scholarly journals Impact of body composition on COVID-19 susceptibility and severity: a two-sample multivariable Mendelian randomization study

2020 ◽  
Author(s):  
Dennis Freuer ◽  
Jakob Linseisen ◽  
Christa Meisinger
Keyword(s):  
Body Composition ◽  
Body Fat ◽  
Abdominal Obesity ◽  
Mendelian Randomization ◽  
P Value ◽  
Genome Wide Association Studies ◽  
Obese People ◽  
Mediation Effects ◽  
Causal Impact ◽  
The Impact

ABSTRACTObjectivesRecent studies suggested obesity to be a possible risk factor for COVID-19 disease in the wake of the coronavirus (SARS-CoV-2) infection. However, the causality and especially the role of body fat distribution in this context is still unclear. Thus, using a univariable as well as multivariable two-sample Mendelian randomization (MR) approach, we investigated for the first time the causal impact of body composition on the susceptibility and severity of COVID-19.MethodsAs indicators of overall and abdominal obesity we considered the measures body mass index (BMI), waist circumference (WC), and trunk fat ratio (TFR). Summary statistics of genome-wide association studies (GWASs) for these body composition measures were drawn from the GIANT consortium and UK Biobank, while for susceptibility and severity due to COVID-19 disease data from the COVID-19 Host Genetics Initiative was used. Total and direct causal effect estimates were calculated using Single Nucleotide Polymorphisms (SNPs), sensitivity analyses were done applying several robust MR techniques and mediation effects of type 2 diabetes (T2D) and cardiovascular diseases (CVD) were investigated within multivariable MR analyses.ResultsGenetically predicted BMI was strongly associated with both, susceptibility (OR=1.31 per 1 SD increase; 95% CI: 1.15–1.50; P-value=7.3·10−5) and hospitalization (OR=1.62 per 1 SD increase; 95% CI: 1.33–1.99; P-value=2.8·10−6) even after adjustment for genetically predicted visceral obesity traits. These associations were neither mediated substantially by T2D nor by CVD. Finally, total but not direct effects of visceral body fat on outcomes could be detected.ConclusionsThis study provides strong evidence for a causal impact of overall obesity on the susceptibility and severity of COVID-19 disease. The impact of abdominal obesity was weaker and disappeared after adjustment for BMI. Therefore, obese people should be regarded as a high-risk group. Future research is necessary to investigate the underlying mechanisms linking obesity with COVID-19.

scholarly journals What multiple Mendelian randomization approaches reveal about obesity and gout

2021 ◽  
Author(s):  
Charleen D. Adams ◽  
Brian Boutwell
Keyword(s):  
Observational Studies ◽  
Mendelian Randomization ◽  
Association Studies ◽  
Hdl Cholesterol ◽  
P Value ◽  
Genome Wide Association Studies ◽  
Cholesterol Levels ◽  
Genome Wide ◽  
The Impact ◽  
Apparent Ability

