scholarly journals Metabolic and lifestyle factors in relation to senile cataract: a Mendelian randomization study

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Shuai Yuan ◽  
Alicja Wolk ◽  
Susanna C. Larsson
Keyword(s):  
Standard Deviation ◽  
Odds Ratio ◽  
Mendelian Randomization ◽  
Coffee Consumption ◽  
Smoking Initiation ◽  
Lifestyle Factors ◽  
Senile Cataract ◽  
Nucleotide Polymorphisms ◽  
Standard Deviation Increase ◽  
Increased Risk

AbstractWe conducted a Mendelian randomization study to determine the associations of body mass index (BMI), type 2 diabetes (T2D), systolic blood pressure (SBP), coffee and alcohol consumption and smoking initiation with senile cataract. Independent single nucleotide polymorphisms associated with the metabolic and lifestyle factors at the p < 5 × 10–8 were selected as instrument variables. Summary-level data for senile cataract were obtained from the FinnGen consortium (20,157 cases and 154,905 non-cases) and UK Biobank study (6332 cases and 354,862 non-cases). Higher genetically predicted BMI and SBP and genetic predisposition to T2D and smoking initiation were associated with an increased risk of senile cataract. The combined odds ratios were 1.19 (95% confidence interval (CI) 1.09–1.29; p < 0.001) per one standard deviation increase in BMI (~ 4.8 kg/m2), 1.13 (95% CI 1.04–1.23; p = 0.004) per 10 mmHg increase in SBP, 1.06 (95% CI 1.03–1.09; p < 0.001) per one unit increase in log-transformed odds ratio of T2D, and 1.19 (95% CI 1.10–1.29; p < 0.001) per one standard deviation increase in prevalence of smoking initiation. Genetically predicted coffee consumption showed a suggestive association with senile cataract (odds ratio per 50% increase, 1.18, 95% CI 1.00–1.40; p = 0.050). This study suggests causal roles of obesity, T2D, SBP and smoking in senile cataract.

P–374 Investigating causality of risk factors for miscarriage – a Mendelian randomization analysis

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
J Painter ◽  
T Laisk ◽  
C Lindgren ◽  
S Medland
Keyword(s):  
Risk Factors ◽  
Body Mass Index ◽  
Risk Factor ◽  
Instrumental Variables ◽  
Genetic Variants ◽  
Odds Ratio ◽  
Mendelian Randomization ◽  
Recurrent Miscarriage ◽  
Coffee Consumption ◽  
Smoking Initiation

