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Mendelian randomisation analysis of clustered causal effects of body mass on cardiometabolic biomarkers

Susana Conde, Xiaoguang Xu, Hui Guo, Markus Perola, Teresa Fazia, Luisa Bernardinelli, Carlo Berzuini
2018 BMC Bioinformatics  
In particular, our illustrative analysis addresses the question whether body mass, as measured by body mass index (BMI), exerts a causal effect on the concentrations of a collection of 137 cardiometabolic  ...  Recent advances in data analysis methods based on principles of Mendelian Randomisation, such as Egger regression and the weighted median estimator, add to the researcher's ability to infer cause-effect  ...  as well as the HighPerformance Computing (HPC) cluster in the University of Manchester, United Kingdom.  ... 
doi:10.1186/s12859-018-2178-2 pmid:30066639 pmcid:PMC6069804 fatcat:nz75buohnbaatd3hsslautm2p4

Prioritising Risk Factors for Type 2 Diabetes: Causal Inference through Genetic Approaches

Laura B. L. Wittemans, Luca A. Lotta, Claudia Langenberg
2018 Current Diabetes Reports  
Genetic approaches are increasingly being used to infer causality, and in this review, we discuss how genetic discoveries have shaped our understanding of the causal role of factors associated with T2D  ...  Purpose of the Review Causality has been demonstrated for few of the many putative risk factors for type 2 diabetes (T2D) emerging from observational epidemiology.  ...  Body mass index as a modifiable risk factor for type 2 diabetes: refining and understanding causal estimates using Mendelian randomisation.  ... 
doi:10.1007/s11892-018-1009-1 pmid:29779155 pmcid:PMC5960479 fatcat:tiw6we76brgz3eibua7cffpxe4

Associations between weight change and biomarkers of cardiometabolic risk in South Asians: secondary analyses of the PODOSA trial

P Welsh, G Cezard, J M Gill, S Wallia, A Douglas, A Sheikh, S H Wild, J Tuomilehto, J McKnight, G Murray, R Bhopal, M E Lean (+1 others)
2016 International Journal of Obesity  
Like the Mendelian randomisation study, we show that the effect of modest weight loss on cardiometabolic biomarkers is small, and patients must be encouraged to prevent weight gain or to maximise weight  ...  We investigated the effect of a lifestyle intervention on biomarkers in the randomised groups.  ... 
doi:10.1038/ijo.2016.35 pmid:26927315 pmcid:PMC4892347 fatcat:ecog5a3s4bfobgbn5dbw3tsjbq

Genome-wide and Mendelian randomisation studies of liver MRI yield insights into the pathogenesis of steatohepatitis

Constantinos A Parisinos, Henry R Wilman, E Louise Thomas, Matt Kelly, Rowan C Nicholls, John McGonigle, Stefan Neubauer, Aroon D Hingorani, Riyaz S Patel, Harry Hemingway, Jimmy D Bell, Rajarshi Banerjee (+1 others)
2020 Journal of Hepatology  
Third, we used Mendelian randomisation to test the causal effects of 24 predominantly metabolic traits on liver cT1 measures.  ...  Second, we explored the effects of the cT1 variants on liver blood tests, and a range of metabolic traits and diseases.  ...  We used 2-sample Mendelian randomisation analysis to investigate the causal effects of metabolic traits on liver cT1.  ... 
doi:10.1016/j.jhep.2020.03.032 pmid:32247823 pmcid:PMC7372222 fatcat:cqd3etg7mjhjzobauubb6d5osq

Effects of adiposity on the human plasma proteome: observational and Mendelian randomisation estimates

Lucy J. Goudswaard, Joshua A. Bell, David A. Hughes, Laura J. Corbin, Klaudia Walter, George Davey Smith, Nicole Soranzo, John Danesh, Emanuele Di Angelantonio, Willem H. Ouwehand, Nicholas A. Watkins, David J. Roberts (+3 others)
2021 International Journal of Obesity  
This study aimed to estimate effects of body mass index (BMI) on an extensive set of circulating proteins.  ...  These were complemented by Mendelian randomisation (MR) analyses using a genetic risk score (GRS) comprised of 654 BMI-associated polymorphisms from a recent genome-wide association study (GWAS) of adult  ...  Despite MR studies supporting a causal role of adiposity for cardiometabolic diseases, and randomised trials supporting the effectiveness of weight loss in reducing disease risk [15] , the molecular footprint  ... 
doi:10.1038/s41366-021-00896-1 pmid:34226637 pmcid:PMC8455324 fatcat:et7hyk5txfenhj4cbacgzrc6tq

