A Frailty Index for UK Biobank Participants

Williams, Dylan M; Jylhävä, Juulia; Pedersen, Nancy L.; Hägg, Sara

doi:10.1093/gerona/gly094

Cited by 93 publications

(93 citation statements)

References 23 publications

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“…A frailty index has previously been validated using baseline data from UK Biobank [ 26 ]. The frailty index approach was developed by Rockwood and Mitnitski and is a cumulative count of ‘deficits’ [ 27 , 28 ].…”

Section: Methodsmentioning

confidence: 99%

“…However, the frailty index method was developed as a standard technique which can be adapted to the deficits available in a given dataset [ 29 ]. The adaptation of the frailty index approach to UK Biobank is described in detail elsewhere [ 26 ]. Briefly, deficits should be associated with age, associated with poor health status, and be neither universal nor too rare within the target population [ 29 ].…”

Section: Methodsmentioning

confidence: 99%

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Comparison of two different frailty measurements and risk of hospitalisation or death from COVID-19: findings from UK Biobank

Petermann-Rocha

Hanlon

Gray

et al. 2020

BMC Med

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Background Frailty has been associated with worse prognosis following COVID-19 infection. While several studies have reported the association between frailty and COVID-19 mortality or length of hospital stay, there have been no community-based studies on the association between frailty and risk of severe infection. Considering that different definitions have been identified to assess frailty, this study aimed to compare the association between frailty and severe COVID-19 infection in UK Biobank using two frailty classifications: the frailty phenotype and the frailty index. Methods A total of 383,845 UK Biobank participants recruited 2006–2010 in England (211,310 [55.1%] women, baseline age 37–73 years) were included. COVID-19 test data were provided by Public Health England (available up to 28 June 2020). An adapted version of the frailty phenotype derived by Fried et al. was used to define frailty phenotype (robust, pre-frail, or frail). A previously validated frailty index was derived from 49 self-reported questionnaire items related to health, disease and disability, and mental wellbeing (robust, mild frailty, and moderate/severe frailty). Both classifications were derived from baseline data (2006–2010). Poisson regression models with robust standard errors were used to analyse the associations between both frailty classifications and severe COVID-19 infection (resulting in hospital admission or death), adjusted for sociodemographic and lifestyle factors. Results Of UK Biobank participants included, 802 were admitted to hospital with and/or died from COVID19 (323 deaths and 479 hospitalisations). After analyses were adjusted for sociodemographic and lifestyle factors, a higher risk of COVID-19 was observed for pre-frail (risk ratio (RR) 1.47 [95% CI 1.26; 1.71]) and frail (RR 2.66 [95% CI 2.04; 3.47]) individuals compared to those classified as robust using the frailty phenotype. Similar results were observed when the frailty index was used (RR mildly frail 1.46 [95% CI 1.26; 1.71] and RR moderate/severe frailty 2.43 [95% CI 1.91; 3.10]). Conclusions Frailty was associated with a higher risk of severe COVID-19 infection resulting in hospital admission or death, irrespective of how it was measured and independent of sociodemographic and lifestyle factors. Public health strategies need to consider the additional risk that COVID-19 poses in individuals with frailty, including which additional preventive measures might be required.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Comparison of two different frailty measurements and risk of hospitalisation or death from COVID-19: findings from UK Biobank

Petermann-Rocha

Hanlon

Gray

et al. 2020

BMC Med

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“…Several studies with wide age spectra have nevertheless suggested that a negative effect of increased FI on mortality could also be observed in younger adults [14,[22][23][24]. In fact, previous findings by others [22] and us [24,25] have suggested that the frailty-mortality association is relatively stronger among the young than the old. In the present study, we modeled the effect in a time-dependent manner and found that for all causes, higher FI was associated with a greater relative risk of mortality at younger ages and the associations attenuated towards the oldest ages.…”

Section: Discussionmentioning

confidence: 95%

The frailty index is a predictor of cause-specific mortality independent of familial effects from midlife onwards

