scholarly journals Modifiable risk factors for epilepsy: A two‐sample Mendelian randomization study

2021 ◽  
Author(s):  
Shuai Yuan ◽  
Torbjörn Tomson ◽  
Susanna C. Larsson
Keyword(s):  
Risk Factors ◽  
Mendelian Randomization ◽  
Modifiable Risk Factors

scholarly journals Modifiable Risk Factors for Incident Dementia and Cognitive Impairment: An Umbrella Review of Evidence

2021 ◽  
Author(s):  
Yaru Zhang ◽  
Wei Xu ◽  
Wei Zhang ◽  
Hui-Fu Wang ◽  
Ya-Nan Ou ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cognitive Impairment ◽  
Systematic Reviews ◽  
Plasma Glucose ◽  
Prospective Studies ◽  
Mendelian Randomization ◽  
Convincing Evidence ◽  
Modifiable Risk Factors ◽  
Umbrella Review ◽  
Modifiable Factors

Abstract Dementia and cognitive impairment can be attributed to both genetic and modifiable risk factors. Recently, considerable evidence emerged and urgently require standardized evaluation. To address it, we conducted an umbrella review of prospective studies regarding the associations of dementia and cognitive impairment with modifiable factors to evaluate the strength and validity of the existing evidence. We searched PubMed, Embase, CINAHL and Cochrane Database of Systematic Reviews to identify relevant systematic reviews and meta-analyses of prospective studies. Mendelian randomization studies were reviewed to assess the causality for these associations. For each association, we analyzed the summary effect size, 95% confidence interval, 95% prediction interval, heterogeneity, small study effect and excess significance bias. Based on these estimates, the evidence was graded into levels of convincing, highly suggestive, suggestive, or weak. In total, 12015 articles were identified, of which 118 eligible studies yielded 243 unique associations. Convincing evidence was found for associations of dementia and cognitive impairment with early-life education, midlife to late-life plasma glucose, body mass index, atrial fibrillation, benzodiazepine use, and gait speed. Suggestive to highly suggestive evidence was found for associations of dementia and cognitive impairment with midlife to late-life blood pressure, homocysteine, cerebrovascular diseases, hearing impairment, respiratory illness, anemia, smoking, alcohol consumption, diet, sleep, physical activity and social engagement. Among convincing evidence, Mendelian randomization studies verified genetic predicted causal relationships for education and plasma glucose with Alzheimer's disease. Modifiable factors identified in this study, especially those with high-level evidence, should be considered in dementia prevention. Trial registration: PROSPERO CRD42020195729.

scholarly journals Evaluating causal associations between previously reported risk factors and epithelial ovarian cancer: a Mendelian randomization analysis

2018 ◽  
Author(s):  
James Yarmolinsky ◽  
Caroline L Relton ◽  
Artitaya Lophatananon ◽  
Kenneth Muir ◽  
Usha Menon ◽  
...  
Keyword(s):  
Risk Factors ◽  
Ovarian Cancer ◽  
Cancer Risk ◽  
Epithelial Ovarian Cancer ◽  
Genetic Variants ◽  
Mendelian Randomization ◽  
Modifiable Risk Factors ◽  
Ovarian Cancer Risk ◽  
Genetic Liability ◽  
Suggestive Evidence