The CHRNA5–A3–B4 Gene Cluster and Smoking: From Discovery to Therapeutics

Glenda Lassi, Amy E. Taylor, Nicholas J. Timpson, Paul J. Kenny, Robert J. Mather, Tim Eisen, Marcus R. Munafò
2016 Trends in Neurosciences  
The CHRNA5-CHRNA3-CHRNB4 gene cluster on chromosome 15 (at 15q25) encodes three (/3, /5, b4) of the eleven (/2-7, /9, /10, b2-4) neuronal nAChR (Figure 2A ) subunits.  ...  , rs1051730 is highly correlated with rs16969968 in CHRNA5, a missense mutation that results in the substitution of aspartate (D) to asparagine (N) at the 398th amino acid  ...  Use of this gene cluster in Mendelian randomisation analyses is enabling us to investigate the causal effects of tobacco use.  ... 
doi:10.1016/j.tins.2016.10.005 pmid:27871728 pmcid:PMC5152594 fatcat:66wmxqlh2rbppj5i7ogtuxglhq

Effects of adiposity on the human plasma proteome: Observational and Mendelian randomization estimates [article]

Lucy J Goudswaard, Joshua J Bell, David A Hughes, Laura J Corbin, Klaudia Walter, George Davey Smith, Nicole Soranzo, John Danesh, Emanuele Di Angelantonio, Willem H Ouwehand, Nicholas A Watkins, David J Roberts (+3 others)
2020 medRxiv   pre-print
This study aimed to estimate effects of adiposity, proxied by body mass index (BMI), on an extensive set of circulating proteins using both observational and genetically informed analyses.  ...  MR analyses provided further evidence for a causal relationship between BMI and a range of measured proteins (eight in this analysis achieved P <1.4x10-5) including a strong relationship with leptin levels  ...  Despite MR studies supporting a causal role of adiposity for cardiometabolic diseases, and randomised trials supporting the effectiveness of weight loss in reducing disease risk (16) , the molecular footprint  ... 
doi:10.1101/2020.06.01.20119081 fatcat:2en6jaz3ubflfm3vxcdvayyawy

Metabolic phenotyping and cardiovascular disease: an overview of evidence from epidemiological settings

Aikaterini Iliou, Emmanuel Mikros, Ibrahim Karaman, Freya Elliott, Julian L Griffin, Ioanna Tzoulaki, Paul Elliott
2021 Heart  
Integration of metabolomic with genomic data can provide new evidence for involved biochemical pathways and potential for causality using Mendelian randomisation.  ...  The clinical utility of metabolic biomarkers for cardiovascular risk stratification in healthy individuals has not yet been established.  ...  effect on CHD risk using Mendelian randomisation analysis Prospective cohort study: Bruneck study 90 CVD events LC-MS shotgun lipidomics, 135 lipid species Individual species of cholesterol esters, LPCs  ... 
doi:10.1136/heartjnl-2019-315615 pmid:33608305 fatcat:eqkrn4cbxve6vfwryby57svoyi

Genome-wide association study provides new insights into the genetic architecture and pathogenesis of heart failure [article]

Sonia Shah, Albert Henry, Carolina Roselli, Honghuang Lin, Garðar Sveinbjörnsson, Ghazaleh Fatemifar, Åsa K Hedman, Jemma B Wilk, Michael P Morley, Mark D Chaffin, Anna Helgadottir, Niek Verweij (+137 others)
2019 bioRxiv   pre-print
effects for atrial fibrillation, body mass index, hypertension and triglycerides.  ...  Using Mendelian randomisation analysis we provide new evidence supporting previously equivocal causal roles for several HF risk factors identified in observational studies, and demonstrate CAD-independent  ...  We found a standard deviation increment of body mass index (BMI) (equivalent to 4. Figure 4 . 4 Conditional Mendelian randomisation analyses of HF risk factors.  ... 
doi:10.1101/682013 fatcat:5ztsn6aqvjgnheqid2sphkzqxu

Genetic insights into cardiometabolic risk factors

John B Whitfield
2014 Clinical biochemist reviews  
Some loci show unexpected effects on multiple markers or diseases.  ...  Large GWAS have been published for coronary heart disease and Type 2 diabetes, and also for associated biomarkers or risk factors including body mass index, lipids, C-reactive protein, urate, liver function  ...  This has led to the use of genetic information to perform a type of instrumental variable analysis known (rather inaccurately) as Mendelian Randomisation (MR).  ... 
pmid:24659834 pmcid:PMC3961996 fatcat:gb7tfh4p4jhhrfkrwnejbpr7oa

