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Mendelian randomisation analysis of clustered causal effects of body mass on cardiometabolic biomarkers
2018
BMC Bioinformatics
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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
2018
Current Diabetes Reports
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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
2016
International Journal of Obesity
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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
2020
Journal of Hepatology
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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
2021
International Journal of Obesity
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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
2016
Trends in Neurosciences
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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]
2020
medRxiv
pre-print
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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
2021
Heart
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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]
2019
bioRxiv
pre-print
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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
2014
Clinical biochemist reviews
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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
2019
Diabetes, obesity and metabolism
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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
2020
Human Heredity
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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]
2020
medRxiv
pre-print
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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
2020
Journal of Health Economics
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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
2022
Clinical Epigenetics
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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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