scholarly journals Reproductive Factors and the Risk of Incident Dementia: Results From the UK Biobank

2021 ◽  
Author(s):  
Jessica Gong ◽  
Katie Harris ◽  
Sanne A E Peters ◽  
Mark Woodward
Keyword(s):  
Smoking Status ◽  
Hormone Replacement ◽  
Reproductive Factors ◽  
Uk Biobank ◽  
Oral Contraceptive Pills ◽  
Number Of Children ◽  
Estrogen Exposure ◽  
Contraceptive Pills ◽  
Endogenous Estrogen ◽  
The Uk

Abstract Background: To examine the risk of incident all-cause dementia associated with reproductive factors in women, and the number of children in both sexes; and whether the effects vary by age, socioeconomic status (SES), smoking status and body mass index in the UK Biobank.Methods: A total of 273,265 women and 228,966 men without prevalent dementia from the UK Biobank were included in the analyses. Cox proportional hazard regressions estimated hazard ratios (HRs) for reproductive factors with incident all-cause dementia.Results: Over a median of 11.3 years follow-up, 1,680 dementia were recorded in women and 2,021 in men. Adjusted HRs (95% confidence intervals (CIs)) for dementia were 1.20 (1.08, 1.35) for menarche <12 years, and 1.24 (1.10, 1.39) for menarche ≥15 years compared to 13 years; 0.86 (0.74, 1.00) for ever been pregnant; 0.80 (0.69, 0.93) for each abortion; 1.29 (1.12, 1.49) for menopause at <47 compared to 50 years; 1.13 (1.01, 1.27) for hysterectomy; 0.80 (0.72, 0.90) for oral contraceptive pills use; and 1.56 (1.40, 1.73) for hormone replacement therapy (HRT) use. The U-shaped associations between the number of children and the risk of dementia were similar for both sexes. There was evidence for early (natural and artificial) menopause, and a greater number of children were associated with a higher risk of dementia among women of relatively lower SES only.Conclusions: Shorter cumulative endogenous estrogen exposure in women is associated with higher dementia risk, although female biological factors involved in childbearing are unlikely to account for risk variation.

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 Hormonal and reproductive factors and risk of upper gastrointestinal cancers in men: A prospective cohort study within the UK Biobank

2018 ◽  
Vol 143 (4) ◽  
pp. 831-841
Author(s):  
Úna C. Mc Menamin ◽  
Andrew T. Kunzmann ◽  
Michael B. Cook ◽  
Brian T. Johnston ◽  
Liam J. Murray ◽  
...  
Keyword(s):  
Cohort Study ◽  
Prospective Cohort Study ◽  
Prospective Cohort ◽  
Reproductive Factors ◽  
Uk Biobank ◽  
Gastrointestinal Cancers ◽  
The Uk ◽  
Upper Gastrointestinal

Relationship between Reproductive Exposures and Age-Related Cataract in Women

2007 ◽  
Vol 19 (2) ◽  
pp. 23-28 ◽  
Author(s):  
N.H. Noran ◽  
N. Salleh ◽  
M. Zahari
Keyword(s):  
Protective Factor ◽  
Outcome Measurement ◽  
Hormone Replacement ◽  
Face To Face ◽  
Estrogen Exposure ◽  
Age Related ◽  
Endogenous Estrogen ◽  
History Of ◽  
Ophthalmologic Examination ◽  
The University

The objective of this study is to evaluate the relationship between reproductive exposures and age-related cataract among women. This was a hospital based case-control study. The study population included female patients, aged 50 years and above who attended the Eye clinic at the University of Malaya Medical Centre. The outcome measurement was based on ophthalmologic examination by an ophthalmologist. The data on exposure was obtained from face to face interview using a structured questionnaire. In order to reduce the recall bias, patients' medical records were used to substantiate the exposure status. Multiple logistic regression was used to assess the association of age-related cataract with exogenous estrogen usage (HRT and OCP) and duration of menses. Important confounders such as age, history of diabetes, cigarette smoking and steroids usage were controlled for in the analysis. Females with 29 years or less of endogenous estrogen exposure of, have almost three times the risk of developing age related cataract (adjusted OR 3.42: 95% CI: 1.28,9.16), similarly among those with exposure of 30- 32 years (adjusted OR 3.64: 95% CI: 1.08,12.26). Hormone Replacement Therapy used for more than three years was found to be a protective factor of age-related cataract. There is evidence that reproductive exposure may play a role in reducing the occurrence of age-related cataract among Malaysian women. Asia Pac J Public Health 2007; 19(2): 23-28.