Background/Objectives: Gout is a painful arthritic disease. A robust canon of observational literature suggests strong relationships between obesity, high urate levels, and gout. But findings from observational studies can be fraught with confounding and reverse causation. They can conflict with findings from Mendelian randomization (MR), designed to tackle these biases. We aimed to determine whether the relationships between obesity, higher urate levels, and gout were causal using multiple MR approaches, including an investigation of how other closely related traits, LDL, HDL cholesterol, and triglyceride levels fit into the picture. Subjects/Methods: Summary results from genome-wide association studies of the five above-mentioned traits were extracted and used to perform two-sample (univariable, multivariable, and two-step) MR and MR mediation analysis. Results Obesity increased urate (beta=0.127; 95% CI=0.098, 0.157; P-value=1.2E-17) and triglyceride levels (beta=0.082; 95% CI=0.065, 0.099; P-value=1.2E-21) and decreased HDL cholesterol levels (beta=-0.083; 95% CI=-0.101, -0.065; P-value=2.5E-19). Higher triglyceride levels increased urate levels (beta=0.198; 95% CI=0.146, 0.251; P-value=8.9E-14) and higher HDL levels decreased them (beta=-0.109; 95% CI=-0.148, -0.071; P-value=2.7E-08). Higher urate levels (OR=1.030; 95% CI=1.028, 1.032; P-value=1.1E-130) and obesity caused gout (OR=1.003; 95% CI=1.001, 1.004; P-value=1.3E-04). The mediation MR of obesity on gout with urate levels as a mediator revealed, however, that essentially all of the effect of obesity on gout is mediated through urate. The impact of obesity on LDL cholesterol was null (beta=-0.011; 95% CI=-0.030, 0.008; P-value=2.6E-01), thus it was not included in the multivariable MR. The multivariable MR of obesity, HDL cholesterol, and triglycerides on urate levels revealed that obesity has an effect on urate levels even when accounting for HDL cholesterol and triglyceride levels. Conclusions: Obesity impacts gout indirectly by influencing urate levels and possibly other traits, such as triglycerides, that increase urate levels. Obesity's impact on urate is exacerbated by its apparent ability to decrease HDL cholesterol. 

Abstract 15527: Association Between Adrenergic Receptor Modulation and the Risk of Heart Failure: A Two-sample Mendelian Randomization Study

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Claire Baudier ◽  
Françoise Fougerousse ◽  
Amand F Schmidt ◽  
Folkert W Asselbergs ◽  
Mickael Guedj ◽  
...  
Keyword(s):  
Heart Failure ◽  
Mendelian Randomization ◽  
Association Studies ◽  
P Value ◽  
Sample Population ◽  
Genome Wide Association Studies ◽  
Receptor Modulation ◽  
Genome Wide ◽  
Genes Encoding ◽  
The Impact

Introduction: The impact of the sympathetic nervous system (SNS) modulation on the risk of heart failure (HF) outside of ß1 receptor blockade remains controversial. Methods: We performed a two-sample Mendelian randomization (MR) study using common independent genetic variants located in the cis region of genes encoding the 9 SNS receptors (α1 A, B, D, α2 A, B, C and ß 1, 2 and 3) that were associated at genome-wide significance (P-value ≤ 5х10 –8 ) with blood pressure (BP) and/or heart rate (HR) in published genome-wide association studies (GWAS) available for BP and HR. Variants were filtered out by Linkage Disequilibrium clumping (LD R 2 > 0.1) and based on their minor allele frequency (MAF < 0.01). The effects of selected variants on the genetic risk of HF were extracted from a GWAS of HF from the HERMES consortium, based on a non-overlapping sample population. MR estimates were obtained using the Wald estimator for a single variant or the inverse variance weighted method for multiple variants. Results: 542,362 controls and 40,805 HF cases were evaluated. Independent variants in genes encoding 4 SNS receptors associated with BP or HR were identified as follows: α1A (diastolic BP), α2B (diastolic BP and HR), ß1 and ß2 (diastolic and systolic BP). MR analysis of α1A and ß1, weighted by their effects on diastolic BP, estimated an association with a higher risk of HF, while α2B variants were associated with a lower risk. We found no evidence for an effect of ß2. A similar relationship with systolic BP was found for ß1 and ß2. HR increasing effect of α2B variants was associated with a decreased odd of HF. Conclusions: Mindful of pleiotropic effects, these findings are consistent with the known benefits of ß1 blockade in HF and support a similar role for α1A blockade; conversely, they suggest a detrimental lowering effect of BP and HR through α2B modulation that deserves further studies. No evidence for a role of ß2 in HF was found.

scholarly journals Age, abdominal obesity, and glycated hemoglobin are associated with carotid atherosclerosis in type 2 diabetes patients with nonalcoholic fatty liver disease

