scholarly journals Estimated effects of health conditions and risk factors on social and socioeconomic outcomes: mendelian randomisation of UK Biobank data

The Lancet ◽  
2019 ◽  
Vol 394 ◽  
pp. S49
Author(s):  
Sean Harrison ◽  
Alisha R Davies ◽  
Matt Dickson ◽  
Jessica Tyrrell ◽  
Michael J Green ◽  
...  
2019 ◽  
Author(s):  
Sean Harrison ◽  
Alisha R Davies ◽  
Matt Dickson ◽  
Jessica Tyrrell ◽  
Michael J Green ◽  
...  

AbstractObjectivesTo estimate the causal effect of health conditions and risk factors on social and socioeconomic outcomes in UK Biobank. Evidence on socioeconomic impacts is important to understand because it can help governments, policy-makers and decision-makers allocate resources efficiently and effectively.DesignWe used Mendelian randomization to estimate the causal effects of eight health conditions (asthma, breast cancer, coronary heart disease, depression, eczema, migraine, osteoarthritis, type 2 diabetes) and five health risk factors (alcohol intake, body mass index [BMI], cholesterol, systolic blood pressure, smoking) on 19 social and socioeconomic outcomes.SettingUK Biobank.Participants337,009 men and women of white British ancestry, aged between 39 and 72 years.Main outcome measuresAnnual household income, employment, deprivation (measured by the Townsend deprivation index [TDI]), degree level education, happiness, loneliness, and 13 other social and socioeconomic outcomes.ResultsResults suggested that BMI, smoking and alcohol intake affect many socioeconomic outcomes. For example, smoking was estimated to reduce household income (mean difference = −£24,394, 95% confidence interval (CI): −£33,403 to −£15,384), the chance of owning accommodation (absolute percentage change [APC] = −21.5%, 95% CI: −29.3% to −13.6%), being satisfied with health (APC = −32.4%, 95% CI: −48.9% to −15.8%), and of obtaining a university degree (APC = −73.8%, 95% CI: −90.7% to −56.9%), while also increasing deprivation (mean difference in TDI = 1.89, 95% CI: 1.13 to 2.64, approximately 236% of a decile of TDI). There was evidence that asthma increased deprivation and decreased both household income and the chance of obtaining a university degree, and migraine reduced the chance of having a weekly leisure or social activity, especially in men. For other associations, estimates were null.ConclusionsHigher BMI, alcohol intake and smoking were all estimated to adversely affect multiple social and socioeconomic outcomes. Effects were not detected between health conditions and socioeconomic outcomes using Mendelian randomization, with the exceptions of depression, asthma and migraines. This may reflect true null associations, selection bias given the relative health and age of participants in UK Biobank, and/or lack of power to detect effects.What is known?Studies have shown associations between poor health and adverse social (e.g. wellbeing, social contact) and socioeconomic (e.g. educational attainment, income, employment) outcomes, but there is also strong evidence that social and socioeconomic factors influence health.These bidirectional relationships make it difficult to establish whether health conditions and health risk factors have causal effects on social and socioeconomic outcomes.Mendelian randomization is a technique that uses genetic variants robustly related to an exposure of interest (here, health conditions and risk factors for poor health) as a proxy for the exposure.Since genetic variants are randomly allocated at conception, they tend to be unrelated to the factors that typically confound observational studies, and are less likely to suffer from reverse causality, making causal inference from Mendelian randomization analyses more plausible.What this study addsThis study suggests causal effects of higher BMI, smoking and alcohol use on a range of social and socioeconomic outcomes, implying that population-level improvements in these risk factors may, in addition to the well-known health benefits, have social and socioeconomic benefits for individuals and society.There was evidence that asthma increased deprivation, decreased household income and the chance of having a university degree, migraine reduced the chance of having a weekly leisure or social activity, especially in men, and depression increased loneliness and decreased happiness.There was little evidence for causal effects of cholesterol, systolic blood pressure or breast cancer on social and socioeconomic outcomes.


2020 ◽  
Vol 49 (5) ◽  
pp. 1661-1681 ◽  
Author(s):  
Sean Harrison ◽  
Alisha R Davies ◽  
Matt Dickson ◽  
Jessica Tyrrell ◽  
Michael J Green ◽  
...  

