen M. Nohr, Elina Hypponen, Amit M. Srivastava, Octavious Talbot, Catherine Allard, Scott Williams, Ramkumar Menon, Beverley Shields, Gardar Sveinbjornsson, Huan B. Xu, Mads F. Melbye, William Lowe, Luigi Bouchard, Emily I. Oken, Ole I. Pedersen, Daniel T. Gudbjartsson, Christian Erikstrup, Erik Sorensen, Rolv Lie, Kari Teramo, Mikko T. Hallman, Thorhildur Juliusdottir, Hakon Hakonarson, Henrik L. Ullum, Andrew Hattersley, Line Sletner, Mario Merialdi, Sheryl Rifas-Shiman, Thora Steingrimsdottir, Denise A. Scholtens, Christine H. Power, Jane West, Mette A. Nyegaard, John Capra, Anne Skogholt, Per Magnus, Ole E. Andreassen, Unnur Thorsteinsdottir, Struan F. A. M. Grant, Elisabeth Qvigstad, Craig I. Pennell, Marie-France A. Hivert, Geoffrey M. Hayes, Marjo-Riitta Jarvelin, Mark I. McCarthy, Deborah Lawlor, Henriette Nielsen, Reedik Maegi, Antonis Rokas, Kristian Hveem, Kari J. Stefansson, Bjarke M. Feenstra, Pal Njolstad, Louis Muglia, Rachel Freathy, Stefan Johanson, Ge Zhang, Bo Jacobsson
Summary: The study conducted a meta-analysis and identified genetic variants associated with gestational duration and preterm delivery. It revealed the importance of maternal alleles in influencing gestational duration and the complex relationship between gestational duration and birth weight. The study also identified antagonistic pleiotropy, where maternal alleles that increase gestational duration have negative effects on birth weight.
Correction
Genetics & Heredity
Pol Sole-Navais, Christopher Flatley, Valgerdur L. Steinthorsdottir, Marc Vaudel, Julius Juodakis, Jing Chen, Triin Laisk, Abigail C. LaBella, David Westergaard, Jonas Bacelis, Ben Brumpton, Line Skotte, Maria Borges, Oyvind A. Helgeland, Anubha Mahajan, Matthias N. Wielscher, Frederick P. Lin, Catherine Briggs, Carol Wang, Gunn-Helen E. Moen, Robin R. Beaumont, Jonathan Bradfield, Abin A. Abraham, Gudmar Thorleifsson, Maiken Gabrielsen, Sisse Ostrowski, Dominika Modzelewska, Ellen M. Nohr, Elina Hypponen, Amit M. Srivastava, Octavious Talbot, Catherine Allard, Scott Williams, Ramkumar Menon, Beverley Shields, Gardar Sveinbjornsson, Huan B. Xu, Mads F. Melbye, William Lowe Jr, Luigi Bouchard, Emily I. Oken, Ole I. Pedersen, Daniel T. Gudbjartsson, Christian Erikstrup, Erik Sorensen, Rolv Lie, Kari Teramo, Mikko T. Hallman, Thorhildur Juliusdottir, Hakon Hakonarson, Henrik L. Ullum, Andrew Hattersley, Line Sletner, Mario Merialdi, Sheryl Rifas-Shiman, Thora Steingrimsdottir, Denise A. Scholtens, Christine H. Power, Jane West, Mette A. Nyegaard, John Capra, Anne Skogholt, Per Magnus, Ole E. Andreassen, Unnur Thorsteinsdottir, Struan F. A. M. Grant, Elisabeth Qvigstad, Craig I. Pennell, Marie-France A. Hivert, Geoffrey S. Hayes, Marjo-Riitta Jarvelin, Mark I. McCarthy, Deborah Lawlor, Henriette Nielsen, Reedik Magi, Antonis Rokas, Kristian Hveem, Kari J. Stefansson, Bjarke M. Feenstra, Pal Njolstad, Louis Muglia, Rachel Freathy, Stefan Johansson, Ge Zhang, Bo Jacobsson
Article
Psychiatry
Jessica O'Loughlin, Francesco Casanova, Amanda Hughes, Zammy Fairhurst-Hunter, Liming Li, Zhengming Chen, Jack Bowden, Ed Watkins, Rachel M. Freathy, Laura D. Howe, Robin G. Walters, Jessica Tyrrell
Summary: This study investigated the association between BMI and well-being in individuals of East Asian and European ancestry. The results showed that there were differences in the relationship between BMI and well-being in individuals of different ancestries, highlighting the importance of considering population-specific factors.
TRANSLATIONAL PSYCHIATRY
(2023)