scholarly journals Assessing the role of cortisol in cancer: a wide-ranged Mendelian randomisation study

2021 ◽  
Author(s):  
Susanna C. Larsson ◽  
Wei-Hsuan Lee ◽  
Siddhartha Kar ◽  
Stephen Burgess ◽  
Elias Allara
Keyword(s):  
Mendelian Randomisation

scholarly journals Osteoarthritis: Insights Offered by the Study of Bone Mass Genetics

2021 ◽  
Vol 19 (2) ◽  
pp. 115-122
Author(s):  
A. Hartley ◽  
C. L. Gregson ◽  
L. Paternoster ◽  
J. H. Tobias
Keyword(s):  
Bone Mass ◽  
Causal Effect ◽  
Mendelian Randomisation ◽  
Mineral Density ◽  
High Bone Mass ◽  
Increased Risk ◽  
High Bone ◽  
Genetic Mechanisms ◽  
Additional Support

Abstract Purpose of Review This paper reviews how bone genetics has contributed to our understanding of the pathogenesis of osteoarthritis. As well as identifying specific genetic mechanisms involved in osteoporosis which also contribute to osteoarthritis, we review whether bone mineral density (BMD) plays a causal role in OA development. Recent Findings We examined whether those genetically predisposed to elevated BMD are at increased risk of developing OA, using our high bone mass (HBM) cohort. HBM individuals were found to have a greater prevalence of OA compared with family controls and greater development of radiographic features of OA over 8 years, with predominantly osteophytic OA. Initial Mendelian randomisation analysis provided additional support for a causal effect of increased BMD on increased OA risk. In contrast, more recent investigation estimates this relationship to be bi-directional. However, both these findings could be explained instead by shared biological pathways. Summary Pathways which contribute to BMD appear to play an important role in OA development, likely reflecting shared common mechanisms as opposed to a causal effect of raised BMD on OA. Studies in HBM individuals suggest this reflects an important role of mechanisms involved in bone formation in OA development; however further work is required to establish whether the same applies to more common forms of OA within the general population.

scholarly journals Role of obesity in smoking behaviour: Mendelian randomisation study in UK Biobank

BMJ ◽  
2018 ◽  
pp. k1767 ◽  
Author(s):  
Robert Carreras-Torres ◽  
Mattias Johansson ◽  
Philip C Haycock ◽  
Caroline L Relton ◽  
George Davey Smith ◽  
...  
Keyword(s):  
Smoking Behaviour ◽  
Mendelian Randomisation ◽  
Uk Biobank

scholarly journals 131 Aetiological role of folate deficiency in congenital heart disease: evidence from Mendelian randomisation and meta-analysis

Heart ◽  
2011 ◽  
Vol 97 (Suppl 1) ◽  
pp. A75-A75
Author(s):  
V. Mamasoula ◽  
T. Pierscionek ◽  
D. Hall ◽  
J. Palomino-Doza ◽  
A. Topf ◽  
...  
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Congenital Heart ◽  
Meta Analysis ◽  
Folate Deficiency ◽  
Mendelian Randomisation

scholarly journals Causal Inference in Psychopathology: A Systematic Review of Mendelian Randomisation Studies Aiming to Identify Environmental Risk Factors for Psychopathology

2016 ◽  
Vol a4 (1) ◽  
pp. 4-25 ◽  
Author(s):  
Jean-Baptiste Pingault ◽  
Charlotte A. M. Cecil ◽  
Joseph Murray ◽  
Marcus R Munafò ◽  
Essi Viding
Keyword(s):  
Risk Factors ◽  
Systematic Review ◽  
Causal Inference ◽  
Genetic Variants ◽  
Antisocial Behaviour ◽  
Smoking Initiation ◽  
Mendelian Randomisation ◽  
Future Directions ◽  
Effective Interventions

