scholarly journals GENE-11. LDSCORE REGRESSION IDENTIFIES NOVEL ASSOCIATIONS BETWEEN GLIOMA AND AUTO-IMMUNE CONDITIONS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi99-vi100
Author(s):  
Quinn Ostrom ◽  
Jacob Edelson ◽  
Jinyoung Byun ◽  
Younghun Han ◽  
Kyle Walsh ◽  
...  
Keyword(s):  
Allergic Rhinitis ◽  
Genetic Correlation ◽  
Meta Analysis ◽  
Epidemiological Studies ◽  
Summary Statistics ◽  
Case Control Studies ◽  
Risk Variants ◽  
History Of ◽  
The Uk ◽  
Novel Associations

Abstract BACKGROUND Prior epidemiological studies in glioma have identified 25 germline risk variants, as well as risk associations with exposure to ionizing radiation (which increases risk) and history of allergies and aspirin use (which decrease risk). In this analysis we LDscore regression, which leverages single SNP associations and known patterns of linkage disequilibrium (LD) to estimate the genetic correlation between phenotypes, to confirm prior associations as well as attempt to identify novel phenotype associations for traits not previously assessed that may improve genetic prediction for glioma. METHODS Summary statistics for all glioma, GBM, and non-GBM were obtained from a prior meta-analysis conducted by Melin, et al. Summary statistics for 13 immune- and atopy-related traits were obtained from the prior case-control studies and the UK biobank. Data were filtered to include only SNPs with imputation INFO value >0.7, and minor allele frequency >0.01, excluding SNPs within the HLA region. Pairwise genetic correlation between these traits was generated using LDSC. Associations were considered significant at p< 0.05 RESULTS Significant negative correlations were identified between glioma and ulcerative colitis (rg= -0.4039, p=4.91x10-10), celiac disease (rg= -0.2028, p=1.18x10-4), lupus (rg= -0.0956, p=0.0083), and multiple sclerosis (rg= -0.5755, p=4.46x10-9). These associations were generally consistent in both GBM and non-GBM. There was a significant correlation between both self-reported (rg= -0.102, p=0.0233) and doctor diagnosed (rg= -0.116, p=0.0305) hayfever/allergic rhinitis and GBM only. CONCLUSIONS This analysis demonstrates a genetic basis for previously identified protective effect of allergic rhinitis on GBM, and identifies novel associations between multiple auto-immune traits and glioma. Further studies are necessary in order to confirm these associations and identify the mechanism through which increased immune activity may lower risk of glioma.

Inverse Relationship Between Serum Bilirubin and Atherosclerosis in Men: A Meta-Analysis of Published Studies

2003 ◽  
Vol 228 (5) ◽  
pp. 568-571 ◽  
Author(s):  
Ladislav Novotný ◽  
Libor Vítek
Keyword(s):  
Inverse Relationship ◽  
Serum Bilirubin ◽  
Linear Trend ◽  
Meta Analysis ◽  
Negative Relationship ◽  
Epidemiological Studies ◽  
Atherosclerotic Disease ◽  
Categorical Variables ◽  
History Of ◽  
Stratified Analysis

Bilirubin, a major intravascular product of heme catabolism, is a potent antioxidant compound. Numerous studies have been published showing the relationship between serum bilirubin levels and atherosclerosis. In the present investigation all the epidemiological studies available on the effect of serum bilirubin levels and atherosclerotic disease were analyzed. Studies on the epidemiology of atherosclerotic diseases in relation to serum bilirubin levels were searched in the MEDLINE database. Selected studies were subdivided according to serum bilirubin levels and severity of atherosclerotic disease. Because of the limited number of females involved in the studies, only males were included into meta-analysis. Associations for ordered categorical variables (bilirubin and natural history of graded atherosclerosis) were assessed to find correlation and linear trend between analyzed variables. A stratified analysis was conducted to compare risks of clinical outcomes. Eleven relevant studies were used for analysis. A close negative relationship was found between serum bilirubin levels and severity of atherosclerosis (Spearman rank coefficient r = −0.31, P < 0.0001). The linear trend was confirmed in analysis of proportions with x2 values for both disease conditions to be very significant ( P < 0.0001). Unambiguous inverse relationship between serum bilirubin levels and atherosclerosis was demonstrated in this preliminary meta-analytic study. These results indicate the importance of hem oxygenase-related products in the prevention of oxidative stress-mediated diseases.

