scholarly journals Relationship between obesity and the risk of clinically significant depression: Mendelian randomisation study

2014 ◽  
Vol 205 (1) ◽  
pp. 24-28 ◽  
Author(s):  
Chi-Fa Hung ◽  
Margarita Rivera ◽  
Nick Craddock ◽  
Michael J. Owen ◽  
Michael Gill ◽  
...  
Keyword(s):  
Major Depression ◽  
Causal Relationship ◽  
Instrumental Variable ◽  
Common Mental Disorders ◽  
Genetic Risk Score ◽  
Linear Regression Analysis ◽  
Mendelian Randomisation ◽  
Probit Regression ◽  
Reverse Causality ◽  
Increased Risk

BackgroundObesity has been shown to be associated with depression and it has been suggested that higher body mass index (BMI) increases the risk of depression and other common mental disorders. However, the causal relationship remains unclear and Mendelian randomisation, a form of instrumental variable analysis, has recently been employed to attempt to resolve this issue.AimsTo investigate whether higher BMI increases the risk of major depression.MethodTwo instrumental variable analyses were conducted to test the causal relationship between obesity and major depression in RADIANT, a large case–control study of major depression. We used a single nucleotide polymorphism (SNP) in FTO and a genetic risk score (GRS) based on 32 SNPs with well-established associations with BMI.ResultsLinear regression analysis, as expected, showed that individuals carrying more risk alleles of FTO or having higher score of GRS had a higher BMI. Probit regression suggested that higher BMI is associated with increased risk of major depression. However, our two instrumental variable analyses did not support a causal relationship between higher BMI and major depression (FTO genotype: coefficient −0.03, 95% CI −0.18 to 0.13, P = 0.73; GRS: coefficient −0.02, 95% CI −0.11 to 0.07, P = 0.62).ConclusionsOur instrumental variable analyses did not support a causal relationship between higher BMI and major depression. The positive associations of higher BMI with major depression in probit regression analyses might be explained by reverse causality and/or residual confounding.

scholarly journals Examining the possible causal relationship between lung function, COPD and Alzheimer’s disease: a Mendelian randomisation study

2021 ◽  
Vol 8 (1) ◽  
pp. e000759
Author(s):  
Daniel Higbee ◽  
Raquel Granell ◽  
Esther Walton ◽  
Roxanna Korologou-Linden ◽  
George Davey Smith ◽  
...  
Keyword(s):  
Risk Factors ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Lung Function ◽  
Causal Relationship ◽  
Mendelian Randomisation ◽  
P Value ◽  
Unmeasured Confounding ◽  
Increased Risk ◽  
Shared Risk

RationaleLarge retrospective case-control studies have reported an association between chronic obstructive pulmonary disease (COPD), reduced lung function and an increased risk of Alzheimer’s disease. However, it remains unclear if these diseases are causally linked, or due to shared risk factors. Conventional observational epidemiology suffers from unmeasured confounding and reverse causation. Additional analyses addressing causality are required.ObjectivesTo examine a causal relationship between COPD, lung function and Alzheimer’s disease.MethodsUsing two-sample Mendelian randomisation, we used single nucleotide polymorphisms (SNPs) identified in a genome wide association study (GWAS) for lung function as instrumental variables (exposure). Additionally, we used SNPs discovered in a GWAS for COPD in those with moderate to very severe obstruction. The effect of these SNPs on Alzheimer’s disease (outcome) was taken from a GWAS based on a sample of 24 807 patients and 55 058 controls.ResultsWe found minimal evidence for an effect of either lung function (OR: 1.02 per SD; 95% CI 0.91 to 1.13; p value 0.68) or liability for COPD on Alzheimer’s disease (OR: 0.97 per SD; 95% CI 0.92 to 1.03; p value 0.40).ConclusionNeither reduced lung function nor liability COPD are likely to be causally associated with an increased risk of Alzheimer’s, any observed association is likely due to unmeasured confounding. Scientific attention and health prevention policy may be better focused on overlapping risk factors, rather than attempts to reduce risk of Alzheimer’s disease by targeting impaired lung function or COPD directly.

scholarly journals Sleep Disordered Breathing, Obesity and Atrial Fibrillation: A Mendelian Randomisation Study

Genes ◽  
2022 ◽  
Vol 13 (1) ◽  
pp. 104
Author(s):  
Maddalena Ardissino ◽  
Rohin K. Reddy ◽  
Eric A. W. Slob ◽  
Kiran H. K. Patel ◽  
David K. Ryan ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Sleep Disordered Breathing ◽  
Sensitivity Analyses ◽  
Mendelian Randomisation ◽  
Nucleotide Polymorphisms ◽  
Reverse Causality ◽  
Primary Analysis ◽  
Obstructive Sleep ◽  
Increased Risk ◽  
Disordered Breathing

