scholarly journals Role of Inflammation in Depression and Anxiety: Tests for Disorder Specificity, Linearity and Potential Causality of Association in the UK Biobank

2021 ◽  
Author(s):  
Zheng Ye ◽  
Nils Kappelmann ◽  
Sylvain Moser ◽  
George Davey Smith ◽  
Stephen Burgess ◽  
...  
Keyword(s):  
Anxiety Symptom ◽  
Experimental Studies ◽  
Mendelian Randomisation ◽  
Depression And Anxiety ◽  
Uk Biobank ◽  
Reactive Protein ◽  
Increased Risk ◽  
Symptom Scores ◽  
Using Data ◽  
The Uk

ABSTRACTBackgroundConcentrations of C-reactive protein (CRP), interleukin 6 (IL-6) and other inflammatory markers are elevated in people with depression and anxiety compared to controls, but evidence for disorder-specificity, linearity and potential causality is sparse.MethodsUsing data from up to 144,890 UK Biobank cohort participants, we tested associations of circulating CRP concentrations with depression and anxiety symptom scores and probable diagnosis, including tests for linearity, disorder-specificity and sex difference. We examined potential causality using 1-sample and 2-sample Mendelian randomisation (MR) analyses testing associations of genetically-predicted CRP concentration and IL-6 activity with depression and anxiety.FindingsCRP concentration was associated with depressive and anxiety symptom scores and with probable diagnoses of depression and generalised anxiety disorder (GAD) in a dose-response fashion. These associations were stronger for depression than for anxiety, and for women than for men although less consistently. MR analyses provided consistent results suggesting that genetically predicted higher IL-6 activity was associated with increased risk for depressive symptoms, while genetically-predicted higher CRP concentration was associated with decreased risks of depressive and anxiety symptoms.InterpretationAltered activity of the IL-6/IL-6R pathway could be causally linked to depression. The field now requires experimental studies of IL-6 modulation in humans and animal models to further examine causality, mechanisms and treatment potential. Such studies are also needed to elucidate mechanisms for divergent associations of genetically-predicted higher IL-6 activity (risk increasing) and higher CRP concentrations (protective) with depression/anxiety.FundingMQ (MQDS17/40); Wellcome Trust (201486/Z/16/Z).

scholarly journals Association of inflammation with depression and anxiety: evidence for symptom-specificity and potential causality from UK Biobank and NESDA cohorts

2021 ◽  
Author(s):  
Yuri Milaneschi ◽  
Nils Kappelmann ◽  
Zheng Ye ◽  
Femke Lamers ◽  
Sylvain Moser ◽  
...  
Keyword(s):  
Depressive Symptoms ◽  
Sleep Problems ◽  
Experimental Studies ◽  
Anxiety Symptoms ◽  
Self Report ◽  
Mendelian Randomisation ◽  
Depression And Anxiety ◽  
Uk Biobank ◽  
Increased Risk ◽  
The Uk

AbstractWe examined whether inflammation is uniformly associated with all depressive and anxiety symptoms, and whether these associations are potentially causal. Data was from 147,478 individuals from the UK Biobank (UKB) and 2,905 from the Netherlands Study of Depression and Anxiety (NESDA). Circulating C-reactive protein (CRP) was measured in both cohorts and interleukin-6 (IL-6) in NESDA. Genetic instruments for these proteins were obtained from published GWAS and UKB. Depressive and anxiety symptoms were assessed with self-report questionnaires. In NESDA, neurovegetative (appetite, sleep, psychomotor) symptoms were disaggregated as increased vs. decreased. In joint analyses, higher CRP was associated with depressive symptoms of depressed mood (OR = 1.06, 95% CI = 1.05–1.08), altered appetite (OR = 1.25, 95%CI = 1.23–1.28), sleep problems (OR = 1.05, 95%CI = 1.04–1.06), and fatigue (OR = 1.12, 95% CI = 1.11–1.14), and with anxiety symptoms of irritability (OR = 1.06, 95% CI = 1.05–1.08) and worrying control (OR = 1.03, 95% CI = 1.02–1.04). In NESDA, higher IL-6 was additionally associated with anhedonia (OR = 1.30, 95% CI = 1.12–1.52). Higher levels of both CRP (OR = 1.27, 95% CI = 1.13–1.43) and IL-6 (OR = 1.26, 95% CI = 1.07–1.49) were associated with increased sleep. Higher CRP was associated with increased appetite (OR = 1.21, 95% CI = 1.08–1.35) while higher IL-6 with decreased appetite (OR = 1.45, 95% CI = 1.18–1.79). In Mendelian Randomisation analyses, genetically predicted higher IL-6 activity was associated with increased risk of fatigue (estimate = 0.25, SE = 0.08) and sleep problems (estimate = 0.19, SE = 0.07). Inflammation was associated with core depressive symptoms of low mood and anhedonia and somatic/neurovegetative symptoms of fatigue, altered sleep and appetite changes. Less consistent associations were found for anxiety. The IL-6/IL-6R pathway could be causally linked to depression. Experimental studies are required to further evaluate causality, mechanisms, and usefulness of immunotherapies for depressive symptoms.