Psychopathology represents a leading cause of disability worldwide. Effective interventions need to target risk factors that are causally related to psychopathology. In order to distinguish between causal and spurious risk factors, it is critical to account for environmental and genetic confounding. Mendelian randomisation studies use genetic variants that are independent from environmental and genetic confounders in order to strengthen causal inference. We conducted a systematic review of studies (N = 19) using Mendelian randomisation to examine the causal role of putative risk factors for psychopathology-related outcomes including depression, anxiety, psychological distress, schizophrenia, substance abuse/antisocial behaviour, and smoking initiation. The most commonly examined risk factors in the reviewed Mendelian randomisation studies were smoking, alcohol use and body mass index. In most cases, risk factors were strongly associated with psychopathology-related outcomes in conventional analyses but Mendelian randomisation indicated that these associations were unlikely to be causal. However, Mendelian randomisation analyses showed that both smoking and homocysteine plasma levels may be causally linked with schizophrenia. We discuss possible reasons for these diverging results between conventional and Mendelian randomisation analyses and outline future directions for progressing research in ways that maximise the potential for identifying targets for intervention.

scholarly journals The total and direct effects of systolic and diastolic blood pressure on cardiovascular disease and longevity using Mendelian randomisation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Io Ieong Chan ◽  
Man Ki Kwok ◽  
C. Mary Schooling
Keyword(s):  
Blood Pressure ◽  
American Heart ◽  
Heart Association ◽  
Mendelian Randomisation ◽  
Direct Effects ◽  
Z Score ◽  
Negative Effects ◽  
Artery Disease ◽  
The Uk

AbstractThe 2017 American College of Cardiology/American Heart Association (ACC/AHA) blood pressure (BP) guidelines lowered the hypertension threshold to ≥ 130/80 mmHg, but the role of diastolic BP remains contested. This two-sample mendelian randomisation study used replicated genetic variants predicting systolic and diastolic BP applied to the UK Biobank and large genetic consortia, including of cardiovascular diseases and parental lifespan, to obtain total and direct effects. Systolic and diastolic BP had positive total effects on CVD (odds ratio (OR) per standard deviation 2.15, 95% confidence interval (CI) 1.95, 2.37 and OR 1.91, 95% CI 1.73, 2.11, respectively). Direct effects were similar for systolic BP (OR 1.83, 95% CI 1.48, 2.25) but completely attenuated for diastolic BP (1.18, 95% CI 0.97, 1.44), although diastolic BP was associated with coronary artery disease (OR 1.24, 95% CI 1.03, 1.50). Systolic and diastolic BP had similarly negative total (− 0.20 parental attained age z-score, 95% CI − 0.22, − 0.17 and − 0.17, 95% CI − 0.20, − 0.15, respectively) and direct negative effects on longevity. Our findings suggest systolic BP has larger direct effects than diastolic BP on CVD, but both have negative effects (total and direct) on longevity, supporting the 2017 ACC/AHA guidelines lowering both BP targets.

scholarly journals Impact of lung function on cardiovascular diseases and cardiovascular risk factors: a two sample bidirectional Mendelian randomisation study

Thorax ◽  
2021 ◽  
pp. thoraxjnl-2020-215600
Author(s):  
Shiu Lun Au Yeung ◽  
Maria Carolina Borges ◽  
Debbie A Lawlor ◽  
C Mary Schooling
Keyword(s):  
Risk Factors ◽  
Type 2 Diabetes ◽  
Cardiovascular Risk ◽  
Lung Function ◽  
Sensitivity Analyses ◽  
Mendelian Randomisation ◽  
Summary Statistics ◽  
Reverse Causation

