A causal relationship between particulate matter 2.5 and obesity and its related indicators: a Mendelian randomization study of European ancestry.

Background: In recent years, the prevalence of obesity has continued to increase as a global health concern. Numerous epidemiological studies have confirmed the long-term effects of exposure to ambient air pollutant particulate matter 2.5 (PM2.5) on obesity, but their relationship remains ambiguous. Methods: Utilizing large-scale publicly available genome-wide association studies (GWAS), we conducted univariate and multivariate Mendelian randomization (MR) analyses to assess the causal effect of PM2.5 exposure on obesity and its related indicators. The primary outcome given for both univariate MR (UVMR) and multivariate MR (MVMR) is the estimation utilizing the inverse variance weighted (IVW) method. The weighted median, MR-Egger, and maximum likelihood techniques were employed for UVMR, while the MVMR-Lasso method was applied for MVMR in the supplementary analyses. In addition, we conducted a series of thorough sensitivity studies to determine the accuracy of our MR findings. Results: The UVMR analysis demonstrated a significant association between PM2.5 exposure and an increased risk of obesity, as indicated by the IVW model (odds ratio [OR]: 6.427; 95% confidence interval [CI]: 1.881-21.968; P FDR = 0.005). Additionally, PM2.5 concentrations were positively associated with fat distribution metrics, including visceral adipose tissue (VAT) (OR: 1.861; 95% CI: 1.244-2.776; P FDR = 0.004), particularly pancreatic fat (OR: 3.499; 95% CI: 2.092-5.855; PFDR =1.28E-05), and abdominal subcutaneous adipose tissue (ASAT) volume (OR: 1.773; 95% CI: 1.106-2.841; P FDR = 0.019). Furthermore, PM2.5 exposure correlated positively with markers of glucose and lipid metabolism, specifically triglycerides (TG) (OR: 19.959; 95% CI: 1.269-3.022; P FDR = 0.004) and glycated hemoglobin (HbA1c) (OR: 2.462; 95% CI: 1.34-4.649; P FDR = 0.007). Finally, a significant negative association was observed between PM2.5 concentrations and levels of the novel obesity-related biomarker fibroblast growth factor 21 (FGF-21) (OR: 0.148; 95% CI: 0.025-0.89; P FDR = 0.037). After adjusting for confounding factors, including external smoke exposure, physical activity, educational attainment (EA), participation in sports clubs or gym leisure activities, and Townsend deprivation index at recruitment (TDI), the MVMR analysis revealed that PM2.5 levels maintained significant associations with pancreatic fat, HbA1c, and FGF-21. Conclusion: Our MR study demonstrates conclusively that higher PM2.5 concentrations are associated with an increased risk of obesity-related indicators such as pancreatic fat content, HbA1c, and FGF-21. The potential mechanisms require additional investigation.

Baseline levels and longitudinal changes in plasma Aß42/40 among Black and white individuals.

Blood-based biomarkers of Alzheimer disease (AD) may facilitate testing of historically under-represented groups. The Study of Race to Understand Alzheimer Biomarkers (SORTOUT-AB) is a multi-center longitudinal study to compare AD biomarkers in participants who identify their race as either Black or white. Plasma samples from 324 Black and 1,547 white participants underwent analysis with C2N Diagnostics' PrecivityAD test for Aß42 and Aß40. Compared to white individuals, Black individuals had higher average plasma Aß42/40 levels at baseline, consistent with a lower average level of amyloid pathology. Interestingly, this difference resulted from lower average levels of plasma Aß40 in Black participants. Despite the differences, Black and white individuals had similar longitudinal rates of change in Aß42/40, consistent with a similar rate of amyloid accumulation. Our results agree with multiple recent studies demonstrating a lower prevalence of amyloid pathology in Black individuals, and additionally suggest that amyloid accumulates consistently across both groups.

Racial disparities in colorectal cancer outcomes and access to care: a multi-cohort analysis.

