Protective role of serum albumin in dementia: a prospective study from United Kingdom biobank.

Background: A number of studies have explored the link between neurodegenerative disorders (NDDs) and albumin, the main protein in human plasma. However, the results have been inconsistent, highlighting the necessity for a detailed systemic analysis. Methods: Utilizing data from the United Kingdom Biobank, we investigated the relationship between baseline levels of serum and urine albumin and the occurrence of common NDDs, including Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and dementia, employing Cox proportional hazards regression analysis. Results: Our results reveal that elevated baseline serum albumin levels are linked to a decreased risk of developing dementia (beta = -0.024, SE = 0.004, p < 0.001). Subgroup and interaction analyses highlighted the impact of factors like body mass index (BMI), age, and alcohol consumption on this relationship. Specifically, participants with higher BMI, younger age, or lower alcohol intake exhibited a stronger protective effect. On the other hand, a higher baseline level of urine microalbumin was connected to a slight increase in dementia risk (beta = 0.003, SE = 3.30E-04, p < 0.001). No significant associations were found between albumin levels and the risk of PD or ALS. Conclusion: Our study underscores the potential role of serum albumin as a biomarker associated with reduced dementia risk. These findings contribute valuable insights into the understanding of albumin's impact on NDDs, suggesting its utility as a biomarker for dementia in clinical settings and informing future therapeutic strategies in clinical trials.

Association Between Natural Hair Color, Race, and Alopecia.

INTRODUCTION: Limited epidemiologic data has suggested direct associations between hair pigment, race, and incidence of alopecia areata (AA). Here, we examine the relationship between natural hair color, race, and the lifetime risk alopecia. METHODS: In this case-control study, we included UK Biobank patients of all races and self-reported hair color with diagnoses of AA, androgenetic alopecia (AGA), or scarring alopecia (SA). Multivariable logistic regression was used to detect differences in lifetime risk. RESULTS: Findings reveal a significantly increased risk of AA among individuals with black hair compared to dark brown hair (OR 1.71 [95% CI 1.22-2.38], p < 0.001). Those with red or blonde hair showed a decreased risk of AA (0.74 [0.56-0.97]; 0.62 [0.41-0.95], p < 0.05). No racial differences in AA prevalence were observed among individuals with black hair. CONCLUSIONS: Darker hair colors may be associated with a higher risk of AA, lighter hair colors with a lower risk, and differences in hair color could contribute to previously noted racial variations in AA incidence, potentially influencing dermatologists' perspectives on the disease's epidemiology.

Trans-ancestry polygenic models for the prediction of LDL blood levels: an analysis of the United Kingdom Biobank and Taiwan Biobank.

Polygenic risk score (PRS) predictions often show bias toward the population of available genome-wide association studies (GWASs), which is typically of European ancestry. This study aimed to assess the performance differences of ancestry-specific PRS and test the implementation of multi-ancestry PRS to enhance the generalizability of low-density lipoprotein (LDL) cholesterol predictions in the East Asian (EAS) population. In this study, we computed ancestry-specific and multi-ancestry PRSs for LDL using data obtained from the Global Lipid Genetics Consortium, while accounting for population-specific linkage disequilibrium patterns using the PRS-CSx method in the United Kingdom Biobank dataset (UKB, n = 423,596) and Taiwan Biobank dataset (TWB, n = 68,978). Population-specific PRSs were able to predict LDL levels better within the target population, whereas multi-ancestry PRSs were more generalizable. In the TWB dataset, covariate-adjusted R 2 values were 9.3% for ancestry-specific PRS, 6.7% for multi-ancestry PRS, and 4.5% for European-specific PRS. Similar trends (8.6%, 7.8%, and 6.2%) were observed in the smaller EAS population of the UKB (n = 1,480). Consistent with R 2 values, PRS stratification in EAS regions (TWB) effectively captured a heterogenous variability in LDL blood cholesterol levels across PRS strata. The mean difference in LDL levels between the lowest and highest EAS-specific PRS (EAS_PRS) deciles was 0.82, compared to 0.59 for European-specific PRS (EUR_PRS) and 0.76 for multi-ancestry PRS. Notably, the mean LDL values in the top decile of multi-ancestry PRS were comparable to those of EAS_PRS (3.543 vs. 3.541, p = 0.86). Our analysis of the PRS prediction model for LDL cholesterol further supports the issue of PRS generalizability across populations. Our targeted analysis of the EAS population revealed that integrating non-European genotyping data with a powerful European-based GWAS can enhance the generalizability of LDL PRS.