Body size and composition and site-specific cancers in UK Biobank: a Mendelian randomisation study

2020 ◽  
Author(s):  
Mathew Vithayathil ◽  
Paul Carter ◽  
Siddhartha Kar ◽  
Amy M. Mason ◽  
Stephen Burgess ◽  
...  
Keyword(s):  
Instrumental Variables ◽  
Association Studies ◽  
Genome Wide Association ◽  
Mendelian Randomisation ◽  
Genome Wide Association Studies ◽  
Uk Biobank ◽  
Site Specific ◽  
Genome Wide ◽  
Increased Risk ◽  
The Uk

ABSTRACTObjectivesTo investigate the casual role of body mass index, body fat composition and height in cancer.DesignTwo stage mendelian randomisation studySettingPrevious genome wide association studies and the UK BiobankParticipantsGenetic instrumental variables for body mass index (BMI), fat mass index (FMI), fat free mass index (FFMI) and height from previous genome wide association studies and UK Biobank. Cancer outcomes from 367 586 participants of European descent from the UK Biobank.Main outcome measuresOverall cancer risk and 22 site-specific cancers risk for genetic instrumental variables for BMI, FMI, FFMI and height.ResultsGenetically predicted BMI (per 1 kg/m2) was not associated with overall cancer risk (OR 0.99; 95% confidence interval (CI) 0-98-1.00, p=0.105). Elevated BMI was associated with increased risk of stomach cancer (OR 1.15, 95% (CI) 1.05-1.26; p=0.003) and melanoma (OR 0.96, 95% CI 0.92-1.00; p=0.044). For sex-specific cancers, BMI was positively associated with uterine cancer (OR 1.08, 95% CI 1.01-1.14; p=0.015) but inversely associated with breast (OR 0.95, 95% CI 0.92-0.98; p=0.001), prostate (OR 0.95, 95% CI 0.92-0.99; p=0.007) and testicular cancer (OR 0.89, 95% CI 0.81-0.98; p=0.017). Elevated FMI (per 1 kg/m2) was associated with gastrointestinal cancer (stomach cancer OR 4.23, 95% CI 1.18-15.13, p=0.027; colorectal cancer OR 1.94, 95% CI 1.23-3.07; p=0.004). Increased height (per 1 standard deviation, approximately 6.5cm) was associated with increased risk of overall cancer (OR 1.06; 95% 1.04-1.09; p = 2.97×10-8) and most site-specific cancers with the strongest estimates for kidney, non-Hodgkin lymphoma, colorectal, lung, melanoma and breast cancer.ConclusionsThere is little evidence for BMI as a casual risk factor for cancer. BMI may have a causal role for sex-specific cancers, although with inconsistent directions of effect, and FMI for gastrointestinal malignancies. Elevated height is a risk factor for overall cancer and multiple site cancers.

scholarly journals Trends in depression & anxiety symptom severity among mental health service attendees during the COVID-19 pandemic

2021 ◽  
Author(s):  
Rob Saunders ◽  
Joshua Eusty Jonathan Buckman ◽  
Judy Leibowitz ◽  
John Cape ◽  
Stephen Pilling
Keyword(s):  
Mental Health ◽  
Anxiety Symptom ◽  
Psychological Treatment ◽  
Depression And Anxiety ◽  
Treatment Services ◽  
Symptom Scores ◽  
Potential Benefits ◽  
Community Transmission ◽  
The Uk ◽  
Residual Confounding