Abstract Background We aimed to estimate the causal effect of health conditions and risk factors on social and socioeconomic outcomes in UK Biobank. Evidence on socioeconomic impacts is important to understand because it can help governments, policy makers and decision makers allocate resources efficiently and effectively. Methods We used Mendelian randomization to estimate the causal effects of eight health conditions (asthma, breast cancer, coronary heart disease, depression, eczema, migraine, osteoarthritis, type 2 diabetes) and five health risk factors [alcohol intake, body mass index (BMI), cholesterol, systolic blood pressure, smoking] on 19 social and socioeconomic outcomes in 336 997 men and women of White British ancestry in UK Biobank, aged between 39 and 72 years. Outcomes included annual household income, employment, deprivation [measured by the Townsend deprivation index (TDI)], degree-level education, happiness, loneliness and 13 other social and socioeconomic outcomes. Results Results suggested that BMI, smoking and alcohol intake affect many socioeconomic outcomes. For example, smoking was estimated to reduce household income [mean difference = -£22 838, 95% confidence interval (CI): -£31 354 to -£14 321] and the chance of owning accommodation [absolute percentage change (APC) = -20.8%, 95% CI: -28.2% to -13.4%], of being satisfied with health (APC = -35.4%, 95% CI: -51.2% to -19.5%) and of obtaining a university degree (APC = -65.9%, 95% CI: -81.4% to -50.4%), while also increasing deprivation (mean difference in TDI = 1.73, 95% CI: 1.02 to 2.44, approximately 216% of a decile of TDI). There was evidence that asthma decreased household income, the chance of obtaining a university degree and the chance of cohabiting, and migraine reduced the chance of having a weekly leisure or social activity, especially in men. For other associations, estimates were null. Conclusions Higher BMI, alcohol intake and smoking were all estimated to adversely affect multiple social and socioeconomic outcomes. Effects were not detected between health conditions and socioeconomic outcomes using Mendelian randomization, with the exceptions of depression, asthma and migraines. This may reflect true null associations, selection bias given the relative health and age of participants in UK Biobank, and/or lack of power to detect effects.


PLoS Medicine ◽  
2020 ◽  
Vol 17 (6) ◽  
pp. e1003137 ◽  
Author(s):  
Kai Xiang Lim ◽  
Frühling Rijsdijk ◽  
Saskia P. Hagenaars ◽  
Adam Socrates ◽  
Shing Wan Choi ◽  
...  

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Ruth K. G. Topless ◽  
Tanya J. Major ◽  
Jose C. Florez ◽  
Joel N. Hirschhorn ◽  
Murray Cadzow ◽  
...  

Abstract Background Prevention of hyperuricaemia (HU) is critical to the prevention of gout. Understanding causal relationships and relative contributions of various risk factors to hyperuricemia is therefore important in the prevention of gout. Here, we use attributable fraction to compare the relative contribution of genetic, dietary, urate-lowering therapy (ULT) and other exposures to HU. We use Mendelian randomisation to test for the causality of diet in urate levels. Methods Four European-ancestry sample sets, three from the general population (n = 419,060) and one of people with gout (n = 6781) were derived from the Database of Genotypes and Phenotypes (ARIC, FHS, CARDIA, CHS) and UK Biobank. Dichotomised exposures to diet, genetic risk variants, BMI, alcohol, diuretic treatment, sex and age were used to calculate adjusted population and average attributable fractions (PAF/AAF) for HU (≥0.42 mmol/L [≥7 mg/dL]). Exposure to ULT was also assessed in the gout cohort. Two sample Mendelian randomisation was done in the UK Biobank using dietary pattern-associated genetic variants as exposure and serum urate levels as outcome. Results Adherence to dietary recommendations, BMI (< 25 kg/m2), and absence of the SLC2A9 rs12498742 urate-raising allele produced PAFs for HU of 20 to 24%, 59 to 69%, and 57 to 64%, respectively, in the three non-gout cohorts. In the gout cohort, diet, BMI, SLC2A9 rs12498742 and ULT PAFs for HU were 12%, 49%, 48%, and 63%, respectively. Mendelian randomisation demonstrated weak causal effects of four dietary habits on serum urate levels (e.g. preferentially drinking skim milk increased urate, β = 0.047 mmol/L, P = 3.78 × 10−8). These effects were mediated by BMI, and they were not significant (P ≥ 0.06) in multivariable models assessing the BMI-independent effect of diet on urate. Conclusions Diet has a relatively minor role in determining serum urate levels and HU. In gout, the use of ULT was the largest attributable fraction tested for HU.