Introduction: Non-Hispanic Black (NHB) Americans have a higher incidence of colorectal cancer (CRC) and worse survival than non-Hispanic white (NHW) Americans, but the relative contributions of biological versus access to care remain poorly characterized. This study used two nationwide cohorts in different healthcare contexts to study health system effects on this disparity. Methods: We used data from the Surveillance, Epidemiology, and End Results (SEER) registry as well as the United States Veterans Health Administration (VA) to identify adults diagnosed with colorectal cancer between 2010 and 2020 who identified as non-Hispanic Black (NHB) or non-Hispanic white (NHW). Stratified survival analyses were performed using a primary endpoint of overall survival, and sensitivity analyses were performed using cancer-specific survival. Results: We identified 263,893 CRC patients in the SEER registry (36,662 (14%) NHB; 226,271 (86%) NHW) and 24,375 VA patients (4,860 (20%) NHB; 19,515 (80%) NHW). In the SEER registry, NHB patients had worse OS than NHW patients: median OS of 57 months (95% confidence interval (CI) 55-58) versus 72 months (95% CI 71-73) (hazard ratio (HR) 1.14, 95% CI 1.12-1.15, p = 0.001). In contrast, VA NHB median OS was 65 months (95% CI 62-69) versus NHW 69 months (95% CI 97-71) (HR 1.02, 95% CI 0.98-1.07, p = 0.375). There was significant interaction in the SEER registry between race and Medicare age eligibility (p < 0.001); NHB race had more effect in patients <65 years old (HR 1.44, 95% CI 1.39-1.49, p < 0.001) than in those ≥65 (HR 1.13, 95% CI 1.11-1.15, p < 0.001). In the VA, age stratification was not significant (p = 0.21). Discussion: Racial disparities in CRC survival in the general US population are significantly attenuated in Medicare-aged patients. This pattern is not present in the VA, suggesting that access to care may be an important component of racial disparities in this disease.

Emergent inequity of glycaemic metrics for Maori children with type 1 diabetes is negated by early use of continuous glucose monitoring.

AIM: We investigated if continuous glucose monitoring (CGM) in children with type 1 diabetes (T1D) within 12 months of being diagnosed modifies the development of glycaemic outcome inequity on the basis of either ethnicity or socio-economic status (SES). METHOD: De-identified clinical and SES data from the KIWIDIAB data network were collected 12 months after diagnosis in children under 15 years diagnosed with T1D between 1 October 2020 and 1 October 2021. RESULTS: There were 206 children with new onset T1D: CGM use was 56.7% for Maori and 77.2% for Europeans. Mean (SD) HbA1c was 62.4 (14.2) mmol/mol at 12 months post diagnosis, but Maori were 9.4mmol/mol higher compared to Europeans (p<0.001). For those without CGM, Maori had an HbA1c 10.8 (95% CI 2.3 to 19.4, p=0.013) mmol/mol higher than Europeans, whereas there was no evidence of a difference between Maori and Europeans using CGM (62.1 [9.3] mmol/mol vs 58.5 [12.4] mmol/mol p=0.53 respectively). Comparing quintiles of SES, HbA1c was 10.8 (95% CI 4.7 to 16.9, p<0.001) mmol/mol higher in the lowest quintile of SES compared to the highest. CONCLUSION: These observational data suggest CGM use ameliorates the ethnic disparity in HbA1c at 12 months in new onset T1D.

Exploring the causal association between uric acid and lung cancer in east Asian and European populations: a mendelian randomization study.

BACKGROUND: Lung cancer still ranks first in the mortality rate of cancer. Uric acid is a product of purine metabolism in humans. Its presence in the serum is controversial; some say that its high levels have a protective effect against tumors, others say the opposite, that is, high levels increase the risk of cancer. Therefore, the aim of this study was to investigate the potential causal association between serum uric acid levels and lung cancer. METHODS: Mendelian randomization was used to achieve our aim. Sensitivity analyses was performed to validate the reliability of the results, followed by reverse Mendelian analyses to determine a potential reverse causal association. RESULTS: A significant causal association was found between serum uric acid levels and lung cancer in East Asian and European populations. Further sublayer analysis revealed a significant causal association between uric acid and small cell lung cancer, while no potential association was observed between uric acid and non-small cell lung cancer, squamous lung cancer, and lung adenocarcinoma. The sensitivity analyses confirmed the reliability of the results. Reverse Mendelian analysis showed no reverse causal association between uric acid and lung cancer. CONCLUSIONS: The results of this study suggested that serum uric acid levels were negatively associated with lung cancer, with uric acid being a potential protective factor for lung cancer. In addition, uric acid level monitoring was simple and inexpensive. Therefore, it might be used as a biomarker for lung cancer, promoting its wide use clinical practice.