BackgroundGeneral population surveys have shown that some groups, particularly young women experienced increased distress during nationally mandated restrictions to control the spread of COVID-19. However, there has been limited research on such trends among people with pre-existing mental health conditions, leaving mental health services ill equipped to plan for currents and future lockdowns.MethodsMean weekly scores on the GAD-7 and PHQ-9 between 01/01/2020-22/06/2020 (n=9,538 individuals) for all patients of two psychological treatment services in London, were compared to mean weekly scores from the same time periods in 2017-2019 (n=37,849). The proportion of scores which were above the clinical thresholds for ‘caseness’ each week were compared, and scores between groups based on gender, age group, and ethnicity, were also compared. ResultsConfirmed community transmission in the UK (26/02/2020-03/03/2020) and the announcement of the national ‘lockdown’ (23/03/2020) were associated with significant increases in anxiety symptom scores. ‘Lockdown’ was associated with a decrease in depression scores. These changes were not maintained during lockdown. Significant increases in depression and anxiety were observed at week 23, as restrictions were eased.LimitationsThis was an exploratory analysis in two services only. Residual confounding and selection biases cannot be ruled out.ConclusionsDifferences in the weekly average symptom scores were short-term; they did not continue throughout ‘lockdown’ as might have been expected, except among older people. Replication of this study in other settings and investigating the potential benefits of more regular reviews or more intensive treatments for older adults seeking support, are warranted.

scholarly journals Genetic liability to insomnia in relation to cardiovascular diseases: a Mendelian randomisation study

2021 ◽  
Author(s):  
Shuai Yuan ◽  
Amy M. Mason ◽  
Stephen Burgess ◽  
Susanna C. Larsson
Keyword(s):  
Cardiovascular Diseases ◽  
Association Studies ◽  
European Ancestry ◽  
Mendelian Randomisation ◽  
Genome Wide Association Studies ◽  
Uk Biobank ◽  
Genetic Liability ◽  
Genome Wide ◽  
Increased Risk ◽  
The Uk

AbstractThe present study aimed to determine the associations between insomnia and cardiovascular diseases (CVDs) using Mendelian randomisation (MR) analysis. As instrumental variables, we used 208 independent single-nucleotide polymorphisms associated with insomnia at the genome-wide significance threshold in a meta-analysis of genome-wide association studies in the UK Biobank and 23andMe including a total of 397 959 self-reported insomnia cases and 933 057 non-cases. Summary-level data for nine CVDs were obtained from the UK Biobank including 367 586 individuals of European ancestry. After correction for multiple testing, genetic liability to insomnia was associated with higher odds of six CVDs, including peripheral arterial disease (odd ratio (OR) 1.22; 95% confidence interval (CI), 1.21, 1.33), heart failure (OR 1.21; 95% CI, 1.13, 1.30), coronary artery disease (OR 1.19; 95% CI, 1.14, 1.25), ischaemic stroke (OR 1.15; 95% CI, 1.06, 1.25), venous thromboembolism (OR 1.13; 95% CI, 1.07, 1.19) and atrial fibrillation (OR 1.10; 95% CI, 1.05, 1.15). There were suggestive associations for aortic valve stenosis (OR, 1.17; 95% CI, 1.04, 1.32) and haemorrhagic stroke (OR 1.14; 95% CI, 1.00, 1.29) but no association for abdominal aortic aneurysm (OR, 1.14, 95% CI, 0.98, 1.33). The patterns of associations remained with mild attenuation in multivariable MR analyses adjusting for genetically correlated phenotypes and potential mediators, including sleep duration, depression, body mass index, type 2 diabetes and smoking. The present MR study suggests potential causal associations of genetic liability to insomnia with increased risk of a broad range of CVDs.

scholarly journals Influence of blood pressure on pneumonia risk: Epidemiological association and Mendelian randomisation in the UK Biobank

2020 ◽  
Author(s):  
Seyedeh M. Zekavat ◽  
Michael Honigberg ◽  
James Pirruccello ◽  
Puja Kohli ◽  
Elizabeth W. Karlson ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Observational Studies ◽  
Mendelian Randomisation ◽  
List Type ◽  
Uk Biobank ◽  
Increased Risk ◽  
Reduce Risk ◽  
Novel Coronavirus ◽  
The Uk

