scholarly journals Pleiotropic associations of heterozygosity for the SERPINA1 Z allele in the UK Biobank

2021 ◽  
pp. 00049-2021
Author(s):  
Katherine A. Fawcett ◽  
Kijoung Song ◽  
Guoqing Qian ◽  
Aliki-Eleni Farmaki ◽  
Richard Packer ◽  
...  
Keyword(s):  
Lung Function ◽  
Disease Risk ◽  
Large Population ◽  
Rare Condition ◽  
Forced Expiratory Volume ◽  
Uk Biobank ◽  
Mineral Density ◽  
Increased Risk ◽  
The Uk ◽  
Reduced Risk

Homozygosity for the SERPINA1 Z allele causes alpha-1 antitrypsin deficiency, a rare condition that can cause lung and liver disease. However, the effects of Z allele heterozygosity on non-respiratory phenotypes, and on lung function in the general population, remain unclear.We conducted a large population-based study to determine Z allele effects on >2400 phenotypes in UK Biobank (N>303 353).Z allele heterozygosity was strongly associated with increased height (β=1.02 cm, p=3.91×10−68), and with other non-respiratory phenotypes including increased risk of gall bladder disease, reduced risk of heart disease and lower blood pressure, reduced risk of osteoarthritis and reduced bone mineral density, increased risk of headache and enlarged prostate, as well as with blood biomarkers of liver function. Heterozygosity was associated with higher height-adjusted forced expiratory volume in 1 s (FEV1) (β=19.36 mL, p=9.21×10−4) and FEV1/forced vital capacity (FEV1/FVC) (β=0.0031, p=1.22×10−5) in non-smokers, whereas in smokers this protective effect was abolished. Furthermore, we show for the first time that sex modifies the association of the Z allele on lung function.We conclude that Z allele heterozygosity and homozygosity exhibit opposing effects on lung function in the UK population, and that these associations are modified by smoking and sex. In exploratory analyses, heterozygosity for the Z allele also showed pleiotropic associations with non-respiratory health-related traits and disease risk.

scholarly journals Pleiotropic effects of heterozygosity for the SERPINA1 Z allele in the UK Biobank

2020 ◽  
Author(s):  
Katherine A Fawcett ◽  
Kijoung Song ◽  
Guoqing Qian ◽  
Aliki-Eleni Farmaki ◽  
Richard Packer ◽  
...  
Keyword(s):  
Lung Function ◽  
Rare Condition ◽  
Population Based ◽  
Uk Biobank ◽  
Mineral Density ◽  
Increased Risk ◽  
Alpha 1 Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin ◽  
The Uk ◽  
Reduced Risk

Homozygosity for the SERPINA1 Z allele causes alpha-1 antitrypsin deficiency, a rare condition that can cause lung and liver disease. However, the effects of Z allele heterozygosity on non-respiratory phenotypes, and on lung function in the general population, remain unclear. We conducted the largest population-based study to date to determine Z allele effects on >2,400 phenotypes using the UK Biobank study (N>303,353). We detected strong associations between heterozygosity and non-respiratory phenotypes including increased height, increased risk of gall bladder disease, reduced risk of heart disease and lower blood pressure, reduced risk of osteoarthritis and reduced bone mineral density, increased risk of headache and enlarged prostate, as well as with blood biomarkers of liver function. Heterozygosity was associated with higher lung function in non-smokers, but smoking appears to abolish this protective effect. Individuals heterozygous for the Z allele may therefore have altered risk of smoking-induced lung disease and other, non-respiratory conditions.

scholarly journals Is asthma associated with COVID-19 infection? A UK Biobank analysis

2021 ◽  
pp. 00309-2021
Author(s):  
Caroline J. Lodge ◽  
Alice Doherty ◽  
Dinh Bui ◽  
Raisa Cassim ◽  
Adrian J. Lowe ◽  
...  
Keyword(s):  
Lung Function ◽  
Early Onset ◽  
Age At Onset ◽  
Forced Expiratory Volume ◽  
Normal Weight ◽  
Asthma Medication ◽  
Positive Test ◽  
Uk Biobank ◽  
Increased Risk ◽  
Health Related