The impact of air pollution on the facial skin of Caucasian women using real-life pollutant exposure measurements.

BACKGROUND: To date, studies examining the effect of air pollution on skin characteristics have relied on regional pollution estimates obtained from fixed monitoring sites. Hence, there remains a need to characterize the impact of air pollution in vivo in real-time conditions. We conducted an initial investigation under real-life conditions, with the purpose of characterizing the in vivo impact of various pollutants on the facial skin condition of women living in Paris over a 6-month period. MATERIALS AND METHODS: A smartphone application linked to the Breezometer platform was used to collect participants' individual exposures to pollutants through the recovery of global positioning system (GPS) data over a 6-month period. Daily exposure to fine particulate matter (PM 2.5 µm and PM 10 µm), pollen, and air quality was measured. Facial skin color, roughness, pore, hydration, elasticity, and wrinkle measurements were taken at the end of the 6-month period. Participants' cumulated pollutant exposure over 6 months was calculated. Data were stratified into two groups (lower vs. higher pollutant exposure) for each pollutant. RESULTS: 156 women (20-60 years-old) were recruited, with 124 women completing the study. Higher PM 2.5 µm exposure was associated with altered skin color and increased roughness under the eye. Higher PM 10 µm exposure with increased wrinkles and roughness under the eye, increased pore appearance, and decreased skin hydration. Exposure to poorer air quality was linked with increased forehead wrinkles and decreased skin elasticity, while higher pollen exposure increased skin roughness and crow's feet. CONCLUSION: This study suggests a potential correlation between air pollution and facial skin in real-life conditions. Prolonged exposure to PM, gases, and pollen may be linked to clinical signs of skin ageing. This study highlights the importance of longer monitoring over time in real conditions to characterize the effect of pollution on the skin.

Betaine and I-LG may have a predictive value for ATB: A causal study in a large European population.

PURPOSE: To analyze the causal relationship between 486 human serum metabolites and the active tuberculosis (ATB) in European population. METHODS: In this study, the causal relationship between human serum metabolites and the ATB was analyzed by integrating the genome-wide association study (GWAS). The 486 human serum metabolites were used as the exposure variable, three different ATB GWAS databases in the European population were set as outcome variables, and single nucleotide polymorphisms were used as instrumental variables for Mendelian Randomization. The inverse variance weighting was estimated causality, the MR-Egger intercept to estimate horizontal pleiotropy, and the combined effects of metabolites were also considered in the meta-analysis. Furthermore, the web-based MetaboAnalyst 6.0 was engaged for enrichment pathway analysis, while R (version 4.3.2) software and Review Manager 5.3 were employed for statistical analysis. RESULTS: A total of 21, 17, and 19 metabolites strongly associated with ATB were found in the three databases after preliminary screening (P < 0.05). The intersecting metabolites across these databases included tryptophan, betaine, 1-linoleoylglycerol (1-monolinolein) (1-LG), 1-eicosatrienoylglycerophosphocholine, and oleoylcarnitine. Among them, betaine (I2 = 24%, P = 0.27) and 1-LG (I2 = 0%, P = 0.62) showed the lowest heterogeneity among the different ATB databases. In addition, the metabolic pathways of phosphatidylethanolamine biosynthesis (P = 0.0068), methionine metabolism (P = 0.0089), betaine metabolism (P = 0.0205) and oxidation of branched-chain fatty acids (P = 0.0309) were also associated with ATB. CONCLUSION: Betaine and 1-LG may be biomarkers or auxiliary diagnostic tools for ATB. They may provide new guidance for medical practice in the early diagnosis and surveillance of ATB. In addition, by interfering with phosphatidylethanolamine biosynthesis, methionine metabolism, betaine metabolism, oxidation of branched-chain fatty acids, and other pathways, it is helpful to develop new anti-tuberculosis drugs and explore the virulence or pathogenesis of ATB at a deeper level, providing an effective reference for future studies.