It remains unclear whether the association between obstructive sleep apnoea (OSA), a form of sleep-disordered breathing (SDB), and atrial fibrillation (AF) is causal or mediated by shared co-morbidities such as obesity. Existing observational studies are conflicting and limited by confounding and reverse causality. We performed Mendelian randomisation (MR) to investigate the causal relationships between SDB, body mass index (BMI) and AF. Single-nucleotide polymorphisms associated with SDB (n = 29) and BMI (n = 453) were selected as instrumental variables to investigate the effects of SDB and BMI on AF, using genetic association data on 55,114 AF cases and 482,295 controls. Primary analysis was conducted using inverse-variance weighted MR. Higher genetically predicted SDB and BMI were associated with increased risk of AF (OR per log OR increase in snoring liability 2.09 (95% CI 1.10–3.98), p = 0.03; OR per 1-SD increase in BMI 1.33 (95% CI 1.24–1.42), p < 0.001). The association between SDB and AF was not observed in sensitivity analyses, whilst associations between BMI and AF remained consistent. Similarly, in multivariable MR, SDB was not associated with AF after adjusting for BMI (OR 0.68 (95% CI 0.42–1.10), p = 0.12). Higher BMI remained associated with increased risk of AF after adjusting for OSA (OR 1.40 (95% CI 1.30–1.51), p < 0.001). Elevated BMI appears causal for AF, independent of SDB. Our data suggest that the association between SDB, in general, and AF is attributable to mediation or confounding from obesity, though we cannot exclude that more severe SDB phenotypes (i.e., OSA) are causal for AF.

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 Psychometric properties and correlates of Chinese version of Perceived Stress Scale (CPSS-10) in people with common mental disorders with different employment Statuses

2021 ◽  
pp. 156918612110323
Author(s):  
Sam Shih ◽  
Ashley Chan ◽  
Eva Yeung ◽  
Amily Tsang ◽  
Rose Chiu ◽  
...  
Keyword(s):  
Mental Disorders ◽  
Psychometric Properties ◽  
Perceived Stress ◽  
Internal Consistency ◽  
Assessment Tool ◽  
Common Mental Disorders ◽  
Linear Regression Analysis ◽  
Chinese Version ◽  
Perceived Stress Scale ◽  
Stress Scale

Background/objectives Several studies have indicated that stress is associated with common mental disorders, and work stress trebles the risk of developing them. However, a validated assessment tool for measuring and establishing psychological stress correlates in this group of clients remains unavailable. The objectives of the present study were to examine the psychometric properties of the Chinese version of the Perceived Stress Scale-10 (CPSS-10) on people with common mental disorders with different employment statuses and explore its correlates. Methods Two hundred and fifty-two participants with common mental disorders were recruited. The data were analysed through exploratory factor and confirmatory analyses to investigate construct validity. The convergent and discriminant validities were examined based on their correlation with other measures, while the internal consistency was estimated using Cronbach’s α coefficient. A t-test was used to detect differences between groups. The CPSS-10 correlates were explored using multiple linear regression analysis. Results Principal component analysis with varimax rotation yielded two factors, which accounted for 63.82% of the total variance, while confirmatory factor analysis confirmed its factor structure. The CPSS-10 had a positively moderate to strong correlation with other measures, thereby indicating its acceptable convergent and discriminant validities. The internal consistency ranged from acceptable to good for the two subscales and ten overall items, while the item-total correlation was adequate except for the seventh item. There were no group differences in gender nor employment status. Finally, the CPSS-10 predictors were studied. Conclusion The CPSS-10 is a reliable and valid instrument for people with common mental disorders with different employment statuses.

scholarly journals Mendelian randomisation for mediation analysis: current methods and challenges for implementation

2021 ◽  
Author(s):  
Alice R. Carter ◽  
Eleanor Sanderson ◽  
Gemma Hammerton ◽  
Rebecca C. Richmond ◽  
George Davey Smith ◽  
...  
Keyword(s):  
Measurement Error ◽  
Causal Inference ◽  
Mediation Analysis ◽  
Instrumental Variable ◽  
Real Data ◽  
Mendelian Randomisation ◽  
Differential Measurement ◽  
Individual Level ◽  
Differential Measurement Error ◽  
Summary Data