BackgroundThe relationship between asthma and COVID-19 risk is not clear and may be influenced by level of airway obstruction, asthma medication, and known COVID risk factors. We aimed to investigate COVID-19 risk in people with asthma.MethodsWe used UK Biobank data from all participants tested for SARS-CoV-2 (n=107 412 (17 979 test positive)). Baseline questions at baseline defined ever asthma and asthma medications. Baseline Forced Expiratory Volume in the first second (FEV1) was categorized into quartiles. Logistic regression modelled relationships between asthma, and asthma categories (age at onset, medications, FEV1 quartiles), and risk of SARS-CoV-2 positive test. We investigated modification by sex, ethnic group, smoking, and BMI.ResultsThere was a reduced risk of a positive test associated with with early-onset asthma (<13 years), (OR 0.91(95% CI 0.84, 0.99). This was found for early-onset asthmatics in males (OR 0·87 [95% CI: 0·78, 0·98]), non-smokers (0·87 [0·78, 0·98]), overweight/obese (0.85 [0.77, 0.93]), and non-Black participants (0·90 [0·82, 0.98]). There was increased risk amongst early onset asthmatics in the highest compared to lowest quartile of lung function (1.44 [1.05, 1.72]).ConclusionAmongst males, non-smokers, overweight/obese, and non-Black participants, having early-onset asthma was associated with lower risk of a SARS-CoV-2 positive test. We found no evidence of a protective effect from asthma medication. Early-onset asthmatics of normal weight and with better lung function may have lifestyle differences placing them at higher risk. Further research is needed to elucidate the contribution of asthma pathophysiology and different health-related behaviour, across population groups, to the observed risks.

scholarly journals Lifetime depression and age-related changes in body composition, cardiovascular function, grip strength and lung function: sex-specific analyses in the UK Biobank

BJPsych Open ◽  
2021 ◽  
Vol 7 (S1) ◽  
pp. S44-S44
Author(s):  
Julian Mutz ◽  
Cathryn M Lewis
Keyword(s):  
Body Composition ◽  
Lung Function ◽  
Cardiovascular Function ◽  
Healthy Controls ◽  
Physiological Measures ◽  
Uk Biobank ◽  
Mineral Density ◽  
Age Related ◽  
The Uk ◽  
Age Related Changes

AimsIndividuals with mental disorders, on average, die prematurely, have higher levels of physical comorbidities and may experience accelerated ageing. In individuals with lifetime depression and healthy controls, we examined associations between age and multiple physiological measures.MethodThe UK Biobank study recruited >500,000 participants, aged 37–73 years, between 2006–2010. Generalised additive models were used to examine associations between age and grip strength, cardiovascular function, body composition, lung function and bone mineral density. Analyses were conducted separately in males and females with depression compared to healthy controls.ResultAnalytical samples included up to 342,393 adults (mean age = 55.87 years; 52.61% females). We found statistically significant differences between individuals with depression and healthy controls for most physiological measures, with standardised mean differences between -0.145 and 0.156. There was some evidence that age-related changes in body composition, cardiovascular function, lung function and heel bone mineral density followed different trajectories in individuals with depression. These differences did not uniformly narrow or widen with age. For example, BMI in female cases was 1.1 kg/m2 higher at age 40 and this difference narrowed to 0.4 kg/m2 at age 70. In males, systolic blood pressure was 1 mmHg lower in cases at age 45 and this difference widened to 2.5 mmHg at age 65.ConclusionIndividuals with depression differed from healthy controls across a broad range of physiological measures. Differences in ageing trajectories differed by sex and were not uniform across physiological measures, with evidence of both age-related narrowing and widening of case-control differences.

scholarly journals Race, Socioeconomic Deprivation, and Hospitalization for COVID-19 in English participants of a National Biobank

2020 ◽  
Author(s):  
Aniruddh P. Patel ◽  
Manish D. Paranjpe ◽  
Nina P. Kathiresan ◽  
Manuel A. Rivas ◽  
Amit V. Khera
Keyword(s):  
Household Income ◽  
Odds Ratio ◽  
Large Population ◽  
Socioeconomic Deprivation ◽  
Composite Measure ◽  
Uk Biobank ◽  
Hospitalization Rates ◽  
Increased Risk ◽  
The Uk ◽  
Biologic Factors

