P1-032: RELATIVE IMPACTS OF AGING AND MODIFIABLE RISK FACTORS FOR DEMENTIA ON BRAIN VOLUMES IN THE UK BIOBANK COHORT

Abstract Background: To inform targeted preventive strategies of dementia, systematic investigation in its age- and sex-specific modifiable risk factor profiles in the general adult population is warranted.Methods: We used data of 372,867 adults free from dementia at baseline (2006-2010) in the UK Biobank, and followed them up until March 2021. We assigned participants into five groups according to their age and into two groups according to their sex. We estimated the age- and sex-specific hazard ratios (HRs) using Cox proportional hazard models and calculated the corresponding population attributable fractions (PAFs) for dementia attributable to three major categories of modifiable risk factors, including socioeconomic (low education level, high Townsend deprivation index), lifestyle (non-moderate alcohol intake, current smoking, suboptimal diet, non-regular physical exercise, and sleep duration <=6 or >=8 hrs/d), and health condition (hypertension, diabetes, cardiovascular diseases, and depressive symptom) risk factors.Findings: During 4,338,030 person-years of follow-up, 113, 146, 360, 1,087, and 2,002 of participants across five increasing age groups (40-<50, 50-<55, 55-<60, 60-<65, or >=65 y), respectively, were newly diagnosed with dementia. Five out of eleven modifiable risk factors showed significantly stronger associations with dementia among younger adults than in relatively older adults (P-interactions < 0.05), including non-moderate alcohol intake (HR [95% confidence interval, CI]=1.90 [1.35, 2.68] for participants 50-<55 y vs. 1.22 [1.11, 1.35] for participants > 65 y), suboptimal diet (1.86 [1.26, 2.74] for participants 40-< 50 y vs. 0.96 [0.86, 1.06] for participants > 65 y), hypertension (1.52 [0.96, 2.42] vs. 1.08 [0.99, 1.19]), CVD (4.20 [2.15, 8.22] vs. 1.64 [1.45, 1.85]), and diabetes (3.09 [1.60, 6.00] vs. 1.73 [1.51, 2.00]). We observed no significant difference in dementia risk factor profiles between women and men. Dementia cases attributable to three categories of risk factors all decreased with age, with the PAFs (95% CI) for sociodemographic, lifestyle, and health condition risk factors being 52.56% (22.98%, 82.15%), 46.57% (8.08%, 85.06%), and 35.42% (24.09%, 46.75%) for participants aged 40-<50 y, and 12.29% (3.82%, 20.75%), 13.01% (2.53%, 23.49%), and 15.85% (11.81%, 19.90%) for those over 65 y.Interpretation: This study identified stronger association and greater attributable risk of several modifiable risk factors for dementia among younger adults, underscoring the importance of preventive strategies from an earlier age across adult life course to reduce the risk of dementia.

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699 Sleep Health Traits and COVID-19: Mortality Risk from the UK Biobank

SLEEP ◽

10.1093/sleep/zsab072.697 ◽

2021 ◽

Vol 44 (Supplement_2) ◽

pp. A273-A273

Author(s):

Xi Zheng ◽

Ma Cherrysse Ulsa ◽

Peng Li ◽

Lei Gao ◽

Kun Hu

Keyword(s):

Risk Factors ◽

Sleep Apnea ◽

Sleep Duration ◽

Sex Education ◽

Mortality Risk ◽

Self Report ◽

Severe Illness ◽

Uk Biobank ◽

Sleep Health ◽

The Uk

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 (>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.

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RISK LOCI IDENTIFICATION OF NOVEL GENETIC RISK FACTORS FOR ATRIAL SEPTAL DEFECT USING THE UK BIOBANK

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(21)01838-6 ◽

2021 ◽

Vol 77 (18) ◽

pp. 479

Author(s):

Alex Gyftopoulos ◽

Yi-Ju Chen ◽

James A. Perry ◽

Charles C. Hong

Keyword(s):

Risk Factors ◽

Atrial Septal Defect ◽

Genetic Risk ◽

Septal Defect ◽

Genetic Risk Factors ◽

Uk Biobank ◽

The Uk

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Sex differences in the association between major cardiovascular risk factors in midlife and dementia: a cohort study using data from the UK Biobank

BMC Medicine ◽

10.1186/s12916-021-01980-z ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Jessica Gong ◽

Katie Harris ◽

Sanne A. E. Peters ◽

Mark Woodward

Keyword(s):

Risk Factors ◽

Blood Pressure ◽

Sex Differences ◽

Cardiovascular Risk ◽

Cardiovascular Risk Factors ◽

Sex Difference ◽

Incidence Rates ◽

Cox Proportional Hazards ◽

Uk Biobank ◽

The Uk

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.

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Variation of cardiac magnetic resonance radiomics features by age and sex in healthy participants from the UK Biobank

European Heart Journal ◽

10.1093/ehjci/ehaa946.0197 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

Z Raisi-Estabragh ◽

A Jaggi ◽

N Aung ◽

S Neubauer ◽

S Piechnik ◽

...

