Approaches to minimising the epidemiological impact of sources of systematic and random variation that may affect biochemistry assay data in UK Biobank

Allen, Naomi E.; Arnold, Matthew; Parish, Sarah; Hill, Michael; Sheard, Simon; Callen, Howard; Fry, Daniel; Moffat, Stewart; Gordon, Mark S.; Welsh, Samantha; Elliott, Paul; Collins, Rory

doi:10.12688/wellcomeopenres.16171.1

Cited by 33 publications

(27 citation statements)

References 24 publications

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“…A recent report from UK Biobank showed consistent mean values and a high self-correlation between baseline and repeated measurements among 20 000 participants for blood lipids and glycated haemoglobin. 45 For an individual, clinical impact of such magnitude would be very small, if not negligible, despite statistical significance. At the population level, this may be particularly alarming given that currently across Europe 32 million people (nearly five million in UK) are exposed to road traffic noise >65 dB.…”

Section: Discussionmentioning

confidence: 99%

Road traffic noise and cardiovascular disease risk factors in UK Biobank

Kupcikova

Fecht

Ramakrishnan

et al. 2021

European Heart Journal

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Aims The aim of this study was to investigate the cross-sectional associations of modelled residential road traffic noise with cardiovascular disease risk factors [systolic (SBP) and diastolic blood pressure (DBP), C-reactive protein, triglycerides, glycated haemoglobin, and self-reported hypertension] in UK Biobank. Methods and results The UK Biobank recruited 502 651 individuals aged 40–69 years across the UK during 2006–10. Road traffic noise (Lden and Lnight) exposure for 2009 was estimated at baseline address using a simplified version of the Common Noise Assessment Methods model. We used multivariable linear and logistic regression models, adjusting for age, sex, body mass index (BMI), smoking, alcohol intake, area- and individual-level deprivation, season of blood draw, length of time at residence, and nitrogen dioxide (main model), in an analytical sample size of over 370 000 participants. Exposure to road-traffic Lden >65 dB[A], as compared to ≤55 dB[A], was associated with 0.77% [95% confidence interval (CI) 0.60%, 0.95%], 0.49% (95% CI 0.32%, 0.65%), 0.79% (95% CI 0.11%, 1.47%), and 0.12% (95% CI −0.04%, 0.28%) higher SBP, DBP, triglycerides, and glycated haemoglobin, respectively. Removing BMI from the main model yielded significant positive associations with all five markers with elevated percent changes. The associations with SBP or DBP did not appear to be impacted by hypertension medication while a positive association with prevalent self-reported hypertension was seen in the non-medicated group who exposed to a Lden level of 60–65 dB[A] (odds ratio 1.07, 95% CI 1.00, 1.15). Conclusion Exposure to road traffic noise >65 dB[A], independent of nitrogen dioxide, was associated with small but adverse changes in blood pressure and cardiovascular biochemistry.

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Section: Discussionmentioning

confidence: 99%

Road traffic noise and cardiovascular disease risk factors in UK Biobank

Kupcikova

Fecht

Ramakrishnan

et al. 2021

European Heart Journal

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“…Clinical biochemistry markers, including total cholesterol, HDL cholesterol, and CRP, were measured at baseline in serum samples. Full details of the biochemistry sampling, handling and quality control protocol, and assay method have been provided previously [ 21 ].…”

Section: Methodsmentioning

confidence: 99%

Polygenic risk scores in cardiovascular risk prediction: A cohort study and modelling analyses