Abstract Study question Do modifiable risk factors such as smoking, alcohol or coffee consumption, and adiposity causally increase the risk of sporadic or recurrent miscarriage? Summary answer We found evidence for a causal relationship between smoking initiation and sporadic miscarriage, but not for any other risk factor tested. What is known already Miscarriage is estimated to end between 10–25% of clinically confirmed pregnancies, and many observational studies have suggested numerous lifestyle factors, such as coffee and alcohol consumption, smoking and increased adiposity, may increase miscarriage risk. However, results are not always consistent across studies, and definitive causal relationships between various risk factors and miscarriage have not yet been demonstrated. Mendelian randomization utilizes genetic variants significantly associated with heritable risk factors (i.e. at P-values &lt;5x10–8 in large genome-wide association studies) as instrumental variables to investigate causality of risk factors in population health outcomes. Study design, size, duration We conducted two-sample Mendelian randomization analyses to investigate causality of smoking (initiation and quantity), alcohol and coffee consumption (quantity), and adiposity (body mass index and waist-hip ratio) in sporadic and recurrent miscarriage. Data included in this study were taken from previously published summary genetic association statistics (betas, standard errors and P-values) from large-scale genome-wide association studies (GWAS) for each risk factor, and from our recently published GWAS of sporadic and recurrent miscarriage. Participants/materials, setting, methods Instrumental variables were constructed using 5–306 genetic variants significantly associated with the listed risk factors in published GWAS (minimum N = 178,000 individuals). Two instrumental variables were constructed per risk factor using data from different GWAS. Associations of the instrumental variables with miscarriage were investigated using summary association data from women of European ancestry included in our miscarriage GWAS, including 49,996 sporadic miscarriage cases and 174,109 female controls, and 750 recurrent miscarriage cases and 150,215 female controls. Main results and the role of chance We found a significant association between sporadic miscarriage and the instrumental variables for two smoking measures: smoking initiation (inverse variance weighted Odds Ratio = 1.17, 95% confidence intervals = 1.10–1.24, P = 2.7 x 10–07) and lifetime smoking (inverse variance weighted Odds Ratio = 1.22, 95% confidence intervals 1.11–1.35, P = 4.2x10–5). No other risk factors (smoking quantity, coffee or alcohol consumption, or BMI or waist-hip ratio) were associated with either sporadic or recurrent miscarriage. A priori power calculations considering the amount of phenotypic variance in each risk factor explained by the associated SNPs suggested our analysis to have at least 75% power to detect an association with Odds Ratio of 1.2 with sporadic miscarriage for analyses of body mass index, waist hip ratio and smoking initiation, quantity and the lifetime smoking measure, but that the alcohol and coffee consumption analyses were underpowered (4.9% and 48%, respectively). All analyses were underpowered for recurrent miscarriage given the small case sample size (N = 750). Limitations, reasons for caution While data utilised here come from large-scale GWAS including 1000s of individuals, genetic variants significantly associated with each risk factor currently explain small percentages (0.02–6%) of the variance in each trait. Larger GWAS for specific risk factors, and for sporadic and recurrent miscarriage, are required to clarify some published associations. Wider implications of the findings: We find no evidence of a causal link between adiposity and miscarriage, indicating that observational findings of increased miscarriage risk with increasing body mass index require further explanation. Significant associations between measures of ever-smoking and sporadic miscarriage highlights that no amount of smoking is safe in regards to miscarriage risk. Trial registration number Not applicable

scholarly journals Serum Parathyroid Hormone, 25-Hydroxyvitamin D, and Risk of Alzheimer’s Disease: A Mendelian Randomization Study

Nutrients ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 1243 ◽  
Author(s):  
Susanna Larsson ◽  
Matthew Traylor ◽  
Hugh Markus ◽  
Karl Michaëlsson
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Parathyroid Hormone ◽  
Standard Deviation ◽  
Odds Ratio ◽  
Mendelian Randomization ◽  
Serum Parathyroid Hormone ◽  
Standard Deviation Increase ◽  
Hydroxyvitamin D ◽  
25 Hydroxyvitamin D

We conducted Mendelian randomization analyses to investigate the associations of serum parathyroid hormone (S-PTH) and serum 25-hydroxyvitamin D (S-25OHD) concentrations with Alzheimer’s disease (AD). Five and seven single nucleotide polymorphisms associated with S-PTH and S-25OHD concentrations, respectively, were used as instrumental variables. Data for AD were acquired from the International Genomics of Alzheimer’s Project (17,008 AD cases and 37,154 controls). Genetically higher S-PTH concentrations were not associated with AD (odds ratio per standard deviation increase in S-PTH = 1.11; 95% CI 0.97–1.26; p = 0.12). In contrast, all seven 25OHD-increasing alleles were inversely associated with AD and two of the associations were statistically significant (p < 0.05). The odds ratio of AD per genetically-predicted one standard deviation increase in S-25OHD was 0.86 (95% CI 0.78–0.94; p = 0.002). This study provides evidence that vitamin D may play a role in AD but found no significant association between S-PTH and AD.