2021 ◽  
Author(s):  
Qingning Wang ◽  
Veryan Codd ◽  
Zahra Raisi-Estabragh ◽  
Crispin Musicha ◽  
Bountziouka Vasiliki ◽  
...  

Background: Older chronological age is the most powerful risk factor for adverse coronavirus disease-19 (COVID-19) outcomes. It is uncertain, however, whether older biological age, as assessed by leucocyte telomere length (LTL), is also associated with COVID-19 outcomes. Methods: We associated LTL values obtained from participants recruited into UK Biobank (UKB) during 2006-2010 with adverse COVID-19 outcomes recorded by 30 November 2020, defined as a composite of any of the following: hospital admission, need for critical care, respiratory support, or mortality. Using information on 131 LTL-associated genetic variants, we conducted exploratory Mendelian randomisation (MR) analyses in UKB to evaluate whether observational associations might reflect cause-and-effect relationships. Findings: Of 6,775 participants in UKB who had tested positive for infection with SARS-CoV-2 in the community, there were 914 (13.5%) with adverse COVID-19 outcomes. The odds ratio (OR) for adverse COVID-19 outcomes was 1.17 (95% CI 1.05-1.31; P=0.004) per 1-SD shorter usual LTL, after adjustment for chronological age, sex and ethnicity. Similar ORs were observed in analyses that: adjusted for additional risk factors; disaggregated the composite outcome and reduced the scope for selection or collider bias. In MR analyses, the OR for adverse COVID-19 outcomes was directionally concordant but non-significant. Interpretation: Shorter LTL, indicative of older biological age, is associated with higher risk of adverse COVID-19 outcomes, independent of several major risk factors for COVID-19 including chronological age. Further data are needed to determine whether this association reflects causality.


SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A273-A273
Author(s):  
Xi Zheng ◽  
Ma Cherrysse Ulsa ◽  
Peng Li ◽  
Lei Gao ◽  
Kun Hu

Abstract Introduction While there is emerging evidence for acute sleep disruption in the aftermath of coronavirus disease 2019 (COVID-19), it is unknown whether sleep traits contribute to mortality risk. In this study, we tested whether earlier-life sleep duration, chronotype, insomnia, napping or sleep apnea were associated with increased 30-day COVID-19 mortality. Methods We included 34,711 participants from the UK Biobank, who presented for COVID-19 testing between March and October 2020 (mean age at diagnosis: 69.4±8.3; range 50.2–84.6). Self-reported sleep duration (less than 6h/6-9h/more than 9h), chronotype (“morning”/”intermediate”/”evening”), daytime dozing (often/rarely), insomnia (often/rarely), napping (often/rarely) and presence of sleep apnea (ICD-10 or self-report) were obtained between 2006 and 2010. Multivariate logistic regression models were used to adjust for age, sex, education, socioeconomic status, and relevant risk factors (BMI, hypertension, diabetes, respiratory diseases, smoking, and alcohol). Results The mean time between sleep measures and COVID-19 testing was 11.6±0.9 years. Overall, 5,066 (14.6%) were positive. In those who were positive, 355 (7.0%) died within 30 days (median = 8) after diagnosis. Long sleepers (&gt;9h vs. 6-9h) [20/103 (19.4%) vs. 300/4,573 (6.6%); OR 2.09, 95% 1.19–3.64, p=0.009), often daytime dozers (OR 1.68, 95% 1.04–2.72, p=0.03), and nappers (OR 1.52, 95% 1.04–2.23, p=0.03) were at greater odds of mortality. Prior diagnosis of sleep apnea also saw a two-fold increased odds (OR 2.07, 95% CI: 1.25–3.44 p=0.005). No associations were seen for short sleepers, chronotype or insomnia with COVID-19 mortality. Conclusion Data across all current waves of infection show that prior sleep traits/disturbances, in particular long sleep duration, daytime dozing, napping and sleep apnea, are associated with increased 30-day mortality after COVID-19, independent of health-related risk factors. While sleep health traits may reflect unmeasured poor health, further work is warranted to examine the exact underlying mechanisms, and to test whether sleep health optimization offers resilience to severe illness from COVID-19. Support (if any) NIH [T32GM007592 and R03AG067985 to L.G. RF1AG059867, RF1AG064312, to K.H.], the BrightFocus Foundation A2020886S to P.L. and the Foundation of Anesthesia Education and Research MRTG-02-15-2020 to L.G.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1337.2-1337
Author(s):  
T. W. Swinnen ◽  
M. Willems ◽  
I. Jonkers ◽  
F. P. Luyten ◽  
J. Vanrenterghem ◽  
...  