2015 ◽  
Vol 17 (3) ◽  
pp. 300 ◽  
Author(s):  
Cristina Alina Silaghi ◽  
Horatiu Silaghi ◽  
Anca Elena Craciun ◽  
Anca Farcas ◽  
Horatiu Alexandru Colosi ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Body Composition ◽  
Liver Disease ◽  
Fatty Liver ◽  
Abdominal Obesity ◽  
Fatty Liver Disease ◽  
Carotid Atherosclerosis ◽  
Alcoholic Fatty Liver ◽  
The Impact

Aim: The aim of this study was to evaluate the impact of clinical parameters and indices of body composition on the rela- tion between non-alcoholic fatty liver disease (NAFLD) and carotid intima-media thickness (cIMT), in a type 2 diabetes mel- litus population (T2DM). Material and methods: We retrospectively enrolled 336 T2DM outpatients who regularly attended Regina Maria Clinic in Cluj. Clinical, anthropometric and biochemical parameters were measured. Ultrasonography (US) was used to assess hepatic steatosis (HS) in all patients and cIMT in 146 subjects. Body composition was assessed by bioelectric impedance (BIA, InBody 720) in all patients. Results: cIMT was correlated with age (r=0.25; p=0.004), systolic blood pressure (r=0.18; p=0.041), glycated haemoglobin A1C (HbA1C, r=0.20; p=0.04), and with coronary artery disease (r=0.20; p=0.007). HS did not correlate with cIMT (r=0.04; p=0.64). cIMT was correlated with visceral fatty area (VFA, r=0.18; p=0.014) but not with other indices of body composition. Homeostasis model assessment for insulin resistance (HOMA-IR) was not correlated with cIMT (r=0.17; p=0.086). After multivariate analysis, age, HbA1c, and VFA were good independent predictors of cIMT (r=0.45; p˂0.001). Conclusions: These results are suggestive that in T2DM patients, fatty liver is not a direct mediator of early carotid atherosclerosis. Our data indicate that visceral fat accumulation and HbA1C are determinant factors of cIMT sugesting that controlling abdominal obesity and hyperglicemia might reduce atherosclerotic disease risk in NAFLD-T2DM subjects.

scholarly journals Boosting GWAS using biological networks: A study on susceptibility to familial breast cancer

2021 ◽  
Vol 17 (3) ◽  
pp. e1008819
Author(s):  
Héctor Climente-González ◽  
Christine Lonjou ◽  
Fabienne Lesueur ◽  
Dominique Stoppa-Lyonnet ◽  
Nadine Andrieu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Biological Networks ◽  
Familial Breast Cancer ◽  
Association Studies ◽  
P Value ◽  
Genome Wide Association Studies ◽  
Functional Relationships ◽  
Network Methods ◽  
The Impact

Genome-wide association studies (GWAS) explore the genetic causes of complex diseases. However, classical approaches ignore the biological context of the genetic variants and genes under study. To address this shortcoming, one can use biological networks, which model functional relationships, to search for functionally related susceptibility loci. Many such network methods exist, each arising from different mathematical frameworks, pre-processing steps, and assumptions about the network properties of the susceptibility mechanism. Unsurprisingly, this results in disparate solutions. To explore how to exploit these heterogeneous approaches, we selected six network methods and applied them to GENESIS, a nationwide French study on familial breast cancer. First, we verified that network methods recovered more interpretable results than a standard GWAS. We addressed the heterogeneity of their solutions by studying their overlap, computing what we called the consensus. The key gene in this consensus solution was COPS5, a gene related to multiple cancer hallmarks. Another issue we observed was that network methods were unstable, selecting very different genes on different subsamples of GENESIS. Therefore, we proposed a stable consensus solution formed by the 68 genes most consistently selected across multiple subsamples. This solution was also enriched in genes known to be associated with breast cancer susceptibility (BLM, CASP8, CASP10, DNAJC1, FGFR2, MRPS30, and SLC4A7, P-value = 3 × 10−4). The most connected gene was CUL3, a regulator of several genes linked to cancer progression. Lastly, we evaluated the biases of each method and the impact of their parameters on the outcome. In general, network methods preferred highly connected genes, even after random rewirings that stripped the connections of any biological meaning. In conclusion, we present the advantages of network-guided GWAS, characterize their shortcomings, and provide strategies to address them. To compute the consensus networks, implementations of all six methods are available at https://github.com/hclimente/gwas-tools.