et al. 2021

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Background Polygenic risk scores (PRSs) can stratify populations into cardiovascular disease (CVD) risk groups. We aimed to quantify the potential advantage of adding information on PRSs to conventional risk factors in the primary prevention of CVD. Methods and findings Using data from UK Biobank on 306,654 individuals without a history of CVD and not on lipid-lowering treatments (mean age [SD]: 56.0 [8.0] years; females: 57%; median follow-up: 8.1 years), we calculated measures of risk discrimination and reclassification upon addition of PRSs to risk factors in a conventional risk prediction model (i.e., age, sex, systolic blood pressure, smoking status, history of diabetes, and total and high-density lipoprotein cholesterol). We then modelled the implications of initiating guideline-recommended statin therapy in a primary care setting using incidence rates from 2.1 million individuals from the Clinical Practice Research Datalink. The C-index, a measure of risk discrimination, was 0.710 (95% CI 0.703–0.717) for a CVD prediction model containing conventional risk predictors alone. Addition of information on PRSs increased the C-index by 0.012 (95% CI 0.009–0.015), and resulted in continuous net reclassification improvements of about 10% and 12% in cases and non-cases, respectively. If a PRS were assessed in the entire UK primary care population aged 40–75 years, assuming that statin therapy would be initiated in accordance with the UK National Institute for Health and Care Excellence guidelines (i.e., for persons with a predicted risk of ≥10% and for those with certain other risk factors, such as diabetes, irrespective of their 10-year predicted risk), then it could help prevent 1 additional CVD event for approximately every 5,750 individuals screened. By contrast, targeted assessment only among people at intermediate (i.e., 5% to <10%) 10-year CVD risk could help prevent 1 additional CVD event for approximately every 340 individuals screened. Such a targeted strategy could help prevent 7% more CVD events than conventional risk prediction alone. Potential gains afforded by assessment of PRSs on top of conventional risk factors would be about 1.5-fold greater than those provided by assessment of C-reactive protein, a plasma biomarker included in some risk prediction guidelines. Potential limitations of this study include its restriction to European ancestry participants and a lack of health economic evaluation. Conclusions Our results suggest that addition of PRSs to conventional risk factors can modestly enhance prediction of first-onset CVD and could translate into population health benefits if used at scale.

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“…Hormones and SHBG were measured in blood samples collected at recruitment, using chemiluminescent immunoassays. Detailed information on the assay data has been reported elsewhere [18,19]. The coefficients of variation derived from the internal quality control data are S1.…”

Section: Hormone Assaysmentioning

confidence: 99%

Alcohol Intake and Endogenous Hormones in Pre- and Postmenopausal Women: Findings from the UK Biobank

Tin

Key

Reeves

2021

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: Alcohol intake may influence breast cancer risk in women through hormonal changes, but the evidence to date is inconclusive. We investigated cross-sectional associations between habitual alcohol intake and serum concentrations of testosterone, SHBG (sex hormone binding globulin), IGF-1 (insulin-like growth factor-1) and oestradiol (pre-menopausal women only) in UK Biobank.Methods: We included 30,557 pre-menopausal and 134,029 post-menopausal women aged between 40-69 years when recruited between 2006 and 2010. At their initial assessment visit, habitual alcohol intake was assessed using a touchscreen questionnaire, and serum hormone concentrations were assayed. Multivariable linear regression analysis was performed.Results: Per 10 g/day increment in alcohol intake, testosterone concentration was 3.9% (95% CI: 3.3%, 4.5%) higher in pre-menopausal women and 2.3% (1.8%, 2.7%) higher in post-menopausal women (p heterogeneity <0.0001); SHBG concentration was 0.7% (0.2%, 1.1%) higher in pre-menopausal women and 2.4% (2.2%, 2.6%) lower in post-menopausal women (p heterogeneity <0.0001); and IGF-1 concentration was 1.9% (1.7%, 2.1%) lower in pre-menopausal women and 0.8% (0.6%, 0.9%) lower in post-menopausal women (p heterogeneity <0.0001). In pre-menopausal women, there was no significant overall association of alcohol with oestradiol but a positive association was observed in the early and mid-luteal phases: 1.9% (95% CI: 0.2%, 3.6%) and 2.4% (95% CI: 0.7%, 4.2%) higher respectively.Conclusions: This study confirms significant but modest associations between alcohol intake and hormones, with evidence of heterogeneity by menopausal status. Impact:The findings facilitate better understanding of whether alcohol intake influences hormone concentrations, but further work is necessary to fully understand the mechanisms linking alcohol with cancer risk.

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Approaches to minimising the epidemiological impact of sources of systematic and random variation that may affect biochemistry assay data in UK Biobank

Cited by 33 publications

References 24 publications

Road traffic noise and cardiovascular disease risk factors in UK Biobank

Road traffic noise and cardiovascular disease risk factors in UK Biobank

Polygenic risk scores in cardiovascular risk prediction: A cohort study and modelling analyses

Alcohol Intake and Endogenous Hormones in Pre- and Postmenopausal Women: Findings from the UK Biobank

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