Preliminary reports suggest that the Coronavirus Disease 2019 (COVIDâ^’19) pandemic has led to disproportionate morbidity and mortality among historically disadvantaged populations. The extent to which these disparities are related to socioeconomic versus biologic factors is largely unknown. We investigate the racial and socioeconomic associations of COVIDâ^’19 hospitalization among 418,794 participants of the UK Biobank, of whom 549 (0.13%) had been hospitalized. Both black participants (odds ratio 3.4; 95%CI 2.4â^’4.9) and Asian participants (odds ratio 2.1; 95%CI 1.5â^’3.2) were at substantially increased risk as compared to white participants. We further observed a striking gradient in COVIDâ^’19 hospitalization rates according to the Townsend Deprivation Index â^’ a composite measure of socioeconomic deprivation â^’ and household income. Adjusting for such factors led to only modest attenuation of the increased risk in black participants, adjusted odds ratio 3.1 (95%CI 2.0â^’4.8). These observations confirm and extend earlier preliminary and lay press reports of higher morbidity in non-white individuals in the context of a large population of participants in a national biobank. The extent to which this increased risk relates to variation in pre-existing comorbidities, differences in testing or hospitalization patterns, or additional disparities in social determinants of health warrants further study.

scholarly journals Lower lung function associates with cessation of menstruation: UK Biobank data

2016 ◽  
Vol 48 (5) ◽  
pp. 1288-1297 ◽  
Author(s):  
André F.S. Amaral ◽  
David P. Strachan ◽  
Francisco Gómez Real ◽  
Peter G.J. Burney ◽  
Deborah L. Jarvis
Keyword(s):  
Lung Function ◽  
Odds Ratio ◽  
Adjusted Odds Ratio ◽  
Vital Capacity ◽  
Airflow Obstruction ◽  
Forced Expiratory Volume ◽  
Uk Biobank ◽  
Lower Lung ◽  
The Uk ◽  
Lower Limit Of Normal

Little is known about the effect of cessation of menstruation on lung function. The aims of the study were to examine the association of lung function with natural and surgical cessation of menstruation, and assess whether lower lung function is associated with earlier age at cessation of menstruation.The study was performed in 141 076 women from the UK Biobank, who had provided acceptable and reproducible spirometry measurements and information on menstrual status. The associations of lung function (forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), spirometric restriction (FVC < lower limit of normal (LLN)), airflow obstruction (FEV1/FVC <LLN)) with cessation of menstruation and age at cessation of menstruation were assessed using regression analysis.Women who had natural cessation of menstruation showed a lower FVC (−42 mL; 95% CI −53– −30) and FEV1 (−34 mL; 95% CI −43– −24) and higher risk of spirometric restriction (adjusted odds ratio 1.27; 95% CI 1.18–1.37) than women still menstruating. These associations were stronger in women who had had a hysterectomy and/or oophorectomy. The earlier the natural cessation of menstruation, the lower the lung function. There was no clear association of lung function with age at hysterectomy and/or oophorectomy. Airflow obstruction was not associated with cessation of menstruation.Lower lung function associates with cessation of menstruation, especially if it occurs early in life.

scholarly journals Machine Learning Prediction of Biomarkers from SNPs and of Disease Risk from Biomarkers in the UK Biobank

Genes ◽  
2021 ◽  
Vol 12 (7) ◽  
pp. 991
Author(s):  
Erik Widen ◽  
Timothy G. Raben ◽  
Louis Lello ◽  
Stephen D. H. Hsu
Keyword(s):  
Disease Risk ◽  
Smoking Status ◽  
Glycated Haemoglobin ◽  
European Ancestry ◽  
Risk Scores ◽  
Common Disease ◽  
Atherosclerotic Cardiovascular Disease ◽  
Uk Biobank ◽  
Lipoprotein A ◽  
The Uk

We use UK Biobank data to train predictors for 65 blood and urine markers such as HDL, LDL, lipoprotein A, glycated haemoglobin, etc. from SNP genotype. For example, our Polygenic Score (PGS) predictor correlates ∼0.76 with lipoprotein A level, which is highly heritable and an independent risk factor for heart disease. This may be the most accurate genomic prediction of a quantitative trait that has yet been produced (specifically, for European ancestry groups). We also train predictors of common disease risk using blood and urine biomarkers alone (no DNA information); we call these predictors biomarker risk scores, BMRS. Individuals who are at high risk (e.g., odds ratio of >5× population average) can be identified for conditions such as coronary artery disease (AUC∼0.75), diabetes (AUC∼0.95), hypertension, liver and kidney problems, and cancer using biomarkers alone. Our atherosclerotic cardiovascular disease (ASCVD) predictor uses ∼10 biomarkers and performs in UKB evaluation as well as or better than the American College of Cardiology ASCVD Risk Estimator, which uses quite different inputs (age, diagnostic history, BMI, smoking status, statin usage, etc.). We compare polygenic risk scores (risk conditional on genotype: PRS) for common diseases to the risk predictors which result from the concatenation of learned functions BMRS and PGS, i.e., applying the BMRS predictors to the PGS output.