scholarly journals Association of Physical Activity with Body Composition: A Mendelian Randomization Study

2021 ◽  
Author(s):  
Ferris Alaa Ramadan ◽  
Katherine Ellingson ◽  
Yann Klimentidis
Keyword(s):  
Physical Activity ◽  
Body Composition ◽  
Sedentary Behavior ◽  
Mendelian Randomization ◽  
Association Studies ◽  
Sensitivity Analyses ◽  
Genome Wide Association Studies ◽  
Protective Effects ◽  
Dietary Interventions ◽  
The Uk

Background. Studies suggest that body composition can be improved through physical activity (PA) independently of dietary interventions. A separate line of evidence suggests that PA may reduce high-risk visceral adipose tissue (VAT), without clinically meaningful weight change. Genome-wide association studies have previously identified genetic markers associated with PA behaviors and may provide an opportunity to evaluate hypothesized causal relationships with body composition. Methods. We performed a Mendelian randomization (MR) study to test the incremental benefits of various PA exposures on body composition outcomes as assessed by anthropometric indices, lean body mass (LBM) (kg), body fat (%), and VAT (kg). Genetic instruments were identified for both self-reported and accelerometer-measured PA, including sedentary behavior. Outcomes included anthropometric and dual-energy X-ray absorptiometry measures of adiposity, extracted from the UK Biobank and the largest publicly available consortia. Multivariable MR (MVMR) included educational attainment as a covariate to address potential confounding. Sensitivity analyses were evaluated for weak instrument bias and pleiotropic effects.Results. We did not identify associations between genetically-predicted sedentary behavior (self-reported or accelerometer) and body composition outcomes in MVMR analyses. All analyses for self-reported moderate PA were null for body composition outcomes, including BMI, LBM and VAT. Genetically-predicted PA at higher intensities was protective against VAT in MR and MVMR analyses of both accelerometer-measured vigorous PA (MVMR β = -0.15, 95% Confidence Interval (CI): -0.24, -0.07, p&lt;0.001) and self-reported participation in strenuous sports or other exercises (MVMR β = -0.27, 95%CI: -0.52, -0.01, p=0.034), and was robust across several sensitivity analyses. Conclusions. We did not identify evidence of a causal relationship between genetically-predicted PA and body composition, with the exception of a putatively protective effect of higher-intensity PA on VAT. Protective effects of PA against VAT may support prior evidence of biological pathways through which PA decreases risk of downstream cardiometabolic diseases.

Ultrasound Measurements of Subcutaneous Fat Thickness Are Robust Against Hydration Changes

2020 ◽  
pp. 1-6
Author(s):  
Dale R. Wagner ◽  
James D. Cotter
Keyword(s):  
Body Composition ◽  
Body Fat ◽  
Subcutaneous Fat ◽  
Hydration Status ◽  
Body Fat Percentage ◽  
Fat Percentage ◽  
Ultrasound Measurements ◽  
Subcutaneous Fat Thickness ◽  
Fat Thickness ◽  
The Impact

Ultrasound is an appealing tool to assess body composition, combining the portability of a field method with the accuracy of a laboratory method. However, unlike other body composition methods, the effect of hydration status on validity is unknown. This study evaluated the impact of acute hydration changes on ultrasound measurements of subcutaneous fat thickness and estimates of body fat percentage. In a crossover design, 11 adults (27.1 ± 10.5 years) completed dehydration and hyperhydration trials to alter body mass by approximately ±2%. Dehydration was achieved via humid heat (40 °C, 60% relative humidity) with exercise, whereas hyperhydration was via ingestion of lightly salted water. Ultrasound measurements were taken at 11 body sites before and after each treatment. Participants lost 1.56 ± 0.58 kg (−2.0 ± 0.6%) during the dehydration trial and gained 0.90 ± 0.21 kg (1.2 ± 0.2%) during the hyperhydration trial even after urination. The sum of fat thicknesses as measured by ultrasound differed by <0.90 mm across trials (p = .588), and ultrasound estimates of body fat percentage differed by <0.5% body fat. Ultrasound measures of subcutaneous adipose tissue were unaffected by acute changes in hydration status by extents beyond which are rare and overtly self-correcting, suggesting that this method provides reliable and robust body composition results even when subjects are not euhydrated.