Phenotypic and Genotypic Associations Between Migraine and Lipoprotein Subtractions

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000012919
Author(s):  
Yanjun Guo ◽  
Iyas Daghlas ◽  
Padhraig Gormley ◽  
Franco Giulianini ◽  
Paul M Ridker ◽  
...  
Keyword(s):  
Genetic Correlation ◽  
Genetic Relationships ◽  
Meta Analysis ◽  
European Ancestry ◽  
Health Study ◽  
Lipoprotein Subfractions ◽  
Genetic Components ◽  
The Uk ◽  
Summary Data

Background and Objective:To evaluate phenotypic and genetic relationships between migraine and lipoprotein subfractions.Methods:We evaluated phenotypic associations between migraine and 19 lipoprotein subfractions measures in the Women’s Genome Health Study (WGHS, N=22,788). We then investigated genetic relationships between these traits using summary statistics from the International Headache Genetics Consortium (IHGC) for migraine (Ncase=54,552, Ncontrol=297,970) and combined summary data for lipoprotein subfractions (N up to 47,713).Results:There was a significant phenotypic association (odds ratio=1.27 [95% confidence interval:1.12-1.44]) and a significant genetic correlation at 0.18 (P=0.001) between migraine and triglyceride-rich lipoproteins (TRLP) concentration but not for LDL or HDL subfractions. Mendelian randomization (MR) estimates were largely null implying that pleiotropy rather than causality underlies the genetic correlation between migraine and lipoprotein subfractions. Pleiotropy was further supported in cross-trait meta-analysis revealing significant shared signals at four loci (chr2p21 harboring THADA, chr5q13.3 harboring HMGCR, chr6q22.31 harboring HEY2, and chr7q11.23 harboring MLXIPL) between migraine and lipoprotein subfractions. Three of these loci were replicated for migraine (P<0.05) in a smaller sample from the UK Biobank. The shared signal at chr5q13.3 colocalized with expression of HMGCR, ANKDD1B, and COL4A3BP in multiple tissues.Conclusions:The current study supports the association between certain lipoprotein subfractions, especially for TRLP, and migraine in populations of European ancestry. The corresponding shared genetic components may be help identify potential targets for future migraine therapeutics.Classification of Evidence:This study provides Class I evidence that migraine is significantly associated with some lipoprotein subfractions.

scholarly journals Dietary patterns and CVD: a systematic review and meta-analysis of observational studies

2015 ◽  
Vol 114 (9) ◽  
pp. 1341-1359 ◽  
Author(s):  
Míriam Rodríguez-Monforte ◽  
Gemma Flores-Mateo ◽  
Emília Sánchez
Keyword(s):  
Cohort Studies ◽  
Dietary Patterns ◽  
Observational Studies ◽  
Protective Factor ◽  
Meta Analysis ◽  
Epidemiological Studies ◽  
Case Control ◽  
Case Control Studies ◽  
Chd Risk ◽  
Control Comparison

AbstractEpidemiological studies show that diet is linked to the risk of developing CVD. The objective of this meta-analysis was to estimate the association between empirically derived dietary patterns and CVD. PubMed was searched for observational studies of data-driven dietary patterns that reported outcomes of cardiovascular events. The association between dietary patterns and CVD was estimated using a random-effects meta-analysis with 95 % CI. Totally, twenty-two observational studies met the inclusion criteria. The pooled relative risk (RR) for CVD, CHD and stroke in a comparison of the highest to the lowest category of prudent/healthy dietary patterns in cohort studies was 0·69 (95 % CI 0·60, 0·78; I2=0 %), 0·83 (95 % CI 0·75, 0·92; I2=44·6 %) and 0·86 (95 % CI 0·74, 1·01; I2=59·5 %), respectively. The pooled RR of CHD in a case–control comparison of the highest to the lowest category of prudent/healthy dietary patterns was 0·71 (95 % CI 0·63, 0·80; I2=0 %). The pooled RR for CVD, CHD and stroke in a comparison of the highest to the lowest category of western dietary patterns in cohort studies was 1·14 (95 % CI 0·92, 1·42; I2=56·9 %), 1·03 (95 % CI 0·90, 1·17; I2=59·4 %) and 1·05 (95 % CI 0·91, 1·22; I2=27·6 %), respectively; in case–control studies, there was evidence of increased CHD risk. Our results support the evidence of the prudent/healthy pattern as a protective factor for CVD.