AbstractObjectivesTo determine whether elevated blood pressure influences risk for respiratory infection.DesignProspective, population-based epidemiological and Mendelian randomisation studies.SettingUK Biobank.Participants377,143 self-identified British descent (54% women; median age 58 years) participants in the UK Biobank.Main outcome measuresFirst incident pneumonia over an average of 8 follow-up years.Results107,310 (30%) participants had hypertension at UK Biobank enrolment, and 9,969 (3%) developed a pneumonia during follow-up. Prevalent hypertension at baseline was significantly associated with increased risk for incident respiratory disease including pneumonia (hazard ratio 1.36 (95% confidence interval 1.29 to 1.43), P<0.001), acute respiratory distress syndrome or respiratory failure (1.43 (1.29 to 1.59), P<0.001), and chronic lower respiratory disease (1.30 (1.25 to 1.36), P<0.001), independent of age, age2, sex, smoking status, BMI, prevalent diabetes mellitus, prevalent coronary artery disease, and principal components of ancestry. Mendelian randomisation analyses indicated that genetic predisposition to a 5 mmHg increase in blood pressure was associated with increased risk of incident pneumonia for SBP (1.08, (1.04 to 1.13), P<0.001) and DBP (1.11 (1.03 to 1.20), P=0.005). Additionally, consistent with epidemiologic associations, increase in blood pressure genetic risk was significantly associated with reduced forced expiratory volume in the first second, forced vital capacity, and the ratio of the two (P<0.001 for all).ConclusionsThese results strongly suggest that elevated blood pressure independently increases risk for pneumonia and reduces pulmonary function. Maintaining adequate blood pressure control, in addition to other measures, may reduce risk for pneumonia. Whether the present findings are generalizable to novel coronavirus disease 2019 (COVID-19) require further study.Summary BoxSection 1: What is already known on this topicHypertension has been associated with pneumonia in small observational studies.Based on early epidemiologic analyses, hypertension is described as a risk factor for SARS-CoV-2 infection and associated novel coronavirus disease 2019 (COVID-19).The influence of hypertension on pneumonia risk is difficult to assess in traditional observational studies.Section 2: What this study addsOur pre-COVID-19 analyses are consistent with a causal relationship between increased blood pressure and increased risk for incident respiratory infections, as well as between increased blood pressure and reduced pulmonary function.These results support hypertension as a pneumonia risk factor; efforts to optimize blood pressure may reduce risk for pneumonia.

scholarly journals Alcohol causes an increased risk of head and neck but not breast cancer in individuals from the UK Biobank study: A Mendelian randomisation analysis

2019 ◽  
Author(s):  
Nathan Ingold ◽  
Hasnat A Amin ◽  
Fotios Drenos
Keyword(s):  
Breast Cancer ◽  
Alcohol Consumption ◽  
Head And Neck ◽  
Causal Effect ◽  
Head And Neck Cancers ◽  
Mendelian Randomisation ◽  
Uk Biobank ◽  
Increased Risk ◽  
The Uk ◽  
Risk Of Cancer

ABSTACTAlcohol intake and the risk of various types of cancers have been previously correlated. Correlation though does not always mean that a causal relationship between the two is present. Excessive alcohol consumption is also correlated with other lifestyle factors and behaviours, such as smoking and increased adiposity, that also affect the risk of cancer and make the identification and estimation of the causal effect of alcohol on cancer difficult. Here, using individual level data for 322,193 individuals from the UK Biobank, we report the observational and causal effects of alcohol consumption on types of cancer previously suggested as correlated to alcohol. Alcohol was observationally associated with cancers of the lower digestive system, head and neck and breast cancer. No associations were observed when we considered those keeping alcohol consumption below the recommended threshold of 14 units/week. When Mendelian randomisation was used to assess the causal effect of alcohol on cancer, we found that increasing alcohol consumption, especially above the recommended level, was causal to head and neck cancers but not breast cancer. Our results where replicated using a two sample MR method and data from the much larger COGS genome wide analysis of breast cancer. We conclude that alcohol is causally related to head and neck cancers, especially cancer of larynx, but the observed association with breast cancer are likely due to confounding. The suggested threshold of 14 units/week appears suitable to manage the risk of cancer due to alcohol.