IntroductionObservational studies suggested lung function is inversely associated with cardiovascular disease (CVD) although these studies could be confounded. We conducted a two sample Mendelian randomisation study using summary statistics from genome-wide association studies (GWAS) to clarify the role of lung function in CVD and its risk factors, and conversely the role of CVD in lung function.MethodsWe obtained genetic instruments for forced expiratory volume in 1 s (FEV1: 260) and forced vital capacity (FVC: 320) from publicly available UK Biobank summary statistics (n=421 986) and applied to GWAS summary statistics for coronary artery disease (CAD) (n=184 305), stroke (n=446 696), atrial fibrillation (n=1 030 836) and heart failure (n=977 320) and cardiovascular risk factors. Inverse variance weighting was used to assess the impact of lung function on these outcomes, with various sensitivity analyses. Bidirectional Mendelian randomisation was used to assess reverse causation.ResultsFEV1 and FVC were inversely associated with CAD (OR per SD increase, 0.72 (95% CI 0.63 to 0.82) and 0.70 (95%CI 0.62 to 0.78)), overall stroke (0.87 (95%CI 0.77 to 0.97), 0.90 (95% CI 0.82 to 1.00)) and some stroke subtypes. FEV1 and FVC were inversely associated with type 2 diabetes and systolic blood pressure. Sensitivity analyses produced similar findings although the association with CAD was attenuated after adjusting for height (eg, OR for 1SD FEV10.95 (0.75 to 1.19), but not for stroke or type 2 diabetes. There was no strong evidence for reverse causation.ConclusionHigher lung function likely protect against CAD and stroke.

scholarly journals Role of DNA methylation in the association of lung function with body mass index: a two-step epigenetic Mendelian randomisation study

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
André F. S. Amaral ◽  
◽  
Medea Imboden ◽  
Matthias Wielscher ◽  
Faisal I. Rezwan ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Dna Methylation ◽  
Lung Function ◽  
Body Mass ◽  
Mendelian Randomisation

Testing the role of vitamin D in response to antitumour necrosis factor α therapy in a UK cohort: a Mendelian randomisation approach

2013 ◽  
Vol 73 (5) ◽  
pp. 938-940 ◽  
Author(s):  
Annie Yarwood ◽  
Sebastien Viatte ◽  
Darren Plant ◽  
Ann W Morgan ◽  
John Isaacs ◽  
...  
Keyword(s):  
Vitamin D ◽  
Mendelian Randomisation ◽  
Factor Α ◽  
Necrosis Factor

scholarly journals Proteome-by-phenome Mendelian Randomisation detects 38 proteins with causal roles in human diseases and traits

2019 ◽  
Author(s):  
Andrew D. Bretherick ◽  
Oriol Canela-Xandri ◽  
Peter K. Joshi ◽  
David W. Clark ◽  
Konrad Rawlik ◽  
...  
Keyword(s):  
Disease Risk ◽  
Target Identification ◽  
Cardiovascular Disease Risk ◽  
Causal Role ◽  
Mendelian Randomisation ◽  
Disease Pathogenesis ◽  
Plasma Protein Concentration ◽  
Fatty Acid Binding ◽  
Specific Prediction

AbstractTarget identification remains a crucial challenge in drug development. To enable unbiased detection of proteins and pathways that have a causal role in disease pathogenesis or progression, we propose proteome-by-phenome Mendelian Randomisation (P2MR). We first detected genetic variants associated with plasma concentration of 249 proteins. We then used 64 replicated variants in two-sample Mendelian Randomisation to quantify evidence of a causal role for each protein across 846 phenotypes: this yielded 509 robust protein-outcome links. P2MR provides substantial promise for drug target prioritisation. We provide confirmatory evidence for a causal role for the proteins encoded at multiple cardiovascular disease risk loci (FGF5, IL6R, LPL, LTA), and discovered that intestinal fatty acid binding protein (FABP2) contributes to disease pathogenesis. Additionally, we find and replicate evidence for a causal role of tyrosine-protein phosphatase non-receptor type substrate 1 (SHPS1; SIRPA) in schizophrenia. Our results provide specific prediction of the effects of changes of plasma protein concentration on complex phenotypes in humans.

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