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.

Persistent airflow obstruction in inner-city children with asthma

2021 ◽  
Vol 42 (4) ◽  
pp. 310-316
Author(s):  
Kenny Y. Kwong ◽  
Yang Z. Lu ◽  
Emilio Jauregui ◽  
Lyne Scott
Keyword(s):  
Lung Function ◽  
Inner City ◽  
Airway Remodeling ◽  
Airflow Obstruction ◽  
Later Life ◽  
Forced Expiratory Volume ◽  
Initial Visit ◽  
Asthma Care ◽  
Increased Risk ◽  
Children With Asthma

Background: Airway remodeling has been shown to be persistent in patients with asthma despite treatment with controller medications. Patients with early airflow obstruction may continue to experience poor lung function despite treatment. Objectives: To determine whether early airflow obstruction in inner-city children with asthma persists despite guideline-based asthma care. Methods: In a retrospective study that used a cohort of inner-city children with asthma treated by using an asthma-specific disease management system, the patients were stratified into “low” or “high” lung function groups at the time of the initial visit (high, forced expiratory volume in the first second of expiration [FEV1] % predicted and FEV1/forced vital capacity [FVC] ≥ 80%; and low, FEV1% predicted and FEV1/FVC < 80%). These patients then received National Heart, Lung, and Blood Institute guideline‐based asthma treatment at regular follow-up intervals with spirometry performed at these visits as part of regular care. FEV1% predicted and FEV1/FVC were followed up for up to 10 years for both the high and low cohorts. Results: Over 10 years, the patients initially in the “high” group maintained FEV1% predicted and FEV1/FVC at values similar to the initial visit (94 to 96% and 87 to 89%, respectively), whereas those in the low group had only slight increases of FEV1% predicted and FEV1/FVC over the same time (77 to 82% and 78 to 82%, respectively). Low FEV1% predicted and FEV1/FVC at the time of the first visit was significantly associated with an increased risk of low values of these lung functions over the next 3‐5 years despite treatment. African American ethnicity and male gender were also associated with lower lung function over time. Conclusion: Early airflow obstruction in inner city children asthma is associated with poor lung function in later life despite guideline-based asthma care. Current asthma therapy may not affect pathways and leads to airway remodeling in children with asthma.

scholarly journals Polygenic risk for schizophrenia and season of birth within the UK Biobank cohort

2018 ◽  
Vol 49 (15) ◽  
pp. 2499-2504 ◽  
Author(s):  
Valentina Escott-Price ◽  
Daniel J. Smith ◽  
Kimberley Kendall ◽  
Joey Ward ◽  
George Kirov ◽  
...  
Keyword(s):  
Environmental Exposure ◽  
Copy Number Variants ◽  
Season Of Birth ◽  
Uk Biobank ◽  
Month Of Birth ◽  
Risk Alleles ◽  
Gene Environment ◽  
Increased Risk ◽  
The Uk ◽  
Pathogenic Process

AbstractBackgroundThere is strong evidence that people born in winter and in spring have a small increased risk of schizophrenia. As this ‘season of birth’ effect underpins some of the most influential hypotheses concerning potentially modifiable risk exposures, it is important to exclude other possible explanations for the phenomenon.MethodsHere we sought to determine whether the season of birth effect reflects gene-environment confounding rather than a pathogenic process indexing environmental exposure. We directly measured, in 136 538 participants from the UK Biobank (UKBB), the burdens of common schizophrenia risk alleles and of copy number variants known to increase the risk for the disorder, and tested whether these were correlated with a season of birth.ResultsNeither genetic measure was associated with season or month of birth within the UKBB sample.ConclusionsAs our study was highly powered to detect small effects, we conclude that the season of birth effect in schizophrenia reflects a true pathogenic effect of environmental exposure.

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