C-Reactive protein and cognition: Mediation analyses with brain morphology in the UK Biobank.

Cognitive impairments and abnormal immune activity are both associated with various clinical disorders. The association between C-Reactive protein (CRP), a marker associated with inflammation, and cognitive performance remains unclear. Further, mechanisms potentially linking CRP to cognition are not yet established. Brain structure may well mediate this relationship: immune processes play crucial roles in shaping and maintaining brain structure, with brain structure and function driving cognition. The United Kingdom Biobank (UKBB) is a large cohort study with extensive assessments, including high-sensitivity serum CRP levels, brain imaging, and various cognitive tasks. With data from 39,200 UKBB participants, we aimed first to determine the relationship between CRP and cognitive performance, and second, to assess metrics of brain morphology as potential mediators in this relationship. Participants were aged 40 to 70 at initial assessment and were mostly Caucasian. After accounting for potential covariates (e.g., age, sex, medical diagnoses, use of selective-serotonin reuptake inhibitors), we found CRP levels to have small, negative associations with fluid intelligence (b = -0.03, 95%CI[-0.05,-0.02], t(14381) = -3.62, pcor = .004), and numeric memory (b = -0.03, 95%CI[-0.05,-0.01], t(14366) = -3.31, pcor = .007). We found no evidence of brain morphology mediating these relationships (all |ab| < 0.001, all pcor > .55). Our findings from this large sample suggest that serum-assessed CRP is of marginal importance for cognitive performance in mid-to-late aged Caucasians; the small effect sizes of statistically significant associations provide context to previous inconsistent results. The seeming lack of involvement of brain morphology suggests that other brain metrics (e.g., connectivity, functional activation) may be more pertinent to this relationship. Future work should also consider CRP levels measured in the central nervous system and/or other cytokines that may better predict cognitive performance in this population.

Variants in JAZF1 are associated with asthma, type 2 diabetes, and height in the United Kingdom biobank population.

Background: Asthma, type 2 diabetes (T2D), and anthropometric measures are correlated complex traits that all have a major genetic component. Objective: To investigate the overlap in genetic variants associated with these complex traits. Methods: Using United Kingdom Biobank data, we performed univariate association analysis, fine-mapping, and mediation analysis to identify and dissect shared genomic regions associated with asthma, T2D, height, weight, body mass index (BMI), and waist circumference (WC). Results: We found several genome-wide significant variants in and around the JAZF1 gene that are associated with asthma, T2D, or height with two of these variants shared by the three phenotypes. We also observed an association in this region with WC when adjusted for BMI. However, there was no association with WC when it was not adjusted for BMI or weight. Additionally, only suggestive associations between variants in this region and BMI were observed. Fine-mapping analyses suggested that within JAZF1 there are non-overlapping regions harboring causal susceptibility variants for asthma, T2D, and height. Mediation analyses supported the conclusion that these are independent associations. Conclusion: Our findings indicate that variants in the JAZF1 are associated with asthma, T2D, and height, but the associated causal variant(s) are different for each of the three phenotypes.

Effect of proton pump inhibitors on the risk of chronic kidney disease: A propensity score-based overlap weight analysis using the United Kingdom Biobank.

Background: Proton pump inhibitors (PPIs) are widely used and have been linked to kidney diseases. However, the role of PPI use in the development of chronic kidney disease (CKD) remains unclear. We undertook this study to examine the association between PPI use and the subsequent risk of CKD. Methods: This is a prospective analysis of 462,421 participants free of cancer diagnosis or chronic kidney disease from the United Kingdom Biobank. Self-reported PPI use was recorded using an electronic questionnaire and confirmed by a trained staff. Incident CKD was identified based on the medical history. Overlap propensity score weighting with the Cox model was used to calculate the effect of PPI use on CKD risk. The number needed to harm (NNH) was calculated at 5 and 10 years of follow-up. Results: We documented 7,031 cases of CKD over a median follow-up of 8.1 years. Overlap propensity score weighting analysis showed that regular PPI users had a 37% higher risk of CKD incident than non-users (HR 1.37, 95% CI 1.28-1.47). The association persisted across subgroup analyses, different types of PPIs, and several sensitivity analyses. Quantitative bias analysis indicated that the result was robust to unmeasured confounding (E-value 2.08, lower 95% CI 1.88). The NNH was 147.9 and 78.6 for 5 and 10 years of follow-up, respectively. A head-to-head comparison showed that PPI users had a 19% higher risk of CKD than H2RA users (HR 1.19, 95% CI 1.02-1.39). Conclusion: The regular use of PPI is associated with a higher risk of CKD. Healthcare providers should carefully weigh up the potential benefits against the risk in prescribing PPIs, particularly for patients requiring long-term treatment.