AbstractMediation analysis seeks to explain the pathway(s) through which an exposure affects an outcome. Traditional, non-instrumental variable methods for mediation analysis experience a number of methodological difficulties, including bias due to confounding between an exposure, mediator and outcome and measurement error. Mendelian randomisation (MR) can be used to improve causal inference for mediation analysis. We describe two approaches that can be used for estimating mediation analysis with MR: multivariable MR (MVMR) and two-step MR. We outline the approaches and provide code to demonstrate how they can be used in mediation analysis. We review issues that can affect analyses, including confounding, measurement error, weak instrument bias, interactions between exposures and mediators and analysis of multiple mediators. Description of the methods is supplemented by simulated and real data examples. Although MR relies on large sample sizes and strong assumptions, such as having strong instruments and no horizontally pleiotropic pathways, our simulations demonstrate that these methods are unaffected by confounders of the exposure or mediator and the outcome and non-differential measurement error of the exposure or mediator. Both MVMR and two-step MR can be implemented in both individual-level MR and summary data MR. MR mediation methods require different assumptions to be made, compared with non-instrumental variable mediation methods. Where these assumptions are more plausible, MR can be used to improve causal inference in mediation analysis.

Abstract P262: Spot Urine Sodium to Potassium Ratio Predicts Increasing Blood Pressure Levels in a General Population: The Nagahama Study

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Yasuharu Tabara ◽  
Yoshimitsu Takahashi ◽  
Takeo Nakayama ◽  
Fumihiko Matsuda
Keyword(s):  
Blood Pressure ◽  
Salt Intake ◽  
Linear Regression Analysis ◽  
Prognostic Significance ◽  
Reverse Causality ◽  
Cross Sectional ◽  
Salt Loading ◽  
Available N ◽  
Spot Urine

Excessive salt intake is a risk factor for hypertension. The most reliable method for estimating daily salt intake is measurement of 24-h urinary sodium excretion, while it is inconvenient. Sodium-to-potassium ratio (Na/K) of a urine sample is another index of salt loading. We previously reported that a simple measure of spot urine Na/K might be a representative of salt loading in a cross-sectional setting. Here, we conducted a longitudinal study aiming to clarify a prognostic significance of spot urine Na/K for increasing blood pressure (BP) levels. Study subjects consists of 9,769 general individuals. Among them, individuals whose baseline Na/K was available (n=9,328), who were normotensive at baseline (n=6,392), and who participated in the follow-up measurement (n=5,209) were included in this analysis (51.8±12.9 years old, male: 29.2%). Mean follow-up duration was 5.0±0.5 years. Mean Na/K at baseline was 3.1±1.7, and showed step-wise increase with BP levels (optimal: 3.0±1.6, normal: 3.3±1.8, high normal: 3.4±1.8, P<0.001). Other major factors that were significantly associated with Na/K was fasting time (r=-0.220, P<0.001), and CKD (CKD (n=694): 2.7±1.6, control: 3.2±1.7, P<0.001). Mean SBP was significantly increased during follow-up period (baseline: 116±12, follow-up: 119±15 mmHg), and 805 individuals (15.5%) were newly diagnosed as hypertension (HT). These individuals were significantly older (HT: 60.3±9.9, NT: 50.3±12.8 years), were frequently male (36.4%, 27.9%), and had higher SBP (127±9, 115±11 mmHg) at baseline (P<0.001). In contrast, baseline spot urine Na/K was slightly lower in individuals who developed HT (3.0±1.6, 3.1±1.8, P=0.013), while that measured at follow-up investigation was oppositely higher in hypertensives (3.1±1.8, 2.8±1.5, P<0.001). Multiple linear regression analysis adjusted for the covariates identified baseline Na/K (β=0.108, P<0.001) and changes in Na/K during follow-up period (β=0.222, P<0.001) as independent determinants for future SBP levels. Higher spot urine Na/K, as well as increases in the Na/K levels, was significant determinant for future BP levels. The apparently lower baseline Na/K levels in individuals who developed HT might be due to reverse causality.

Excess mortality of mental disorder

1998 ◽  
Vol 173 (1) ◽  
pp. 11-53 ◽  
Author(s):  
Clare Harris ◽  
Brian Barraclough
Keyword(s):  
Mental Disorders ◽  
Mental Disorder ◽  
English Language ◽  
Common Mental Disorders ◽  
Premature Death ◽  
Medline Search ◽  
Risk Of Death ◽  
Increased Risk ◽  
Standardised Mortality Ratios ◽  
The Common

BackgroundWe describe the increased risk of premature death from natural and from unnatural causes for the common mental disorders.MethodWith a Medline search (1966–1995) we found 152 English language reports on the mortality of mental disorder which met our inclusion criteria. From these reports, covering 27 mental disorder categories and eight treatment categories, we calculated standardised mortality ratios (SMRs) and 95% confidence intervals (CIs) for all causes of death, all natural causes and all unnatural causes; and for most, SMRs for suicide, other violent causes and specific natural causes.ResultsHighest risks of premature death, from both natural and unnatural causes, are for substance abuse and eating disorders. Risk of death from unnatural causes is especially high for the functional disorders, particularly schizophrenia and major depression. Deaths from natural causes are markedly increased for organic mental disorders, mental retardation and epilepsy.ConclusionAll mental disorders have an increased risk of premature death.