Keyword(s):

Risk Factors ◽

Cardiac Magnetic Resonance ◽

Age Groups ◽

Texture Features ◽

Funding Source ◽

Uk Biobank ◽

Men And Women ◽

The Uk ◽

Age And Sex ◽

Apparently Healthy

Abstract Introduction Cardiac magnetic resonance (CMR) radiomics use voxel-level data to derive quantitative indices of myocardial tissue texture, which may provide complementary risk information to traditional CMR measures. Purpose In this first stage of our work, establishing the performance characteristics of CMR radiomics in relation to disease outcomes, we aimed to elucidate differences in radiomic features by sex and age in apparently healthy adults. Methods We defined a healthy cohort from the first 5,065 individuals completing the UK Biobank Imaging Enhancement, limiting to white Caucasian ethnicity, and excluding those with major co-morbidities, or cardiovascular risk factors/symptoms. We created evenly distributed age groups: 45–54 years, 55–64 years, 65–74 years. Radiomics features were extracted from left ventricle segmentations, with normalisation to body surface area. We compared mean values of individual features between the sexes, stratified by age and separately between the oldest and youngest age groups for each sex. Results We studied 657 (309 men, 358 women) healthy individuals. There were significant differences between radiomics features of men and women. Different features appeared more important at different age groups. For instance, in the youngest age group “end-systolic coarseness” showed greatest difference between men and women, whilst “end-diastolic run percentage” and “end-diastolic high grey level emphasis” showed most variation in the oldest and middle age groups. In the oldest age groups, differences between men and women were most predominant in the texture features, whilst in the younger groups a mixture of shape and texture differences were observed. We demonstrate significant variation between radiomics features by age, these differences are exclusively in texture features with different features implicated in men and women (“end-diastolic mean intensity” in women, “end-systolic sum entropy in men”). Conclusions There are significant age and sex differences in CMR radiomics features of apparently healthy adults, demonstrating alterations in myocardial architecture not appreciated by conventional indices. In younger ages, shape and texture differences are observed, whilst in older ages texture differences dominate. Furthermore, texture features are the most different features between the youngest and oldest hearts. We provide proof-of-concept data indicating CMR radiomics has discriminatory value with regard to two characteristics strongly linked to cardiovascular outcomes. We will next elucidate relationships between CMR radiomics, cardiac risk factors, and clinical outcomes, establishing predictive value incremental to existing measures. Funding Acknowledgement Type of funding source: Other. Main funding source(s): European Union's Horizon 2020 research and innovation programme (825903),British Heart Foundation Clinical Research Training Fellowship (FS/17/81/33318)

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Polygenic risk for schizophrenia and subcortical brain anatomy in the UK Biobank cohort

Translational Psychiatry ◽

10.1038/s41398-020-00940-0 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Steluta Grama ◽

Isabella Willcocks ◽

John J. Hubert ◽

Antonio F. Pardiñas ◽

Sophie E. Legge ◽

...

Keyword(s):

Multiple Testing ◽

Specific Gene ◽

Whole Genome ◽

Uk Biobank ◽

Abnormal Behaviour ◽

Brain Volumes ◽

Polygenic Risk ◽

Subcortical Brain ◽

Gene Sets ◽

The Uk

Abstract Research has shown differences in subcortical brain volumes between participants with schizophrenia and healthy controls. However, none of these differences have been found to associate with schizophrenia polygenic risk. Here, in a large sample (n = 14,701) of unaffected participants from the UK Biobank, we test whether schizophrenia polygenic risk scores (PRS) limited to specific gene-sets predict subcortical brain volumes. We compare associations with schizophrenia PRS at the whole genome level (‘genomic’, including all SNPs associated with the disorder at a p-value threshold < 0.05) with ‘genic’ PRS (based on SNPs in the vicinity of known genes), ‘intergenic’ PRS (based on the remaining SNPs), and genic PRS limited to SNPs within 7 gene-sets previously found to be enriched for genetic association with schizophrenia (‘abnormal behaviour,’ ‘abnormal long-term potentiation,’ ‘abnormal nervous system electrophysiology,’ ‘FMRP targets,’ ‘5HT2C channels,’ ‘CaV2 channels’ and ‘loss-of-function intolerant genes’). We observe a negative association between the ‘abnormal behaviour’ gene-set PRS and volume of the right thalamus that survived correction for multiple testing (ß = −0.031, pFDR = 0.005) and was robust to different schizophrenia PRS p-value thresholds. In contrast, the only association with genomic PRS surviving correction for multiple testing was for right pallidum, which was observed using a schizophrenia PRS p-value threshold < 0.01 (ß = −0.032, p = 0.0003, pFDR = 0.02), but not when using other PRS P-value thresholds. We conclude that schizophrenia PRS limited to functional gene sets may provide a better means of capturing differences in subcortical brain volume than whole genome PRS approaches.

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Genetic variation in the SIM1 locus is associated with erectile dysfunction

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1809872115 ◽

2018 ◽

Vol 115 (43) ◽

pp. 11018-11023 ◽

Cited By ~ 14

Author(s):

Eric Jorgenson ◽

Navneet Matharu ◽

Melody R. Palmer ◽

Jie Yin ◽

Jun Shan ◽

...