The Risk of Hearing Impairment From Ambient Air Pollution and the Moderating Effect of a Healthy Diet: Findings From the United Kingdom Biobank.

The link between hearing impairment and air pollution has not been established, and the moderating effect of a healthy diet has never been investigated before. The purpose of this study was to investigate the association between air pollution and hearing impairment in British adults aged 37-73 years, and whether the association was modified by a healthy diet. We performed a cross-sectional population-based study with 158,811 participants who provided data from United Kingdom Biobank. A multivariate logistic regression model was used to investigate the link between air pollution and hearing impairment. Subgroup and effect modification analyses were carried out according to healthy diet scores, gender, and age. In the fully adjusted model, we found that exposure to PM10, NOX, and NO2 was associated with hearing impairment [PM10: odds ratio (OR) = 1.15, 95% confidence interval (95% CI) 1.02-1.30, P = 0.023; NOX: OR = 1.02, 95% CI 1.00-1.03, P = 0.040; NO2: OR = 1.03, 95% CI 1.01-1.06, P = 0.044], while PM2.5 and PM2.5 absorbance did not show similar associations. We discovered an interactive effect of age and air pollution on hearing impairment, but a healthy diet did not. The findings suggested that exposure to PM10, NOX and NO2 was linked to hearing impairment in British adults, whereas PM2.5 and PM2.5 absorbance did not show similar associations. These may help researchers focus more on the impact of air pollution on hearing impairment and provide a basis for developing effective prevention strategies.

Gender-specific association between the regular use of statins and the risk of irritable bowel syndrome: A population-based prospective cohort study.

Introduction: In addition to lipid-lowering effects, statins might modulate the gut microbiome and alleviate systematic inflammation, which in turn, may have a protective effect against irritable bowel syndrome (IBS). The aim of our study was to evaluate the gender-specific association between statin exposure and the risk of IBS. Method: We undertook a prospective analysis based on the United Kingdom Biobank, a large ongoing cohort including 477,293 participants aged 37-73 years. We included participants based on information on their personal statin use and also those free of IBS and cancer at the baseline. We evaluated the gender-specific hazard ratio (HR) and 95% confidence interval (CI) with Cox proportional hazards regression, adjusting for demographic factors, lifestyle factors, comorbidities, and statin indications. Result: A total of 438,805 participants (206,499 males and 232,306 females) were included in the analysis. Among male participants, the regular use of statins was associated with a decreased risk of IBS (HR: 0.77; 95% CI: 0.61-0.97). This association persists across multiple sensitivity and subgroup analyses and did not show clear evidence of variance among the major types of statins. We did not find sufficient evidence of the association between the statin use and IBS risk in females (HR: 0.98; 95% CI: 0.82-1.16). Conclusion: Our study found that the regular use of statins was associated with a decreased risk of IBS in male participants. Further studies are required to confirm the beneficial effect of statins.

Pathway Association Studies Reveal Gene Loci and Pathway Networks that Associated With Plasma Cystatin C Levels.

As a marker for glomerular filtration, plasma cystatin C level is used to evaluate kidney function. To decipher genetic factors that control the plasma cystatin C level, we performed genome-wide association and pathway association studies using United Kingdom Biobank data. One hundred fifteen loci yielded p values less than 1 × 10-100, three genes (clusters) showed the most significant associations, including the CST8-CST9 cluster on chromosome 20, the SH2B3-ATXN2 gene region on chromosome 12, and the SHROOM3-CCDC158 gene region on chromosome 4. In pathway association studies, forty significant pathways had FDR (false discovery rate) and or FWER (family-wise error rate) ≤ 0.001: spermatogenesis, leukocyte trans-endothelial migration, cell adhesion, glycoprotein, membrane lipid, steroid metabolic process, and insulin signaling pathways were among the most significant pathways that associated with the plasma cystatin C levels. We also performed Genome-wide association studies for eGFR, top associated genes were largely overlapped with those for cystatin C.