EXPRESS: Effect of genetic liability to visceral adiposity on stroke and its subtypes: a Mendelian randomization study

2021 ◽  
pp. 174749302110062
Author(s):  
Bin Yan ◽  
Jian Yang ◽  
Li Qian ◽  
Fengjie Gao ◽  
Ling Bai ◽  
...  
Keyword(s):  
Sensitivity Analysis ◽  
Ischemic Stroke ◽  
Genome Wide Association Study ◽  
Mendelian Randomization ◽  
Visceral Adiposity ◽  
Large Artery ◽  
Nucleotide Polymorphisms ◽  
Genetic Liability ◽  
A Genome ◽  
Increased Risk

Background: Observational studies have found an association between visceral adiposity and stroke. Aims: The purpose of this study was to investigate the role and genetic effect of visceral adipose tissue (VAT) accumulation on stroke and its subtypes. Methods: In this two-sample Mendelian randomization (MR) study, genetic variants (221 single nucleotide polymorphisms; P<5×10-8) using as instrumental variables for MR analysis was obtained from a genome-wide association study (GWAS) of VAT. The outcome datasets for stroke and its subtypes were obtained from the MEGASTROKE consortium (up to 67,162 cases and 453,702 controls). MR standard analysis (inverse variance weighted method) was conducted to investigate the effect of genetic liability to visceral adiposity on stroke and its subtypes. Sensitivity analysis (MR-Egger, weighted median, MR-PRESSO) were also utilized to assess horizontal pleiotropy and remove outliers. Multi-variable MR analysis was employed to adjust potential confounders. Results: In the standard MR analysis, genetically determined visceral adiposity (per 1 SD) was significantly associated with a higher risk of stroke (odds ratio [OR] 1.30; 95% confidence interval [CI] 1.21-1.41, P=1.48×10-11), ischemic stroke (OR 1.30; 95% CI 1.20-1.41, P=4.01×10-10), and large artery stroke (OR 1.49; 95% CI 1.22-1.83, P=1.16×10-4). The significant association was also found in sensitivity analysis and multi-variable MR analysis. Conclusions: Genetic liability to visceral adiposity was significantly associated with an increased risk of stroke, ischemic stroke, and large artery stroke. The effect of genetic susceptibility to visceral adiposity on the stroke warrants further investigation.

scholarly journals Gallstone disease, diabetes, calcium, triglycerides, smoking and alcohol consumption and pancreatitis risk: Mendelian randomization study

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Shuai Yuan ◽  
Edward L. Giovannucci ◽  
Susanna C. Larsson
Keyword(s):  
Type 2 Diabetes ◽  
Chronic Pancreatitis ◽  
Alcohol Consumption ◽  
Mendelian Randomization ◽  
Gallstone Disease ◽  
Smoking Initiation ◽  
Disease Type ◽  
Uk Biobank ◽  
Increased Risk

AbstractWe conducted a Mendelian randomization study to determine the potential causal associations of gallstone disease, diabetes, serum calcium, triglyceride levels, smoking and alcohol consumption with acute and chronic pancreatitis. Genetic variants associated with the exposures at p < 5 × 10−8 were selected from corresponding genome-wide association studies. Summary-level data for pancreatitis were obtained from the FinnGen consortium and UK Biobank. Univariable and multivariable Mendelian randomization analyses were performed and results from FinnGen and UK Biobank were combined using the fixed-effects meta-analysis method. Genetic predisposition to gallstone disease, type 2 diabetes and smoking initiation was associated with an increased risk of acute pancreatitis. The combined odds ratios (ORs) were 1.74 (95% confidence interval (CI), 1.57, 1.93) for gallstone disease, 1.14 (95% CI, 1.06, 1.21) for type 2 diabetes and 1.56 (95% CI, 1.32, 1.83) for smoking initiation. The association for type 2 diabetes attenuated after adjustment for gallstone disease. Genetic predisposition to gallstone disease and smoking initiation as well as higher genetically predicted serum calcium and triglyceride levels were associated with an increased risk of chronic pancreatitis. The combined ORs of chronic pancreatitis were 1.27 (95% CI, 1.08, 1.50) for gallstone disease, 1.86 (95% CI, 1.43, 2.43) for smoking initiation, 2.20 (95% CI, 1.30, 3.72) for calcium and 1.47 (95% CI, 1.23, 1.76) for triglycerides. This study provides evidence in support that gallstone disease, type 2 diabetes, smoking and elevated calcium and triglyceride levels are causally associated with the risk of acute or chronic pancreatitis.

scholarly journals Coffee Consumption and Cardiovascular Diseases: A Mendelian Randomization Study