Keyword(s):

Risk Factors ◽

Erectile Dysfunction ◽

Sexual Function ◽

Odds Ratio ◽

Large Scale ◽

Genome Wide Association Study ◽

Adult Health ◽

Uk Biobank ◽

Melanocortin System ◽

The Uk

Erectile dysfunction affects millions of men worldwide. Twin studies support the role of genetic risk factors underlying erectile dysfunction, but no specific genetic variants have been identified. We conducted a large-scale genome-wide association study of erectile dysfunction in 36,649 men in the multiethnic Kaiser Permanente Northern California Genetic Epidemiology Research in Adult Health and Aging cohort. We also undertook replication analyses in 222,358 men from the UK Biobank. In the discovery cohort, we identified a single locus (rs17185536-T) on chromosome 6 near the single-minded family basic helix-loop-helix transcription factor 1 (SIM1) gene that was significantly associated with the risk of erectile dysfunction (odds ratio = 1.26, P = 3.4 × 10−25). The association replicated in the UK Biobank sample (odds ratio = 1.25, P = 6.8 × 10−14), and the effect is independent of known erectile dysfunction risk factors, including body mass index (BMI). The risk locus resides on the same topologically associating domain as SIM1 and interacts with the SIM1 promoter, and the rs17185536-T risk allele showed differential enhancer activity. SIM1 is part of the leptin–melanocortin system, which has an established role in body weight homeostasis and sexual function. Because the variants associated with erectile dysfunction are not associated with differences in BMI, our findings suggest a mechanism that is specific to sexual function.

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The impact of cardiovascular risk factors on cardiac structure and function: Insights from the UK Biobank imaging enhancement study

PLoS ONE ◽

10.1371/journal.pone.0185114 ◽

2017 ◽

Vol 12 (10) ◽

pp. e0185114 ◽

Cited By ~ 24

Author(s):

Steffen E. Petersen ◽

Mihir M. Sanghvi ◽

Nay Aung ◽

Jackie A. Cooper ◽

José Miguel Paiva ◽

...

Keyword(s):

Risk Factors ◽

Cardiovascular Risk ◽

Cardiovascular Risk Factors ◽

Structure And Function ◽

Cardiac Structure ◽

Uk Biobank ◽

Cardiac Structure And Function ◽

The Uk ◽

And Function ◽

The Impact

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Baseline cardiometabolic profiles and SARS-CoV-2 infection in the UK Biobank

PLoS ONE ◽

10.1371/journal.pone.0248602 ◽

2021 ◽

Vol 16 (4) ◽

pp. e0248602 ◽

Cited By ~ 1

Author(s):

Ryan J. Scalsky ◽

Yi-Ju Chen ◽

Karan Desai ◽

Jeffery R. O’Connell ◽

James A. Perry ◽

...

Keyword(s):

Risk Factors ◽

Type Ii Diabetes ◽

Cardiometabolic Risk ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Lipoprotein Cholesterol ◽

Type Ii ◽

Uk Biobank ◽

The Uk ◽

The Impact

Background SARS-CoV-2 is a rapidly spreading coronavirus responsible for the Covid-19 pandemic, which is characterized by severe respiratory infection. Many factors have been identified as risk factors for SARS-CoV-2, with much early attention being paid to body mass index (BMI), which is a well-known cardiometabolic risk factor. Objective This study seeks to examine the impact of additional baseline cardiometabolic risk factors including high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), Apolipoprotein A-I (ApoA-I), Apolipoprotein B (ApoB), triglycerides, hemoglobin A1c (HbA1c) and diabetes on the odds of testing positive for SARS-CoV-2 in UK Biobank (UKB) study participants. Methods We examined the effect of BMI, lipid profiles, diabetes and alcohol intake on the odds of testing positive for SARS-Cov-2 among 9,005 UKB participants tested for SARS-CoV-2 from March 16 through July 14, 2020. Odds ratios and 95% confidence intervals were computed using logistic regression adjusted for age, sex and ancestry. Results Higher BMI, Type II diabetes and HbA1c were associated with increased SARS-CoV-2 odds (p < 0.05) while HDL-C and ApoA-I were associated with decreased odds (p < 0.001). Though the effect of BMI, Type II diabetes and HbA1c were eliminated when HDL-C was controlled, the effect of HDL-C remained significant when BMI was controlled for. LDL-C, ApoB and triglyceride levels were not found to be significantly associated with increased odds. Conclusion Elevated HDL-C and ApoA-I levels were associated with reduced odds of testing positive for SARS-CoV-2, while higher BMI, type II diabetes and HbA1c were associated with increased odds. The effects of BMI, type II diabetes and HbA1c levels were no longer significant after controlling for HDL-C, suggesting that these effects may be mediated in part through regulation of HDL-C levels. In summary, our study suggests that baseline HDL-C level may be useful for stratifying SARS-CoV-2 infection risk and corroborates the emerging picture that HDL-C may confer protection against sepsis in general and SARS-CoV-2 in particular.

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