AbstractBackgroundVarious modifiable risk factors have been associated with epithelial ovarian cancer risk in observational epidemiological studies. However, the causal nature of the risk factors reported, and thus their suitability as effective intervention targets, is unclear given the susceptibility of conventional observational designs to residual confounding and reverse causation. Mendelian randomization uses genetic variants as proxies for modifiable risk factors to strengthen causal inference in observational studies. We used Mendelian randomization to evaluate the causal role of 13 previously reported risk factors (reproductive, anthropometric, clinical, lifestyle, and molecular factors) in overall and histotype-specific epithelial ovarian cancer in up to 25,509 case subjects and 40,941 controls in the Ovarian Cancer Association Consortium.Methods and FindingsGenetic instruments to proxy 13 risk factors were constructed by identifying single nucleotide polymorphisms (SNPs) robustly (P<5×10−8) and independently associated with each respective risk factor in previously reported genome-wide association studies. SNPs were combined into multi-allelic inverse-variance weighted fixed or random-effects models to generate causal estimates. Three complementary sensitivity analyses were performed to examine violations of Mendelian randomization assumptions: MR-Egger regression and weighted median and mode estimators. A Bonferroni-corrected P-value threshold was used to establish “strong evidence” (P<0.0038) and “suggestive evidence” (0.0038<P<0.05) for associations.In Mendelian randomization analyses, there was strong or suggestive evidence that 9 of 13 risk factors had a causal effect on overall or histotype-specific epithelial ovarian cancer. There was strong evidence that genetic liability to endometriosis increased risk of epithelial ovarian cancer (OR per log odds higher liability:1.27, 95% CI: 1.16-1.40; P=6.94×10−7) and suggestive evidence that lifetime smoking exposure increased risk of epithelial ovarian cancer (OR per unit increase in smoking score:1.36, 95% CI: 1.04-1.78; P=0.02). In histotype-stratified analyses, the strongest associations found were between: height and clear cell carcinoma (OR per SD increase:1.36, 95% CI: 1.15-1.61; P=0.0003); age at natural menopause and endometrioid carcinoma (OR per year later onset:1.09, 95% CI: 1.02-1.16; P=0.007); and genetic liability to polycystic ovary syndrome and endometrioid carcinoma (OR per log odds higher liability:0.74, 95% CI:0.62-0.90; P=0.002). There was little evidence for an effect of genetic liability to type 2 diabetes, parity, or circulating levels of 25-hydroxyvitamin D and sex hormone-binding globulin on ovarian cancer or its subtypes. The primary limitations of this analysis include: modest statistical power for analyses of risk factors in relation to some less common ovarian cancer histotypes (low grade serous, mucinous, and clear cell carcinomas), the inability to directly examine the causal effects of some ovarian cancer risk factors that did not have robust genetic variants available to serve as proxies (e.g., oral contraceptives, hormone replacement therapy), and the assumption of linear relationships between risk factors and ovarian cancer risk.ConclusionsOur comprehensive examination of possible etiological drivers of ovarian carcinogenesis using germline genetic variants to proxy risk factors supports a causal role for few of these factors in epithelial ovarian cancer and suggests distinct etiologies across histotypes. The identification of novel modifiable risk factors remains an important priority for the control of epithelial ovarian cancer.

scholarly journals Novel insights into modifiable risk factors of cholelithiasis: A Mendelian randomization study

Hepatology ◽  
2021 ◽  
Author(s):  
Lanlan Chen ◽  
Hongqun Yang ◽  
Haitao Li ◽  
Chang He ◽  
Liu Yang ◽  
...  
Keyword(s):  
Risk Factors ◽  
Mendelian Randomization ◽  
Modifiable Risk Factors

scholarly journals Associations between Potentially Modifiable Risk Factors and Alzheimer Disease: A Mendelian Randomization Study

PLoS Medicine ◽  
2015 ◽  
Vol 12 (6) ◽  
pp. e1001841 ◽  
Author(s):  
Søren D. Østergaard ◽  
Shubhabrata Mukherjee ◽  
Stephen J. Sharp ◽  
Petroula Proitsi ◽  
Luca A. Lotta ◽  
...  
Keyword(s):  
Risk Factors ◽  
Alzheimer Disease ◽  
Mendelian Randomization ◽  
Modifiable Risk Factors

scholarly journals A modifiable risk factors atlas of lung cancer: A Mendelian randomization study

2021 ◽  
Author(s):  
Jiayi Shen ◽  
Huaqiang Zhou ◽  
Jiaqing Liu ◽  
Yaxiong Zhang ◽  
Ting Zhou ◽  
...  
Keyword(s):  
Risk Factors ◽  
Lung Cancer ◽  
Mendelian Randomization ◽  
Modifiable Risk Factors

scholarly journals Modifiable Risk Factors for Intracranial Aneurysm and Aneurysmal Subarachnoid Hemorrhage: A Mendelian Randomization Study

2021 ◽  
Author(s):  
Ville Karhunen ◽  
Mark K. Bakker ◽  
Ynte M. Ruigrok ◽  
Dipender Gill ◽  
Susanna C. Larsson
Keyword(s):  
Physical Activity ◽  
Risk Factors ◽  
Blood Pressure ◽  
Body Mass Index ◽  
Subarachnoid Hemorrhage ◽  
Intracranial Aneurysm ◽  
Mendelian Randomization ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Sensitivity Analyses ◽  
Modifiable Risk Factors