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2218
Author(s):  
Shuai Yuan ◽  
Paul Carter ◽  
Amy M. Mason ◽  
Stephen Burgess ◽  
Susanna C. Larsson
Keyword(s):  
Cardiovascular Disease ◽  
Cardiovascular Diseases ◽  
Intracerebral Hemorrhage ◽  
Genetic Variants ◽  
Odds Ratio ◽  
Observational Studies ◽  
Mendelian Randomization ◽  
Coffee Consumption ◽  
Uk Biobank ◽  
The Uk

Coffee consumption has been linked to a lower risk of cardiovascular disease in observational studies, but whether the associations are causal is not known. We conducted a Mendelian randomization investigation to assess the potential causal role of coffee consumption in cardiovascular disease. Twelve independent genetic variants were used to proxy coffee consumption. Summary-level data for the relations between the 12 genetic variants and cardiovascular diseases were taken from the UK Biobank with up to 35,979 cases and the FinnGen consortium with up to 17,325 cases. Genetic predisposition to higher coffee consumption was not associated with any of the 15 studied cardiovascular outcomes in univariable MR analysis. The odds ratio per 50% increase in genetically predicted coffee consumption ranged from 0.97 (95% confidence interval (CI), 0.63, 1.50) for intracerebral hemorrhage to 1.26 (95% CI, 1.00, 1.58) for deep vein thrombosis in the UK Biobank and from 0.86 (95% CI, 0.50, 1.49) for subarachnoid hemorrhage to 1.34 (95% CI, 0.81, 2.22) for intracerebral hemorrhage in FinnGen. The null findings remained in multivariable Mendelian randomization analyses adjusted for genetically predicted body mass index and smoking initiation, except for a suggestive positive association for intracerebral hemorrhage (odds ratio 1.91; 95% CI, 1.03, 3.54) in FinnGen. This Mendelian randomization study showed limited evidence that coffee consumption affects the risk of developing cardiovascular disease, suggesting that previous observational studies may have been confounded.

Causal associations of obesity with chronic kidney disease and arterial stiffness: a Mendelian randomization study

2021 ◽  
Author(s):  
Chaojie Ye ◽  
Lijie Kong ◽  
Zhiyun Zhao ◽  
Mian Li ◽  
Shuangyuan Wang ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Standard Deviation ◽  
Kidney Disease ◽  
Single Nucleotide Polymorphisms ◽  
Arterial Stiffness ◽  
Genetic Risk ◽  
Mendelian Randomization ◽  
Genetic Risk Score ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide

Abstract Purpose Observational studies have associated obesity with chronic kidney disease (CKD) and arterial stiffness, but the causality remains unclear. We aimed to investigate the causality of obesity with CKD and arterial stiffness using Mendelian randomization (MR) analysis. Methods We genotyped 14 body mass index (BMI)-associated variants validated in East Asians in 11384 Chinese adults. A genetic risk score based on the 14 variants and the 14 individual single nucleotide polymorphisms were respectively used as instrumental variables (IVs). CKD was defined as estimated glomerular filtration rate &lt;60 mL/min/1.73 m 2. Arterial stiffness was defined as brachial-ankle pulse wave velocity &gt;1550 cm/s. Results Using the genetic risk score as the IV, we demonstrated causal relations of each 1-standard deviation increment in BMI with CKD (odds ratio [OR]: 2.36; 95% confidence interval [CI]: 1.11-5.00) and arterial stiffness (OR: 1.71; 95% CI: 1.22-2.39). Using the 14 single nucleotide polymorphisms individually as IVs, each 1-standard deviation increment in BMI casually associated with CKD (OR: 2.58; 95% CI: 1.39-4.79) and arterial stiffness (OR: 1.87; 95% CI: 1.24-2.81) in the inverse-variance weighted analysis, and MR-Egger regression revealed no evidence of horizontal pleiotropy (Both P for intercept≥0.34). The causality between obesity and CKD was validated in two-sample MR analysis among Europeans (681275 of Genetic Investigation of ANthropometric Traits and 133413 of CKD Genetics). Conclusions This study provided novel insights into causality of obesity with CKD and arterial stiffness, highlighting the importance of weight management for primary prevention and control of subclinical vascular diseases.