scholarly journals Association of central adiposity with psoriasis, psoriatic arthritis and rheumatoid arthritis: a cross-sectional study of the UK Biobank

Rheumatology ◽  
2019 ◽  
Vol 58 (12) ◽  
pp. 2137-2142 ◽  
Author(s):  
Lyn D Ferguson ◽  
Rosemary Brown ◽  
Carlos Celis-Morales ◽  
Paul Welsh ◽  
Donald M Lyall ◽  
...  
Keyword(s):  
Waist Circumference ◽  
Smoking Status ◽  
Cross Sectional Study ◽  
Central Adiposity ◽  
Uk Biobank ◽  
Sectional Study ◽  
Cross Sectional ◽  
Independent Association ◽  
The Uk

AbstractObjectivesTo determine the independent association of central adiposity, assessed by waist circumference, with odds of psoriasis, PsA and RA prevalence after controlling for general adiposity (BMI).MethodsA cross-sectional study of UK Biobank participants aged 40–70 years was performed. Logistic regression was used to calculate the odds of psoriasis, PsA and RA occurrence compared with controls without these conditions by waist circumference, adjusting for covariates: age, sex, smoking status, socioeconomic deprivation and self-reported physical activity (Model 1), followed additionally by BMI (Model 2).ResultsA total of 502 417 participants were included; 5074 with psoriasis (1.02%), 905 with PsA (0.18%), 5532 with RA (1.11%) and 490 906 controls without these conditions. Adjusted odds ratios (ORs) (Model 1) for psoriasis, PsA and RA, per s.d. (13.5 cm) higher waist circumference were 1.20 (95% CI 1.16, 1.23), 1.30 (95% CI 1.21, 1.39) and 1.21 (95% CI 1.17, 1.24), respectively (all P < 0.001). These ORs remained significant after further adjustment for BMI (Model 2) in psoriasis [OR 1.19 (95% CI 1.12, 1.27), P < 0.001] and RA [OR 1.19 (95% CI 1.12, 1.26), P < 0.001], but not in PsA [OR 1.11 (95% CI 0.95, 1.29), P = 0.127].ConclusionCentral adiposity as measured by waist circumference is associated with greater odds of psoriasis and RA prevalence after adjustment for confounders and for BMI. Our findings add support for central adiposity as a long-term clinically relevant component of these conditions.

scholarly journals Anthropometry, body fat composition and reproductive factors and risk of oesophageal and gastric cancer by subtype and subsite in the UK Biobank cohort

PLoS ONE ◽  
2020 ◽  
Vol 15 (10) ◽  
pp. e0240413
Author(s):  
Harinakshi Sanikini ◽  
David C. Muller ◽  
Marc Chadeau-Hyam ◽  
Neil Murphy ◽  
Marc J. Gunter ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Body Fat ◽  
Reproductive Factors ◽  
Uk Biobank ◽  
Fat Composition ◽  
The Uk

scholarly journals Walking pace improves all-cause and cardiovascular mortality risk prediction: A UK Biobank prognostic study

2019 ◽  
Vol 27 (10) ◽  
pp. 1036-1044 ◽  
Author(s):  
Stavroula Argyridou ◽  
Francesco Zaccardi ◽  
Melanie J Davies ◽  
Kamlesh Khunti ◽  
Thomas Yates
Keyword(s):  
Risk Factors ◽  
Risk Prediction ◽  
Cardiovascular Mortality ◽  
Smoking Status ◽  
Density Lipoprotein ◽  
Uk Biobank ◽  
All Cause Mortality ◽  
Lifestyle Measures ◽  
European Society Of Cardiology ◽  
The Uk

Aims The purpose of this study was to quantify and rank the prognostic relevance of dietary, physical activity and physical function factors in predicting all-cause and cardiovascular mortality in comparison with the established risk factors included in the European Society of Cardiology Systematic COronary Risk Evaluation (SCORE). Methods We examined the predictive discrimination of lifestyle measures using C-index and R2 in sex-stratified analyses adjusted for: model 1, age; model 2, SCORE variables (age, smoking status, systolic blood pressure, total and high-density lipoprotein cholesterol). Results The sample comprised 298,829 adults (median age, 57 years; 53.5% women) from the UK Biobank free from cancer and cardiovascular disease at baseline. Over a median follow-up of 6.9 years, there were 2174 and 3522 all–cause and 286 and 796 cardiovascular deaths in women and men, respectively. When added to model 1, self-reported walking pace improved C-index in women and men by 0.013 (99% CI: 0.007–0.020) and 0.022 (0.017–0.028) respectively for all-cause mortality; and by 0.023 (0.005–0.042) and 0.034 (0.020–0.048) respectively for cardiovascular mortality. When added to model 2, corresponding values for women and men were: 0.008 (0.003–0.012) and 0.013 (0.009–0.017) for all-cause mortality; and 0.012 (–0.001–0.025) and 0.024 (0.013–0.035) for cardiovascular mortality. Other lifestyle factors did not consistently improve discrimination across models and outcomes. The pattern of results for R2 mirrored those for C-index. Conclusion A simple self-reported measure of walking pace was the only lifestyle variable found to improve risk prediction for all-cause and cardiovascular mortality when added to established risk factors.