Comparison Between Black Non-Hispanic and White Non-Hispanic Simultaneous Pancreas-Kidney Transplant Candidates and Recipients.

INTRODUCTION: This study examined simultaneous pancreas-kidney transplant (SPKt) in Black and White patients to identify disparities in transplantation, days on the waitlist, and reasons for SPKt waitlist removal. METHODS: Using the United Network for Organ Sharing Standard Transplant Analysis and Research file, patients between January 1, 2009, and May 31, 2021, were included. Three cohorts (overall, SPKt recipients only, and those not transplanted) were selected using propensity score matching. Conditional logistic regression was used for categorical outcomes. Days on the waitlist were compared using negative binomial regression. RESULTS: Black patients had increased odds of receiving a  SPKt (OR, 1.25 [95% CI, 1.11-1.40], p < 0.001). White patients had increased odds of receiving a kidney-only transplant (OR 0.48 [95% CI, 0.38-0.61], p < 0.001), and specifically increased odds of receiving a living donor kidney (OR 0.34 [0.25-0.45], p < 0.001). CONCLUSION: This study found that Black patients are more likely to receive a SPKt. Results suggest that there are opportunities for additional inquiry related to patient removal from the waitlist, particularly considering White patients received or accepted more kidney-only transplants and were more likely to receive a living donor kidney-only transplant.

Correction to "Defining racial allies: A qualitative investigation of White allyship from the perspective of people of color" by Hinger et al. (2023).

Reports an error in "Defining racial allies: A qualitative investigation of White allyship from the perspective of people of color" by Cassandra L. Hinger, Cirleen DeBlaere, Rebecca Gwira, Michelle Aiello, Arash Punjwani, Laura Cobourne, Ngoc Tran, Madison Lord, Jordan Mike and Carlton Green (Journal of Counseling Psychology, 2023[Nov], Vol 70[6], 631-644). An additional citation was added for the structure of the definition of White allies in the second paragraph of the introduction. The online version of this article has been corrected. (The following abstract of the original article appeared in record 2024-23216-002.) While interdisciplinary scholars and activists urge White allies to engage in racial justice work led by the voices of Black, Indigenous, and people of color (BIPOC), to date, most research on racial allyship has centered exclusively on the perspective of White allies themselves. Thus, the purpose of this study was to create a framework of racial allyship from the perspective of BIPOC. Utilizing constructivist grounded theory (Charmaz, 2014), focus groups were conducted to understand how BIPOC describe the knowledge, skills, and actions of White allies. Participants across eight focus groups described allyship as an ongoing interpersonal process that included a lifelong commitment to (a) building trust, (b) engaging in antiracist action, (c) critical awareness, (d) sociopolitical knowledge, (e) accountability, and (f) communicating and disseminating information. The findings of this study point to several avenues through which White counseling psychologists can incorporate racial allyship in their research, training, clinical, and advocacy work that align with our field's emphasis on social justice, multiculturalism, and prevention. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Disparate Rates of Germline Variants in Cancer Predisposition Genes in African American/Black Compared With Non-Hispanic White Individuals Between 2015 and 2022.

PURPOSE: African American/Black (AA/B) individuals are under-represented in genomic databases and thus less likely to receive definitive information from germline genetic testing (GGT) than non-Hispanic White (NHW) individuals. With nearly 500,000 AA/B and NHW individuals having undergone multigene panel testing (MGPT) for hereditary cancer risk at a single commercial laboratory, to our knowledge, we present the largest study to date investigating cancer GGT results in AA/B and NHW individuals. METHODS: MGPT results from a retrospective cohort of AA/B (n = 48,684) and NHW (n = 444,831) patients were evaluated. Frequencies of pathogenic germline variants (PGVs) and variants of uncertain significance (VUS) were compared between AA/B and NHW individuals. Changes in frequency of VUS over time were determined. Pearson's chi-squared test was used to compare categorical variables among groups. All significance tests were two-tailed, and P < .05 was considered statistically significant. RESULTS: Between 2015 and 2022, rates of VUS decreased 2.3-fold in AA/B and 1.8-fold in NHW individuals; however, frequencies of VUS and PGV remained significantly higher (46% v 32%; P < .0001) and lower (9% v 13%; P < .0001) in AA/B compared with NHW individuals. Rates of VUS in ATM, BRCA1, BRCA2, PALB2, and PMS2 were significantly higher in AA/B compared with NHW individuals, whereas rates of PGV in BRCA1, BRCA2, and PALB2 were higher in AA/B compared with NHW individuals (P < .001). CONCLUSION: Despite reductions in VUS frequencies over time, disparities in definitive GGT results persist. Increasing inclusion of AA/B populations in both testing and research will further increase knowledge of genetic variants across these racial groups.