Ploner

Karlsson

et al. 2018

Preprint

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Background. Frailty index (FI) is a well-established predictor of all-cause mortality, but less is known for cause-specific mortality and whether familial effects influence the associations.Furthermore, the population mortality impact of frailty remains understudied.Objectives. To estimate the predictive value of frailty for all-cause and cause-specific mortality, and to test whether the associations are time-dependent. We also assessed the proportion of deaths that are attributable to increased levels of frailty.Methods. We analyzed 42,953 participants from the Screening Across the Lifespan Twin Study (aged 41-95 years at baseline) with up to 20-years' mortality follow-up. The FI was constructed using 44 health-related items. Deaths due to cardiovascular disease (CVD), respiratory-related causes and cancer were considered in the cause-specific analysis. Generalized survival models were used in the analysis. Results.Increased FI was associated with higher risks of all-cause, CVD, and respiratory-related mortality. No significant associations were observed for cancer mortality. No attenuation of the mortality associations was found in unrelated individuals when adjusting for familial effects in twin pairs. The associations were time-dependent with relatively greater effects observed in younger ages. The proportion of deaths attributable to FI levels >0.10 were 13.0% of all-cause deaths, 14.7% of CVD deaths and 12.5% of respiratory-related deaths in men, and 12.2% of allcause deaths, 9.9% of CVD deaths and 21.9% of respiratory-related deaths in women. Conclusions.Increased FI predicts higher risks of all-cause, CVD, and respiratory-related mortality independent of familial effects. Increased FI levels have a significant population mortality impact in both men and women.

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“…We applied the algorithm proposed by Williams et al to compute a FI for each participant. 21 Briefly, 49 self-reported questionnaire variables related to health, disease, disability, and mental wellbeing were extracted and coded into binary (0 or 1) or ordinal variables (values ranging from 0 to 1). For each UKB participant, FI was computed from the sum of the observations across these 49 variables and divided by 49 and expressed as a percent.…”

Section: Methodsmentioning

confidence: 99%

Genetically Increased Telomere Length and Aging-related Physical and Cognitive Traits in the UK Biobank

Demanelis

Lin

2019

Preprint

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Background: Telomere length (TL) shortens over time in most human cell types and is a potential biomarker aging. However, the causal impact of TL on physical and cognitive phenotypes that decline with age has not been extensively examined. Using a Mendelian randomization (MR) approach, we utilized genetically increased TL (GI-TL) to estimate the impact of TL on aging-related traits among UK Biobank (UKB) participants. Methods: We manually curated >50 aging-related traits from UKB and restricted to unrelated participants of British ancestry (n=337,522). We estimated GI-TL as a linear combination of nine TL-associated SNPs, each weighted by its previously-reported association with leukocyte TL. Regression models were used to assess the associations between GI-TL and each trait. We obtained MR estimates using the two-sample inverse variance weighted (IVW) approach. Results: We identified 5 age-related traits associated with GI-TL (Bonferroni-corrected threshold p<0.001): pulse pressure (PP) (p=5.2x10 -14 ), systolic blood pressure (SBP) (p=2.9x10 -15 ), diastolic blood pressure (DBP) (p=5.5x10 -6 ), forced expiratory volume (FEV1) (p= p=0.0001), and forced vital capacity (FVC) (p=3.8x10 -6 ). Under MR assumptions, one standard deviation increase in TL (~1200 base pairs) increased PP, SBP, and DBP by 1.5, 2.3, and 0.8 mmHg, respectively, while FEV1 and FVC increased by 34.7 and 52.2 mL, respectively. The observed associations appear unlikely to be due to selection bias based on analyses including inverse probability weights and analyses of simulated data. Conclusions: These findings suggest that longer TL increases pulmonary function and blood pressure traits. Further research is necessary to evaluate TL in cardiovascular and pulmonary age-related decline. KEY MESSAGES:• Telomere length (TL) is a potential biomarker and cause of aging, however, the causal relationship between TL and aging-related traits has not been thoroughly examined using a Mendelian randomization (MR) approach. • We evaluated genetically increased TL (GI-TL) and its association with over 50 agingrelated traits in the UK Biobank cohort using regression models and MR approaches. • Pulmonary function (FEV1 and FVC) and blood pressure (SBP, DBP, and PP) traits were positively associated with GI-TL in the expected and unexpected direction, respectively. • Using inverse probability weights to account for the non-representativeness of the UKB, our observed associations for GI-TL with blood pressure traits and pulmonary function persisted. • Using simulated data to examine study selection as a potential source of collider bias, we concluded that selection bias was unlikely to explain the observed associations.

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A Frailty Index for UK Biobank Participants

Abstract: The FI is a valid measure of frailty in UK Biobank. The cohort's data are open access for researchers to use, and we provide script for deriving this tool to facilitate future studies on frailty.

Cited by 93 publications

References 23 publications

Comparison of two different frailty measurements and risk of hospitalisation or death from COVID-19: findings from UK Biobank

Comparison of two different frailty measurements and risk of hospitalisation or death from COVID-19: findings from UK Biobank

The frailty index is a predictor of cause-specific mortality independent of familial effects from midlife onwards

Genetically Increased Telomere Length and Aging-related Physical and Cognitive Traits in the UK Biobank

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