Background:The personal and societal burden of knee osteoarthritis (KOA) urges the research community to identify factors that predict its onset and progression. A mechanistic understanding of disease is currently lacking but needed to develop targeted interventions. Traditionally, risk factors for KOA are termed ‘local’ to the joint or ‘systemic’ referring to whole-body systems. There are however clear indications in the scientific literature that contextual factors such as socioeconomic position merit further scientific scrutiny, in order to justify a more biopsychosocial view on risk factors in KOA.Objectives:The aims of this systematic literature review were to assess the inclusion of socioeconomic factors in KOA research and to identify the impact of socioeconomic factors on pain and function in KOA.Methods:Major bibliographic databases, namely Medline, Embase, CINAHL, Web of Science and Cochrane, were independently screened by two reviewers (plus one to resolve conflicts) to identify research articles dealing with socioeconomic factors in the KOA population without arthroplasty. Included studies had to quantify the relationship between socioeconomic factors and pain or function. Main exclusion criteria were: a qualitative design, subject age below 16 years and articles not written in English or Dutch. Methodological quality was assessed via the Cochrane risk of bias tools for randomized (ROB-II) and non-randomized intervention studies (ROBIN-I) and the Newcastle-Ottawa Scale for assessing the quality of non-randomised studies. Due to heterogeneity of studies with respect to outcomes assessed and analyses performed, no meta-analysis was performed.Results:Following de-duplication, 7639 articles were available for screening (120 conflicts resolved without a third reader). In 4112 articles, the KOA population was confirmed. 1906 (25%) were excluded because of knee arthroplasty and 1621 (21%) because of other issues related to the population definition. Socioeconomic factors could not be identified in 4058 (53%) papers and were adjusted for in 211 (3%) articles. In the remaining papers covering pain (n=110) and/or function (n=81), education (62%) and race (37%) were most frequently assessed as socioeconomic factors. A huge variety of mainly dichotomous or ordinal socioeconomic outcomes was found without further methodological justification nor sensitivity analysis to unravel the impact of selected categories. Although the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) was the most popular instrument to assess pain and function, data pooling was not possible as socioeconomic factors estimates were part of multilevel models in most studies. Overall results showed that lower education and African American race were consistent predictors of pain and poor function, but those effects diminished or disappeared when psychological aspects (e.g. discrimination) or poverty estimates were taken into account. When function was assessed using self-reported outcomes, the impact of socioeconomic factors was more clear versus performance-based instruments. Quality of research was low to moderate and the moderating or mediating impact of socioeconomic factors on intervention effects in KOA is understudied.Conclusion:Research on contextual socioeconomic factors in KOA is insufficiently addressed and their assessment is highly variable methodologically. Following this systematic literature review, we can highlight the importance of implementing a standardised and feasible set of socioeconomic outcomes in KOA trials1, as well as the importance of public availability of research databases including these factors. Future research should prioritise the underlying mechanisms in the effect of especially education and race on pain and function and assess its impact on intervention effects to fuel novel (non-)pharmacological approaches in KOA.References:[1]Smith TO et al. The OMERACT-OARSI Core Domain Set for Measurement in Clinical Trials of Hip and/or Knee Osteoarthritis J Rheumatol 2019. 46:981–9.Disclosure of Interests:None declared.


BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Jessica Gong ◽  
Katie Harris ◽  
Sanne A. E. Peters ◽  
Mark Woodward

Abstract Background Sex differences in major cardiovascular risk factors for incident (fatal or non-fatal) all-cause dementia were assessed in the UK Biobank. The effects of these risk factors on all-cause dementia were explored by age and socioeconomic status (SES). Methods Cox proportional hazards models were used to estimate hazard ratios (HRs) and women-to-men ratio of HRs (RHR) with 95% confidence intervals (CIs) for systolic blood pressure (SBP) and diastolic blood pressure (DBP), smoking, diabetes, adiposity, stroke, SES and lipids with dementia. Poisson regression was used to estimate the sex-specific incidence rate of dementia for these risk factors. Results 502,226 individuals in midlife (54.4% women, mean age 56.5 years) with no prevalent dementia were included in the analyses. Over 11.8 years (median), 4068 participants (45.9% women) developed dementia. The crude incidence rates were 5.88 [95% CI 5.62–6.16] for women and 8.42 [8.07–8.78] for men, per 10,000 person-years. Sex was associated with the risk of dementia, where the risk was lower in women than men (HR = 0.83 [0.77–0.89]). Current smoking, diabetes, high adiposity, prior stroke and low SES were associated with a greater risk of dementia, similarly in women and men. The relationship between blood pressure (BP) and dementia was U-shaped in men but had a dose-response relationship in women: the HR for SBP per 20 mmHg was 1.08 [1.02–1.13] in women and 0.98 [0.93–1.03] in men. This sex difference was not affected by the use of antihypertensive medication at baseline. The sex difference in the effect of raised BP was consistent for dementia subtypes (vascular dementia and Alzheimer’s disease). Conclusions Several mid-life cardiovascular risk factors were associated with dementia similarly in women and men, but not raised BP. Future bespoke BP-lowering trials are necessary to understand its role in restricting cognitive decline and to clarify any sex difference.


Author(s):  
Marco Bernardi ◽  
Silvio Romano ◽  
Maria Rosaria Squeo ◽  
Emanuele Guerra ◽  
Paolo Emilio Adami ◽  
...  

Abstract Purpose To test the hypothesis that aerobic fitness is inversely related to the risk of atherosclerotic cardiovascular disease (ACVD) in athletes with locomotor impairments deriving from health conditions, such as spinal cord injury (SCI), lower limb amputation, cerebral palsy, poliomyelitis, and other health conditions different from the previous ones. Methods A total of 68 male athletes who competed in either summer or winter Paralympic games were divided in two health conditions groups (35 with SCI, mean age 37.2 ± 8.0 years, and 33 with different health conditions, mean age 37.8 ± 9.9 years) and in four sport type groups (skill, power, intermittent—mixed metabolism—and endurance). They were evaluated through anthropometric and blood pressure measurements, laboratory blood tests, and graded cardiopulmonary maximal arm cranking exercise test, with oxygen uptake peak (VO2peak) measurement. Cardiovascular risk profile was assessed in each athlete. Results The prevalence of ACVD-risk factors in the overall population was 20.6% for hypertension; 47% and 55.9% for high values of total and LDL cholesterol, respectively; 22.1% for reduce glucose tolerance; and 8.8% for obesity. No difference was found between athletes with and without SCI, while the prevalence of obesity was significantly higher in those practicing skill sports (22.7%, p = 0.035), which was the sport type group with Paralympic athletes with the lowest VO2peak (22.5 ± 5.70 ml kg−1 min−1). VO2peak was lower in athletes with SCI than those with different health conditions (28.6 ± 10.0 vs 33.6 ± 8.9 ml kg−1 min−1p = 0.03), and in those with 3–4 risk factors (19.09 ± 5.34 ml kg−1 min−1) than those with 2 risk factors (27.1 ± 5.50 ml kg−1 min−1), 1 risk factor (31.6 ± 8.55 ml kg−1 min−1), or none (36.4 ± 8.76 ml kg−1 min−1) (p < 0.001). Conclusions The present study suggests that having higher VO2peak seems to offer greater protection against ACVD in individuals with a locomotor impairment. Prescribing physical exercise at an intensity similar to that of endurance and intermittent sports should become a fundamental tool to promote health among people with a locomotor impairment.


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