Background The aim of this study was to assess the associations of modifiable lifestyle factors (smoking, coffee consumption, sleep, and physical activity) and cardiometabolic factors (body mass index, glycemic traits, type 2 diabetes, systolic and diastolic blood pressure, lipids, and inflammation and kidney function markers) with risks of any (ruptured or unruptured) intracranial aneurysm and aneurysmal subarachnoid hemorrhage using Mendelian randomization. Methods and Results Summary statistical data for the genetic associations with the modifiable risk factors and the outcomes were obtained from meta‐analyses of genome‐wide association studies. The inverse‐variance weighted method was used as the main Mendelian randomization analysis, with additional sensitivity analyses conducted using methods more robust to horizontal pleiotropy. Genetic predisposition to smoking, insomnia, and higher blood pressure was associated with an increased risk of both intracranial aneurysm and aneurysmal subarachnoid hemorrhage. For intracranial aneurysm, the odds ratios were 3.20 (95% CI, 1.93–5.29) per SD increase in smoking index, 1.24 (95% CI, 1.10–1.40) per unit increase in log‐odds of insomnia, and 2.92 (95% CI, 2.49–3.43) per 10 mm Hg increase in diastolic blood pressure. In addition, there was weak evidence for associations of genetically predicted decreased physical activity, higher triglyceride levels, higher body mass index, and lower low‐density lipoprotein cholesterol levels with higher risk of intracranial aneurysm and aneurysmal subarachnoid hemorrhage, with 95% CI overlapping the null for at least 1 of the outcomes. All results were consistent in sensitivity analyses. Conclusions This Mendelian randomization study suggests that smoking, insomnia, and high blood pressure are major risk factors for intracranial aneurysm and aneurysmal subarachnoid hemorrhage.

scholarly journals Identifying modifiable risk factors of lung cancer: Indications from Mendelian randomization

PLoS ONE ◽  
2021 ◽  
Vol 16 (10) ◽  
pp. e0258498
Author(s):  
Jie Ding ◽  
Zhenxing Tu ◽  
Hongquan Chen ◽  
Zhiguang Liu
Keyword(s):  
Risk Factors ◽  
Lung Cancer ◽  
Causal Relationship ◽  
Mendelian Randomization ◽  
Smoking Behavior ◽  
Hdl Cholesterol ◽  
P Value ◽  
Modifiable Risk Factors ◽  
Inverse Variance ◽  
Quitting Smoking

Background Lung cancer is the major cause of mortality in tumor patients. While its incidence rate has recently declined, it is still far from satisfactory and its potential modifiable risk factors should be explored. Methods We performed a two-sample Mendelian randomization (MR) study to investigate the causal relationship between potentially modifiable risk factors (namely smoking behavior, alcohol intake, anthropometric traits, blood pressure, lipidemic traits, glycemic traits, and fasting insulin) and lung cancer. Besides, a bi-directional MR analysis was carried out to disentangle the complex relationship between different risk factors. Inverse-variance weighted (IVW) was utilized to combine the estimation for each SNP. Cochrane’s Q value was used to evaluate heterogeneity and two methods, including MR-Egger intercept and MR-PRESSO, were adopted to detect horizontal pleiotropy. Results Three kinds of smoking behavior were all causally associated with lung cancer. Overall, smokers were more likely to suffer from lung cancer compared with non-smokers (OR = 2.58 [1.95, 3.40], p-value = 2.07 x 10−11), and quitting smoking could reduce the risk (OR = 4.29[2.60, 7.07], p-value = 1.23 x 10−8). Furthermore, we found a dose-response relationship between the number of cigarettes and lung cancer (OR = 6.10 [5.35, 6.96], p-value = 4.43x10-161). Lower HDL cholesterol could marginally increase the risk of lung cancer, but become insignificant after Bonferroni correction (OR = 0.82 [0.68, 1.00], p-value = 0.045). In addition, we noted no direct causal relationship between other risk factors and lung cancer. Neither heterogeneity nor pleiotropy was observed in this study. However, when treating the smoking behavior as the outcome, we found the increased BMI could elevate the number of cigarettes per day (beta = 0.139[0.104, 0.175], p-value = 1.99x10-14) and a similar effect was observed for the waist circumference and hip circumference. Additionally, the elevation of SBP could also marginally increase the number of cigarettes per day (beta = 0.001 [0.0002, 0.002], p-value = 0.018). Conclusion Smoking behavior might be the most direct and effective modifiable way to reduce the risk of lung cancer. Meanwhile, smoking behavior can be affected by other risk factors, especially obesity.

Sign in / Sign up

Export Citation Format

Share Document