scholarly journals Association of ABO haplotypes with the risk of venous thrombosis: impact on disease risks estimation

Blood ◽  
2020 ◽  
Author(s):  
Louisa Goumidi ◽  
Florian Thibord ◽  
Kerri L. Wiggins ◽  
Ruifang Li-Gao ◽  
Michael R Brown ◽  
...  
Keyword(s):  
Venous Thrombosis ◽  
Blood Group ◽  
Plasma Levels ◽  
Odds Ratio ◽  
Prediction Models ◽  
Genetic Risk Score ◽  
Individual Risk ◽  
Abo Blood Group ◽  
Increased Risk ◽  
The Impact

Genetic risk score (GRS) analysis is an increasingly popular approach to derive individual risk prediction models for complex diseases. In the context of venous thrombosis (VT), any GRS shall integrate information at the ABO blood group locus, the latter being one of the major susceptibility locus for this disease. However, there is yet no consensus about which single nucleotide polymorphisms (SNPs) must be investigated when one is interested in properly assessing the association of ABO locus with VT risk. Using comprehensive haplotype analyses of ABO blood group tagging SNPs in up to 5,425 cases and 8,445 controls from 6 studies, we demonstrated that using only rs8176719 (tagging O1) to correctly assess the impact of ABO locus on VT risk is suboptimal as 5% of rs8176719-delG carriers are not exposed at higher VT risk. Instead, we recommend to use 4 SNPs, rs2519093 (tagging A1), rs1053878 (A2), rs8176743 (B) and rs41302905 (O2) in any analysis aimed at assessing the impact of ABO locus on VT risk to avoid any risk misestimation. Compared to O1 haplotype that can be inferred from these 4 SNPs, the A2 haplotype is associated with a modest increase in VT risk (odds ratio ~1.2), A1 and B haplotypes are associated with a ~1.8 fold increased risk while O2 tend to be slightly protective (odds ratio ~0.80). In addition, our analyses clearly showed that while the A1 an B blood group are associated with increased vWF and FVIII plasma levels only the A1 blood group is associated wih ICAM plasma levels but in an opposite direction, leaving additional avenues to be explored in order to fully understand the whole spectrum of biological effect of ABO locus on cardiovascular traits.

scholarly journals When can be safely performed total knee arthroplasty following prior arthroscopy?

2020 ◽  
Author(s):  
Jin-Ning Ma ◽  
Xiao-Lin Li ◽  
Pan Liang ◽  
Sheng-Li Yu
Keyword(s):  
Total Knee Arthroplasty ◽  
Postoperative Complications ◽  
Knee Arthroplasty ◽  
Linear Regression Analysis ◽  
Acl Injury ◽  
Optimal Time ◽  
Control Group ◽  
Complication Rates ◽  
Increased Risk ◽  
Total Knee

Abstract Background The optimal time to perform a total knee arthroplasty (TKA) after knee arthroscopy (KA) was controversial in the literature. We aimed to 1) explore the effect of prior KA on the subsequent TKA; 2) identify who were not suitable for TKA in patients with prior KA; and 3) determine the timing of TKA following prior KA.Methods We retrospectively reviewed 87 TKAs with prior KA and 174 controls using propensity score matching in our institution. The minimum followup was 2 years. Postoperative clinical outcomes were compared between groups. Kaplan-Meier curves were created with reoperation as an end point. Multivariate Cox proportional hazards regressions were performed to identify risk factors of severe complications in the KA group. The two-piecewise linear regression analysis was performed to examine the optimal timing of TKA following prior KA.Results The all-cause reoperation, revision and complication rates of KA group were significantly higher than those of control group (p<0.05). The survivorship of KA group and control group was 92.0% and 99.4% at the 2-year followup (p=0.002), respectively. Male (Hazards ratio [HR]=3.2) and prior KA for anterior cruciate ligament (ACL) injury (HR=4.4) were associated with postoperative complications in the KA group. There was a non-liner relationship between time from prior KA to TKA and postoperative complications with the turning point at 9.4 months.Conclusion Prior KA is associated with worse outcomes following subsequent TKA, especially male patients and those with prior KA for ACL injury. There is an increased risk of postoperative complications when TKA is performed within 9 months of KA. Surgeons should keep these findings in mind when treating patients who are scheduled to undergo TKA with prior KA.

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