Abstract 16584: Association of Lower Height and Higher LDL-c in a Statewide Schoolchild Cholesterol Screening Program

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Lee A Pyles ◽  
Christa Lilly ◽  
Eloise Elliott ◽  
William A Neal
Keyword(s):  
Short Stature ◽  
Odds Ratio ◽  
Screening Program ◽  
Nucleotide Polymorphisms ◽  
Chi Square ◽  
Primordial Prevention ◽  
Lipid Panel ◽  
Increased Risk ◽  
Lower Height ◽  
Chi Square Analysis

Introduction: The Coronary Artery Risk Detection in Appalachian Communities (CARDIAC) Project has screened West Virginia 5th graders since 1998 to facilitate primordial prevention of coronary heart disease (CHD) in WV. LDL-c levels above 175 mg/dl in children suggest Familial Hyperlipidemia (FH) in the child’s family and a level above 160 mg/dl with history of CHD in relatives can also establish a diagnosis. Hypothesis: Based on previous adult literature, the association of lower height with higher LDL level observed in adults begins in childhood and is prominent in children with LDL in FH range. Methods: Fifth graders are screened yearly in WV schools with parental consent for Body Mass Index and lipid panel. Lipids were analyzed with respect to either short stature < 2 SD for height or comparing 1st (shortest) and 4th quartiles of the population. Statistical analysis for age- and gender-adjusted height percentiles was performed in SAS. Results: 59,386 children had lipid and height data. Mean LDL-c for 1st vs. 4th quartile of height was 94.08 mg/dl (95% Confidence Interval-CI 93.66-94.51) vs. 90.03 mg/dl (CI 89.65-90.42). First quartile of height students had average 4.05 mg/dl higher LDL-c (95% CI 3.48 -4.62 mg/dl). 4398 children had an LDL level above 130 g/dl, 632 above 160 mg/dl and 247 above 175 mg/dl. The Chi square analysis of short stature (height 130 g/dl was also significant (p=0.013) with increased odds of LDL-c above 130 g/dl compared to non-short stature (OR= 1.37, CL 1.07-1.75). Table 1 shows odds ratio for varying levels of elevated LDL-c for the first (shortest) vs. 4th (tallest) quartile of students. Conclusions: Shorter stature is associated with higher LDL-c level in WV 5th graders generally and in those children with increased risk for genetic dyslipidemia. The trend to increasing odds ratio in strata of higher LDL-c supports a recent report of association of single nucleotide polymorphisms selecting for lower genetic height and higher LDL-c.

scholarly journals Genetically Determined Physical Activity and Its Association with Circulating Blood Cells

Genes ◽  
2019 ◽  
Vol 10 (11) ◽  
pp. 908 ◽  
Author(s):  
Femke M. Prins ◽  
M. Abdullah Said ◽  
Yordi J. van de Vegte ◽  
Niek Verweij ◽  
Hilde E. Groot ◽  
...  
Keyword(s):  
Physical Activity ◽  
Blood Cells ◽  
Fixed Effects ◽  
Mendelian Randomization ◽  
P Value ◽  
Nucleotide Polymorphisms ◽  
Increased Risk ◽  
Inflammatory State ◽  
The Uk ◽  
Genetically Determined

Lower levels of physical activity (PA) have been associated with increased risk of cardiovascular disease. Worldwide, there is a shift towards a lifestyle with less PA, posing a serious threat to public health. One of the suggested mechanisms behind the association between PA and disease development is through systemic inflammation, in which circulating blood cells play a pivotal role. In this study we investigated the relationship between genetically determined PA and circulating blood cells. We used 68 single nucleotide polymorphisms associated with objectively measured PA levels to perform a Mendelian randomization analysis on circulating blood cells in 222,645 participants of the UK Biobank. For inverse variance fixed effects Mendelian randomization analyses, p < 1.85 × 10−3 (Bonferroni-adjusted p-value of 0.05/27 tests) was considered statistically significant. Genetically determined increased PA was associated with decreased lymphocytes (β = –0.03, SE = 0.008, p = 1.35 × 10−3) and decreased eosinophils (β = –0.008, SE = 0.002, p = 1.36 × 10−3). Although further mechanistic studies are warranted, these findings suggest increased physical activity is associated with an improved inflammatory state with fewer lymphocytes and eosinophils.