EXPRESS: Porphyria Cutanea Tarda precipitated by ovarian stimulation during oocyte retrieval in a genetically susceptible female

2021 ◽  
pp. 000456322098803
Author(s):  
Erum Rasheed ◽  
Sarah Savage ◽  
Elena Walsh ◽  
Nadia Brazil ◽  
Nicola Ralph ◽  
...  
Keyword(s):  
Oral Contraceptive ◽  
Ovarian Stimulation ◽  
Porphyria Cutanea Tarda ◽  
Hormone Replacement ◽  
Oocyte Retrieval ◽  
Fertility Treatment ◽  
Single Cycle ◽  
Oral Contraceptive Pills ◽  
Oral Estrogen ◽  
Contraceptive Pills

We report a case of 33-year old female with underlying genetic susceptibility for familial porphyria cutanea tarda (PCT) due to novel UROD variant (c.636+2 dupT) unmasked by transient exposure to supraphysiological estrogen levels following a single cycle of successful controlled ovarian stimulation for oocyte retrieval. Use of oral estrogen in the form of oral contraceptive pills and hormone replacement therapy has been well known to trigger active PCT phenotype in susceptible women. However, to date the emergence of clinically overt PCT has not been reported in association with fertility treatment in the literature before. Keywords: Familial PCT, UROD mutation, Ovarian stimulation, Estrogen

scholarly journals Population-specific Interaction of the TRIM46 / MUC1 Locus With Cigarette Smoking May Influence the Risk of Gout

2020 ◽  
Author(s):  
Niamh Catherine Fanning ◽  
Ruth K Topless ◽  
Amanda Phipps-Green ◽  
John F Pearson ◽  
Murray Cadzow ◽  
...  
Keyword(s):  
South Asian ◽  
Smoking Status ◽  
Current Smoker ◽  
Uk Biobank ◽  
Additive Interaction ◽  
Increased Risk ◽  
East And West ◽  
The Uk ◽  
Sample Set ◽  
Asian Sample

Abstract Background: Epidemiological and prospective studies suggest that current-smoking may be protective against developing gout and that smoking cessation may increase risk. The aim of this study was to identify interactions between smoking, genetic risk variants and the risk of gout. Methods: A cohort of 520 New Zealand (NZ) East and West Polynesian participants with and 629 without gout were included in our discovery analysis. A cohort of European participants (7576 with and 364,445 without) and South Asian participants (156 with and 7504 without gout) of the UK Biobank were used for replication. Five loci with previous evidence of smoking-influenced associations with serum urate levels were tested for their interaction with smoking status (current-smoker or ex-smoker vs. never-smoker as the reference group) in determining gout risk. The 5 loci were in genes, SLC2A9, ABCG2, GCKR, TRIM46, and HNF4G.Results: A non-additive interaction between genotype and smoking on gout risk was observed between ex-smoker status and TRIM46 (rs11264341) in NZ East and West Polynesian people [interaction ORmeta = 0.58 (0.37-0.92), p = 0.021], but not in European (OR = 0.94 (0.88-1.01), p = 0.10) or South Asian (0.96 (0.55-1.66), p = 0.88) participants of the UK Biobank. TRIM46 (rs11264341) interacted with current-smoker status in the Asian UK Biobank cohort [interaction OR = 2.68 (1.26-5.68), p = 0.010]. In smoking status subgroups the C-allele of rs11264341 increased risk of gout specifically in never-smokers (OR= 1.41 (1.04-1.92), p = 0.029) of the NZ Polynesian sample set and in current-smokers (2.39 (1.13-5.05), p=0.022) of the South Asian sample set. There was no evidence of interaction between smoking-status and the 4 remaining loci in 2 or more of the ancestral populations analysed in this study.Conclusion: We provide evidence for a non-additive interaction between TRIM46 (rs11264341) and smoking behaviour associated with gout risk in a NZ Polynesian sample set and a South Asian sample set, but not in a European sample set. MUC1, that encodes a transmembrane mucin in the lungs whose expression and function is affected by cigarette smoke, is a possible candidate gene at the TRIM46 locus.

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