Abstract P147: Genome Wide Assessment of Shared Genetic Architecture Between Rheumatoid Arthritis and Cardiovascular Diseases Using the UK Biobank Data

Circulation ◽  
2020 ◽  
Vol 141 (Suppl_1) ◽  
Author(s):  
Yanjun Guo ◽  
Wonil Chung ◽  
Zhilei Shan ◽  
Liming Liang
Keyword(s):  
Cardiovascular Diseases ◽  
Genetic Correlation ◽  
Multiple Testing ◽  
Mendelian Randomization ◽  
Meta Analysis ◽  
Uk Biobank ◽  
Increased Risk ◽  
The Uk ◽  
Cardiovascular Traits ◽  
Shared Genetic

Background: Patients with RA have a 2-10 folds increased risk of cardiovascular diseases (CVD) and CVD accounts for almost 50% of the excess mortality in patients with RA when compared with general population, but the mechanisms underlying such associations are largely unknown. Methods: We examined the genetic correlation, causality, and shared genetic variants between RA (Ncase=6,756, Ncontrol=452,476) and CVD (Ncase=44,246, Ncontrol=414,986) using LD Score regression (LDSC), generalized summary-data-based Mendelian Randomization (GSMR), and cross-trait meta-analysis in the UK Biobank Data. Results: In the present study, RA was significantly genetically correlated with MI, angina, CHD, and CVD after correcting for multiple testing (Rg ranges from 0.40 to 0.43, P<0.05/5). Interestingly, when stratified by frequent usage of aspirin and paracetamol, we observed increased genetic correlation between RA and CVD for participants without aspirin usage ( Rg increased to 0.54 [95%CI: 0.54, 0.78] for angina; P value=6.69х10 -6 ), and for participants with usage of paracetamol ( Rg increased to 0.75 [95%CI: 0.20, 1.29] for MI; P value=8.90х10 -3 ). Cross-trait meta-analysis identified 9 independent loci that were shared between RA and at least one of the genetically correlated CVD traits including PTPN22 at chr1p13.2 , BCL2L11 at chr2q13 , and CCR3 at chr3p21.31 ( P single trait <1х10 -3 and P meta <5х10 -8 ) highlighting potential shared etiology between them which include accelerating atherosclerosis and upregulating oxidative stress and vascular permeability. Finally, Mendelian randomization analyses observed inconsistent instrumental effects and were unable to conclude the causality and directionality between RA and CVD. Conclusion: Our results supported positive genetic correlation between RA and multiple cardiovascular traits, and frequent usage of aspirin and paracetamol may modify their associations, but instrumental analyses were unable to conclude the causality and directionality between them.

Effect of Exposure to Cats and Dogs on the Risk of Asthma and Allergic Rhinitis: A Systematic Review and Meta-analysis

2020 ◽  
Vol 34 (5) ◽  
pp. 703-714
Author(s):  
Xiaoping Gao ◽  
Mei Yin ◽  
Pei Yang ◽  
Xia Li ◽  
Lingling Di ◽  
...  
Keyword(s):  
Systematic Review ◽  
Allergic Rhinitis ◽  
Cohort Studies ◽  
Meta Analysis ◽  
Pooled Analysis ◽  
Protective Role ◽  
Case Control ◽  
Favorable Effect ◽  
Case Control Studies