scholarly journals Body size and composition and risk of site-specific cancers in the UK Biobank and large international consortia: A mendelian randomisation study

PLoS Medicine ◽  
2021 ◽  
Vol 18 (7) ◽  
pp. e1003706
Author(s):  
Mathew Vithayathil ◽  
Paul Carter ◽  
Siddhartha Kar ◽  
Amy M. Mason ◽  
Stephen Burgess ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Risk ◽  
Digestive System ◽  
Uterine Cancer ◽  
Mendelian Randomisation ◽  
Inverse Association ◽  
Uk Biobank ◽  
Site Specific ◽  
Increased Risk ◽  
The Uk

Background Evidence for the impact of body size and composition on cancer risk is limited. This mendelian randomisation (MR) study investigates evidence supporting causal relationships of body mass index (BMI), fat mass index (FMI), fat-free mass index (FFMI), and height with cancer risk. Methods and findings Single nucleotide polymorphisms (SNPs) were used as instrumental variables for BMI (312 SNPs), FMI (577 SNPs), FFMI (577 SNPs), and height (293 SNPs). Associations of the genetic variants with 22 site-specific cancers and overall cancer were estimated in 367,561 individuals from the UK Biobank (UKBB) and with lung, breast, ovarian, uterine, and prostate cancer in large international consortia. In the UKBB, genetically predicted BMI was positively associated with overall cancer (odds ratio [OR] per 1 kg/m2 increase 1.01, 95% confidence interval [CI] 1.00–1.02; p = 0.043); several digestive system cancers: stomach (OR 1.13, 95% CI 1.06–1.21; p < 0.001), esophagus (OR 1.10, 95% CI 1.03, 1.17; p = 0.003), liver (OR 1.13, 95% CI 1.03–1.25; p = 0.012), and pancreas (OR 1.06, 95% CI 1.01–1.12; p = 0.016); and lung cancer (OR 1.08, 95% CI 1.04–1.12; p < 0.001). For sex-specific cancers, genetically predicted elevated BMI was associated with an increased risk of uterine cancer (OR 1.10, 95% CI 1.05–1.15; p < 0.001) and with a lower risk of prostate cancer (OR 0.97, 95% CI 0.94–0.99; p = 0.009). When dividing cancers into digestive system versus non-digestive system, genetically predicted BMI was positively associated with digestive system cancers (OR 1.04, 95% CI 1.02–1.06; p < 0.001) but not with non-digestive system cancers (OR 1.01, 95% CI 0.99–1.02; p = 0.369). Genetically predicted FMI was positively associated with liver, pancreatic, and lung cancer and inversely associated with melanoma and prostate cancer. Genetically predicted FFMI was positively associated with non-Hodgkin lymphoma and melanoma. Genetically predicted height was associated with increased risk of overall cancer (OR per 1 standard deviation increase 1.09; 95% CI 1.05–1.12; p < 0.001) and multiple site-specific cancers. Similar results were observed in analyses using the weighted median and MR–Egger methods. Results based on consortium data confirmed the positive associations between BMI and lung and uterine cancer risk as well as the inverse association between BMI and prostate cancer, and, additionally, showed an inverse association between genetically predicted BMI and breast cancer. The main limitations are the assumption that genetic associations with cancer outcomes are mediated via the proposed risk factors and that estimates for some lower frequency cancer types are subject to low precision. Conclusions Our results show that the evidence for BMI as a causal risk factor for cancer is mixed. We find that BMI has a consistent causal role in increasing risk of digestive system cancers and a role for sex-specific cancers with inconsistent directions of effect. In contrast, increased height appears to have a consistent risk-increasing effect on overall and site-specific cancers.

scholarly journals Impact of replacing sedentary behaviour with other movement behaviours on depression and anxiety symptoms: a prospective cohort study in the UK Biobank

BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
A. A. Kandola ◽  
B. del Pozo Cruz ◽  
D. P. J. Osborn ◽  
B. Stubbs ◽  
K. W. Choi ◽  
...  
Keyword(s):  
Sedentary Behaviour ◽  
Anxiety Symptom ◽  
Anxiety Symptoms ◽  
Vigorous Activity ◽  
Depression And Anxiety ◽  
Uk Biobank ◽  
Lower Odds ◽  
Symptom Scores ◽  
Light Activity

Abstract Background Sedentary behaviour is potentially a modifiable risk factor for depression and anxiety disorders, but findings have been inconsistent. To assess the associations of sedentary behaviour with depression and anxiety symptoms and estimate the impact of replacing daily time spent in sedentary behaviours with sleep, light, or moderate to vigorous physical activity, using compositional data analysis methods. Methods We conducted a prospective cohort study in 60,235 UK Biobank participants (mean age: 56; 56% female). Exposure was baseline daily movement behaviours (accelerometer-assessed sedentary behaviour and physical activity, and self-reported total sleep). Outcomes were depression and anxiety symptoms (Patient Health Questionnaire-9 and Generalised Anxiety Disorders-7) at follow-up. Results Replacing 60 min of sedentary behaviour with light activity, moderate-to-vigorous activity, and sleep was associated with lower depression symptom scores by 1.3% (95% CI, 0.4–2.1%), 12.5% (95% CI, 11.4–13.5%), and 7.6% (95% CI, 6.9–8.4%), and lower odds of possible depression by 0.95 (95% CI, 0.94–0.96), 0.75 (95% CI, 0.74–0.76), and 0.90 (95% CI, 0.90–0.91) at follow-up. Replacing 60 min of sedentary behaviour with moderate-to-vigorous activity and sleep was associated with lower anxiety symptom scores by 6.6% (95% CI, 5.5–7.6%) and 4.5% (95% CI, 3.7–5.2%), and lower odds of meeting the threshold for a possible anxiety disorder by 0.90 (95% CI, 0.89–0.90) and 0.97 (95%CI, 0.96–0.97) at follow-up. However, replacing 60 min of sedentary behaviour with light activity was associated with higher anxiety symptom scores by 4.5% (95% CI, 3.7–5.3%) and higher odds of a possible anxiety disorder by 1.07 (95% CI, 1.06–1.08). Conclusions Sedentary behaviour is a risk factor for increased depression and anxiety symptoms in adults. Replacing sedentary behaviour with moderate-to-vigorous activity may reduce mental health risks, but more work is necessary to clarify the role of light activity.

scholarly journals Socioeconomic Inequalities and Ethnicity Are Associated with a Positive COVID-19 Test among Cancer Patients in the UK Biobank Cohort

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1514
Author(s):  
Shing Fung Lee ◽  
Maja Nikšić ◽  
Bernard Rachet ◽  
Maria-Jose Sanchez ◽  
Miguel Angel Luque-Fernandez
Keyword(s):  
Cancer Patients ◽  
Socioeconomic Inequalities ◽  
Uk Biobank ◽  
Incident Cancer ◽  
Increased Risk ◽  
Exposure Variable ◽  
Independent Risk Factors ◽  
The Uk ◽  
Deprived Areas

We explored the role of socioeconomic inequalities in COVID-19 incidence among cancer patients during the first wave of the pandemic. We conducted a case-control study within the UK Biobank cohort linked to the COVID-19 tests results available from 16 March 2020 until 23 August 2020. The main exposure variable was socioeconomic status, assessed using the Townsend Deprivation Index. Among 18,917 participants with an incident malignancy in the UK Biobank cohort, 89 tested positive for COVID-19. The overall COVID-19 incidence was 4.7 cases per 1000 incident cancer patients (95%CI 3.8–5.8). Compared with the least deprived cancer patients, those living in the most deprived areas had an almost three times higher risk of testing positive (RR 2.6, 95%CI 1.1–5.8). Other independent risk factors were ethnic minority background, obesity, unemployment, smoking, and being diagnosed with a haematological cancer for less than five years. A consistent pattern of socioeconomic inequalities in COVID-19 among incident cancer patients in the UK highlights the need to prioritise the cancer patients living in the most deprived areas in vaccination planning. This socio-demographic profiling of vulnerable cancer patients at increased risk of infection can inform prevention strategies and policy improvements for the coming pandemic waves.

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