Obesity genetics and cardiometabolic health: Potential for risk prediction

Dharambir K. Sanghera, Cynthia Bejar, Sonali Sharma, Rajeev Gupta, Piers R. Blackett
2019 Diabetes, obesity and metabolism  
The increasing burden of obesity worldwide and its effect on cardiovascular disease (CVD) risk is an opportunity for evaluation of preventive approaches.  ...  A futuristic model depends on harnessing the predictive power of plausible genetic variants, phenotype reversibility, and effective therapeutic choices based on genotype-phenotype interactions.  ...  of Oklahoma.  ... 
doi:10.1111/dom.13641 pmid:30667137 pmcid:PMC6530772 fatcat:73y7ycb7ujgfrfpjswxj267p5y

48th European Mathematical Genetics Meeting (EMGM) 2020

Zoltan Kutalik
2020 Human Heredity  
Detection of true biological pleiotropic locus, instead of mediated or spurious ones, may inform on the etiology of complex diseases as well as on their categorization.  ...  of European ancestry based on the 1000 Genomes project.  ...  MR methods (apparent causal effect of body mass index on educational attainment may be driven by a strong ignored confounder).  ... 
doi:10.1159/000507248 pmid:32268327 fatcat:3aneluafpnes3a2ayzn53uffca

Composite trait Mendelian Randomization reveals distinct metabolic and lifestyle consequences of differences in body shape [article]

Jonathan Allen Sulc, Anthony Sonrel, Ninon Mounier, Chiara Auwerx, Eirini Marouli, Liza Darrous, Bogdan Draganski, Tuomas O Kilpeläinen, Peter K Joshi, Ruth Loos, Zoltán Kutalik
2020 medRxiv   pre-print
analysis to reveal four major independent axes of genetically driven variation in body shape and size: overall body size, adiposity, predisposition to abdominal fat deposition, and lean mass.  ...  As its genetic determinants have become increasingly elucidated, it has become feasible to investigate its health consequences via Mendelian randomisation (MR).  ...  Mendelian randomization We used inverse-variance weighted (IVW) Mendelian randomization (MR) to estimate causal effects of body traits and PCs on all non-body traits, as well as the reverse.  ... 
doi:10.1101/2020.09.03.20187567 fatcat:4ajjnvgfy5atngxz5xt6rk4grq

Mendelian Randomization analysis of the causal effect of adiposity on hospital costs

Padraig Dixon, William Hollingworth, Sean Harrison, Neil M. Davies, George Davey Smith
2020 Journal of Health Economics  
Estimates of the marginal effect of measures of adiposity such as body mass index (BMI) on healthcare costs are important for the formulation and evaluation of policies targeting adverse weight profiles  ...  We use a novel identification strategy exploiting Mendelian Randomization - random germline genetic variation modelled using instrumental variables - to identify the causal effect of BMI on inpatient hospital  ...  Acknowledgments The authors acknowledge helpful comments on this work from seminar participants at Cambridge, Cornell, Manchester, Newcastle and Oxford, and to conference participants at the Winter 2019  ... 
doi:10.1016/j.jhealeco.2020.102300 pmid:32014825 pmcid:PMC7188219 fatcat:quaj6izp75e7ti6vw5e2h3cqyq

DNA methylation signatures associated with cardiometabolic risk factors in children from India and The Gambia: results from the EMPHASIS study

Elie Antoun, Prachand Issarapu, Chiara di Gravio, Smeeta Shrestha, Modupeh Betts, Ayden Saffari, Sirazul A. Sahariah, Alagu Sankareswaran, Manisha Arumalla, Andrew M. Prentice, Caroline H. D. Fall, Matt J. Silver (+14 others)
2022 Clinical Epigenetics  
Conclusion This study identified cardiometabolic biomarkers associated with differential DNAm in Indian and Gambian children.  ...  We identified significant cis-methQTLs at three LDL-Cholesterol-associated dmCpGs in Gambians; however, methylation did not mediate genotype effects on the CMD outcomes.  ...  We also thank members of the laboratory and field teams working in both countries.  ... 
doi:10.1186/s13148-021-01213-3 pmid:35000590 pmcid:PMC8744249 fatcat:a66vrwc3fvcpdemfp22tbu3z6u
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