Background Controversies persist regarding whether exposure to cat or dog increases the risk of asthma and allergic rhinitis. Objective This meta-analysis aimed to assess the associations between exposure to cats or dogs and the development of asthma and allergic rhinitis. Methods A systematic review was performed to identify case-control and cohort studies before May 2019, evaluating the association between exposure to cats and dogs and the risk of asthma and rhinitis. The risk of bias was assessed using the Newcastle–Ottawa Scale. The odds ratios (ORs) and risk ratios (RRs) were pooled for case-control and cohort studies, respectively. Subgroup analyses were performed on prespecified study-level characteristics. Results The meta-analysis of 34 cohort studies showed a protective role of exposure to cats [RR: 0.88, 95% confidence interval (CI): 0.77–0.99] or dogs (RR: 0.85, 95% CI: 0.73–0.97) in the development of asthma. The subgroup analysis of birth cohort (RR: 0.74, 95% CI: 0.56–0.93) and children population (RR: 0.83, 95% CI: 0.70–0.96) also suggested a favorable role of exposure to dogs in the development of asthma. Pooled evidence from 13 case-control studies indicated no significant impact of cats (OR: 1.66, 95% CI: 0.39–2.94) and dogs (OR: 1.22, 95% CI: 0.92–1.52) on the development of asthma. A pooled analysis of five cohort studies showed a favorable effect of exposure to cats (RR: 0.60, 95% CI: 0.33–0.86) or dogs (RR: 0.68, 95% CI 0.44–0.90) on the development of allergic rhinitis. Conclusion The findings indicated a protective effect of exposure to cats and dogs, especially ownership, on the development of asthma and allergic rhinitis.

scholarly journals History of allergic rhinitis and risk of asthma; a systematic review and meta-analysis

2019 ◽  
Vol 12 (10) ◽  
pp. 100069 ◽  
Author(s):  
Hamid Reza Tohidinik ◽  
Narmeen Mallah ◽  
Bahi Takkouche
Keyword(s):  
Systematic Review ◽  
Allergic Rhinitis ◽  
Meta Analysis ◽  
History Of

scholarly journals Shift Work and Prostate Cancer: An Updated Systematic Review and Meta-Analysis

2020 ◽  
Vol 17 (4) ◽  
pp. 1345 ◽  
Author(s):  
Mario Rivera-Izquierdo ◽  
Virginia Martínez-Ruiz ◽  
Elena Mercedes Castillo-Ruiz ◽  
Miriam Manzaneda-Navío ◽  
Beatriz Pérez-Gómez ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Publication Bias ◽  
Shift Work ◽  
Meta Analysis ◽  
Night Shift ◽  
Epidemiological Studies ◽  
Potential Effect ◽  
Current Data ◽  
International Agency ◽  
Case Control Studies

The International Agency of Research in Cancer (IARC) has recently confirmed shift work as a type 2A carcinogen. The results presented in published epidemiological studies regarding prostate cancer are inconsistent and the association remains controversial. The aims of this study were: (a) to investigate the possible association between shift work and prostate cancer incidence, identifying possible sources of heterogeneity; and (b) to analyze the potential effect of publication bias. A search for cohort and case-control studies published from January 1980 to November 2019 was conducted. The quality of the articles was assessed using the Newcastle–Ottawa Scale. Pooled OR were calculated using random-effects models. Heterogeneity was evaluated using Cochran’s Q test and data were stratified by potential sources of heterogeneity. Publication bias was analyzed. Eighteen studies were included. No association was found between rotating/night-shift work and prostate cancer, pooled OR 1.07 (95%CI 0.99 to 1.15), I2 = 45.7%, p = 0.016. Heterogeneity was eliminated when only cohort studies (pooled OR 1.03; 95%CI 0.96 to 1.10; I2 = 18.9%, p = 0.264) or high-quality studies (pooled OR 0.99; 95%CI 0.89 to 1.08; I2 = 0.0%, p = 0.571) were considered. A publication bias was detected. An association between shift work and prostate cancer cannot be confirmed with the available current data. Future analytical studies assessing more objective homogeneous exposure variables still seem necessary.

scholarly journals P.1.36 Occupational cohort studies: safeguarding a valuable resource

2019 ◽  
Vol 76 (Suppl 1) ◽  
pp. A86.2-A86
Author(s):  
Katherine Venables ◽  
Nicola Fear ◽  
Lucy Carpenter ◽  
Thomas Keegan ◽  
Claire Brooks ◽  
...  
Keyword(s):  
Cohort Studies ◽  
Data Access ◽  
Epidemiological Studies ◽  
Case Control Studies ◽  
Strategic Review ◽  
Pharmacological Studies ◽  
Occupational Cohort ◽  
Set Up ◽  
The Uk ◽  
Nested Case Control