scholarly journals Association between Infant Feeding and Early Postpartum Infant Body Composition: A Pilot Prospective Study

2009 ◽  
Vol 2009 ◽  
pp. 1-7 ◽  
Author(s):  
Alex Kojo Anderson
Keyword(s):  
Body Composition ◽  
Infant Feeding ◽  
Body Fat ◽  
Percent Body Fat ◽  
Mixed Feeding ◽  
Early Postpartum Period ◽  
Prepregnancy Weight ◽  
Early Postpartum ◽  
Infant Birth ◽  
The Impact

Research studies have produced conflicting results of the impact of breastfeeding on overweight/obesity. This study evaluated the impact of infant feeding on infant body composition. There were two groups of mother-infant pairs (exclusive breastfeeding [EBF;n=27] and mixed feeding [MF;n=13]) in this study. At baseline, participants were similar in their demographic characteristics except prepregnancy weight, where MF mothers tended to be heavier than their EBF counterparts (67.3 kg versus 59.9 kg;P=.034). Infant birth weight was slightly higher among the MF group than their EBF counterparts (3.5 kg versus 3.4 kg), although the differences were not statistically significant. At 3 months postpartum, mean infant FMI (4.1 kg/m2versus 3.8 kg/m2) and percent body fat (24.4% versus 23.1%) were slightly higher among EBF infants than MF infants. In terms of growth velocity, EBF infants gained weight faster than their MF counterparts, although the differences were not statistically significant. The findings from this study suggest that EBF may promote faster weight gain and increase in both fat mass index (FMI) and percent body fat in the early postpartum period in addition to the numerous health benefits enjoyed by the infant and the mother who exclusively breastfeeds her newborn.

scholarly journals The Impact of Strenuous Group Physical Activity on Mood States, Personal Views, Body Composition, and Markers of Myocardial Damage in Overweight/Obese Adults: The “Step-by-Step Italy’s Coast to Coast” Trek

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Claudia Mazzeschi ◽  
Natalia Piana ◽  
Daniela Capezzali ◽  
Antonella Mommi ◽  
Cristina Aiello ◽  
...  
Keyword(s):  
Body Composition ◽  
Psychological Impact ◽  
Myocardial Damage ◽  
Normal Weight ◽  
Obese Adults ◽  
Long Distance ◽  
Obese People ◽  
Obese Subjects ◽  
Relationship Of ◽  
The Impact

It is clinically relevant to understand whether it is safe to recommend to trained overweight/obese people long-distance treks and whether these experiences could have a negative psychological impact or become even dangerous exposing the trekkers to the risk of clinically silent myocardial damage. To answer these questions we have performed a quantitative/qualitative study comparing the changes in mood profiles, personal views, body composition, and plasma troponin levels of 40 overweight/obese subjects with those of 36 healthy normal weight subjects after the participation in a trek of 388 km from the Adriatic to the Tyrrhenian seas trek: the “Step by step…Italy’s coast to coast”. The results of this study demonstrate that long-distance treks are a safe activity for trained overweight/obese people which should be recommended because they improve mood, health status, and the relationship of participants with themselves and with the regular practice of exercise with effects similar to those obtained by healthy normal weight subjects.