scholarly journals A multivariable Mendelian randomization analysis investigating smoking and alcohol consumption in oral and oropharyngeal cancer

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Mark Gormley ◽  
Tom Dudding ◽  
Eleanor Sanderson ◽  
Richard M. Martin ◽  
Steven Thomas ◽  
...  
Keyword(s):  
Standard Deviation ◽  
Alcohol Consumption ◽  
Oropharyngeal Cancer ◽  
Genome Wide Association Study ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
Strong Association ◽  
Smoking Behaviour ◽  
Standard Deviation Increase ◽  
Independent Effects

AbstractThe independent effects of smoking and alcohol in head and neck cancer are not clear, given the strong association between these risk factors. Their apparent synergistic effect reported in previous observational studies may also underestimate independent effects. Here we report multivariable Mendelian randomization performed in a two-sample approach using summary data on 6,034 oral/oropharyngeal cases and 6,585 controls from a recent genome-wide association study. Our results demonstrate strong evidence for an independent causal effect of smoking on oral/oropharyngeal cancer (IVW OR 2.6, 95% CI = 1.7, 3.9 per standard deviation increase in lifetime smoking behaviour) and an independent causal effect of alcohol consumption when controlling for smoking (IVW OR 2.1, 95% CI = 1.1, 3.8 per standard deviation increase in drinks consumed per week). This suggests the possibility that the causal effect of alcohol may have been underestimated. However, the extent to which alcohol is modified by smoking requires further investigation.

scholarly journals Mineral Nutrition and the Risk of Chronic Diseases: A Mendelian Randomization Study

Nutrients ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 378 ◽  
Author(s):  
Wen-Wen Cheng ◽  
Qiang Zhu ◽  
Hong-Yu Zhang
Keyword(s):  
Chronic Diseases ◽  
Mendelian Randomization ◽  
Fold Increase ◽  
Nucleotide Polymorphisms ◽  
Major Depressive ◽  
Standard Deviation Increase ◽  
Single Nucleotide ◽  
Unit Increase ◽  
Calcium Magnesium

We applied Mendelian randomization analyses to investigate the potential causality between blood minerals (calcium, magnesium, iron, copper, and zinc) and osteoporosis (OP), gout, rheumatoid arthritis (RA), type 2 diabetes (T2D), Alzheimer's disease (AD), bipolar disorder (BD), schizophrenia , Parkinson’s disease and major depressive disorder. Single nucleotide polymorphisms (SNPs) that are independent (r2 < 0.01) and are strongly related to minerals (p < 5 × 10−8) are selected as instrumental variables. Each standard deviation increase in magnesium (0.16 mmol/L) is associated with an 8.94-fold increase in the risk of RA (p = 0.044) and an 8.78-fold increase in BD (p = 0.040) but a 0.10 g/cm2 increase in bone density related to OP (p = 0.014). Each per-unit increase in copper is associated with a 0.87-fold increase in the risk of AD (p = 0.050) and BD (p = 0.010). In addition, there is suggestive evidence that calcium is positively correlated (OR = 1.36, p = 0.030) and iron is negatively correlated with T2D risk (OR = 0.89, p = 0.010); both magnesium (OR = 0.26, p = 0.013) and iron (OR = 0.71, p = 0.047) are negatively correlated with gout risk. In the sensitivity analysis, causal estimation is not affected by pleiotropy. This study supports the long-standing hypothesis that magnesium supplementation can increase RA and BD risks and decrease OP risk and that copper intake can reduce AD and BD risks. This study will be helpful to address some controversial debates on the relationships between minerals and chronic diseases.

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