An occupational cohort study is the most robust epidemiological design for studying the effects of workplace hazards and the findings can be extended to the general environment. A cohort may be time-consuming, expensive, and labour-intensive to set up but, once done, it can be extended forward in time, as well as laterally to incorporate new outcome variables, and it can also support nested case-control studies. It is therefore important that the human and material investment is preserved so that these valuable resources can be fully exploited.In recent years, the bureaucratic burden on researchers in many countries has increased. In the UK, for example, research ethics, data protection, and data access application procedures have become more cumbersome, with an increase in the number of supporting documents required from researchers. Although fast-track procedures exist, epidemiological studies often require the same formal procedures and oversights as more invasive and potentially dangerous physiological and pharmacological studies.Fortunately, there are now initiatives which support occupational cohort studies. The UK Medical Research Council (MRC), for example, published in 2014 a review and guidance about maximising the value of UK population cohorts and it has also set up a Cohort Strategic Review Group to pre-assess funding applications for new cohorts and for updates to existing cohorts (http://mrc.ukri.org). As another example, OMEGA-NET has been set up to ‘create a network to optimize and integrate occupational, industrial, and population cohorts at the European level’ (http://omeganetcohorts.eu/).We propose that a checklist be defined for assessment of research protocols for new cohorts or updates to existing cohorts, in order to assist official committees in their work and streamline the approval process for both researchers and committees. EPICOH would be well-placed to draft and promulgate such a checklist, working with interested organisations, such as OMEGA-NET and the UK MRC.

Colorectal cancer and hormone replacement therapy: a review of epidemiological studies

2000 ◽  
Vol 6 (1) ◽  
pp. 8-14 ◽  
Author(s):  
Esteve Fernandez ◽  
Silvia Franceschi ◽  
Carlo La Vecchia
Keyword(s):  
Colorectal Cancer ◽  
Meta Analysis ◽  
Hormone Replacement ◽  
Significant Risk ◽  
Developed Countries ◽  
Epidemiological Studies ◽  
Inverse Association ◽  
Case Control Studies ◽  
Relative Risks ◽  
Increased Risk

Mortality rates for colorectal cancer in many developed countries have declined in women more than in men. Possible explanations of the sex differentials in colorectal cancer mainly, but not only, refer to different exposure to exogenous hormones. This paper aims to review the available epidemiological evidence on this issue. Seven cohort studies reported information on HRT use and colorectal cancer risk, with relative risks (RRs) around or below unity, and significant inverse association was found in two of them. Of 12 case-control studies, five reported significant risk reductions among ever-users of HRT, while two investigations showed moderate, non-significant inverse associations and none showed a significant increased risk. Two recent meta-analysis showed a 20% reduction in the risk of colon cancer among current users. Overall, the studies reviewed support the existence of an inverse association between colorectal cancer and HRT. Although these epidemiological observations are consistent, surveillance bias may account for part of the association.

Radon: Occupational or Domestic Carcinogen?

1994 ◽  
Vol 56 (1-4) ◽  
pp. 81-88 ◽  
Author(s):  
G. Monchaux ◽  
R. Masse (INVITED)
Keyword(s):  
Lung Cancer ◽  
Indoor Radon ◽  
Meta Analysis ◽  
Epidemiological Studies ◽  
Biological Data ◽  
Excess Risk ◽  
Underground Mines ◽  
Case Control Studies ◽  
Remedial Actions ◽  
Radon Measurements

Abstract An association between an excess risk of lung cancer and exposure to radon and its daughters has been demonstrated in uranium miners and in other miners. In various countries, radon measurements in dwellings showed that indoor radon concentrations are in the same range as in underground mines. Geographical epidemiological studies do not show an excess risk of lung cancer in people living in radon rich areas and case-control studies of domestic exposures lead to conflicting results. A joint study allowing meta-analysis of the results from 19 epidemiological studies carried out throughout the world should provide reliable data by and after 1995. Experimental data and biological data from radon-induced human tumours might allow the identification of tumours induced by irradiation compared with tumours induced by other agents. Until now, the role of domestic exposure in the occurrence of lung cancer remains unclear and therefore the usefulness of remedial actions questionable.

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