Bicycling but not Walking Is Independently Associated With Fasting Insulin in Abdominally Obese Women

2011 ◽  
Vol 8 (6) ◽  
pp. 820-823 ◽  
Author(s):  
Erik Hemmingsson ◽  
Ulf Ekelund ◽  
Joanna Udden
Keyword(s):  
Insulin Resistance ◽  
Body Fat ◽  
Abdominal Obesity ◽  
Serum Insulin ◽  
Whole Body ◽  
Obese Women ◽  
Fasting Serum ◽  
Insulin Levels ◽  
The Impact

Background:The impact of walking and bicycling on insulin resistance (IR) in women with abdominal obesity is unclear.Methods:Pooled analysis of data from a randomized trial on physically active commuting (bicycling + walking vs walking only) in women with abdominal obesity [n = 98; age:47.3 ± 7.6 yrs; waist circumference (WC):103.1 ± 7.8 cm]. Bicycling and walking data were collected during 7 consecutive days by trip meters (Trelock FC-410) and pedometers (Yamax digiwalker SW-200) at baseline, 2, 4, and 6 months. Owing to a skew distribution we analyzed bicycling as a binary dummy variable with a 10 km/week cut-off. Fasting serum insulin and homeostatic model assessment – insulin resistance (HOMA-IR) were assessed at baseline and 6 months, as were body mass index (BMI), WC, and dual x-ray absorptiometry (DXA)-assessed % whole-body fat.Results:Increased bicycling by 10 km/wk was associated with reductions in fasting serum insulin at follow-up independent of age, treatment allocation, baseline phenotype, Δ walking, and Δ % body fat (β = −10.9, P = .042), but not HOMA-IR (β = −2.0, P = .13). Increased walking was not associated with fasting serum insulin (P = .33) or HOMA-IR (P = .44) at follow-up, after adjustment for the same covariates and Δ bicycling.Conclusion:Increased bicycling but not walking was associated with reduced insulin levels at follow-up. Bicycling may be more effective than walking for reducing insulin levels in abdominally obese women.

scholarly journals Causal Association between Serum Thyroid-Stimulating Hormone and Obesity: A Bidirectional Mendelian Randomization Study

2021 ◽  
Author(s):  
Xichang Wang ◽  
Xiaotong Gao ◽  
Yutong Han ◽  
Fan Zhang ◽  
Zheyu Lin ◽  
...  
Keyword(s):  
Mendelian Randomization ◽  
Association Studies ◽  
Epidemiological Studies ◽  
Thyroid Stimulating Hormone ◽  
Genome Wide Association Studies ◽  
Causal Association ◽  
Free Triiodothyronine ◽  
The Impact ◽  
Serum Tsh ◽  
Stimulating Hormone

Abstract Context The association between serum thyroid-stimulating hormone (TSH) and obesity traits has been investigated previously in several epidemiological studies. However, the underlying causal association has not been established. Objective To determine and analyze the causal association between serum TSH level and obesity-related traits (BMI and obesity). Design, Setting, Participants The latest genome-wide association studies (GWASs) on TSH, BMI and obesity were searched to obtain full statistics. Bidirectional two-sample Mendelian randomization (MR) was performed to explore the causal relationship between serum TSH and BMI and obesity. The inverse variance-weighted (IVW) and MR-Egger methods were used to combine the estimation for each SNP. Based on the preliminary MR results, free thyroxine (fT4) and free triiodothyronine (fT3) levels were also set as outcomes to further analyze the impact of BMI on them. Main Outcome Measures BMI and obesity were treated as the outcomes to evaluate the effect of serum TSH on them, and TSH was set as the outcome to estimate the effect of BMI and obesity on it. Results Both IVW and MR-Egger results indicated that genetically driven serum TSH did not causally lead to changes in BMI or obesity. Moreover, the IVW method showed that the TSH level could be significantly elevated by genetically predicted high BMI (β=0.038, se=0.013, p=0.004). In further MR analysis, the IVW method indicated that BMI could causally increase the fT3 (β=10.123, se=2.523, p&lt;0.001) while not significantly affecting the fT4 level. Conclusion Together with fT3, TSH can be significantly elevated by an increase in genetically driven BMI.

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