Implicit bias and experience influence overall but not relative trustworthiness judgment of other-race faces.

Impressions of trustworthiness are formed quickly from faces. To what extent are these impressions shared among observers of the same or different races? Although high consensus of trustworthiness evaluation has been consistently reported, recent studies suggested substantial individual differences. For instance, negative implicit racial bias and low contact experience towards individuals of the other race have been shown to be related to low trustworthiness judgments for other-race faces. This pre-registered study further examined the effects of implicit social bias and experience on trustworthiness judgments of other-race faces. A relatively large sample of White (N = 338) and Black (N = 299) participants completed three tasks: a trustworthiness rating task of faces, a race implicit association test, and a questionnaire of experience. Each participant rated trustworthiness of 100 White faces and 100 Black faces. We found that the overall trustworthiness ratings for other-race faces were influenced by both implicit bias and experience with individuals of the other-race. Nonetheless, when comparing to the own-race baseline ratings, high correlations were observed for the relative differences in trustworthiness ratings of other-race faces for participants with varied levels of implicit bias and experience. These results suggest differential impact of social concepts (e.g., implicit bias, experience) vs. instinct (e.g., decision of approach-vs-avoid) on trustworthiness impressions, as revealed by overall vs. relative ratings on other-race faces.

Prevalence of trochlear dysplasia in an 1162 retrospective cohort study using CT scans.

HYPOTHESIS/PURPOSE: The prevalence of trochlear dysplasia is common in different populations. BACKGROUND: The prevalence of trochlear dysplasia in the general population, categorised by sex, race, age, and body mass index, has been sparse. This study aimed to define the prevalence of trochlear dysplasia based on the latter categories. STUDY DESIGN: Cohort retrospective study. METHODS: 1162 skeletal mature healthy femora were obtained from a CT-scan-based modelling system (SOMA). Thin slice CT scans were acquired exclusively for medical indications such as polytrauma (20%), CT angiography (70%) and other reasons (i.e. Total Joint Replacement) (10%). Trochlear dysplasia was measured using Pfirmann's method. Patient demographics such as age, race and sex were recorded. RESULTS: The overall prevalence of trochlear dysplasia is 4.5% and is far more common in Asian female patients compared to Caucasian, African and Middle Eastern knees. CONCLUSION: Overall, the prevalence of dysplasia in the general population was determined to be 4.5%, with female patients being more likely to suffer from the condition. Patients of Asian and Caucasian race were more likely to have trochlear dysplasia, while Middle Eastern male patients displayed more dysplastic values than their female counterparts.

Caucasian validation of downstaging from IIB to IIA in T1N1M0 patients within the 9th edition of the non-small cell lung cancer tumor-node-metastasis staging.

BACKGROUND: The 9th edition of the lung cancer tumor-node-metastasis (TNM) staging introduced adjustments, including the reclassification of T1N1M0 patients from stage IIB to IIA. This update used data mostly from Asian populations. However, the applicability of these adjustments to Caucasian patients remains uncertain. METHODS: Stage II non-small cell lung cancer (NSCLC) patients from the Surveillance, Epidemiology, and End Results (SEER) database were included. Kaplan-Meier analysis with log-rank testing compared overall survival (OS) and cancer-specific survival (CSS). Propensity score matching (PSM) balanced baseline characteristics. The least absolute shrinkage and selection operator (LASSO)-based Cox analyses identified prognostic factors. RESULTS: Among 10,470 eligible stage II NSCLC patients (median age: 69 years; male: 53.1%), there were 2736 in stage IIA, 2112 in IIA New, and 5622 in IIB groups. Before PSM, survival outcomes of stage IIA New patients were similar to those of stage IIA patients but better than those of stage IIB. After PSM, stage IIA New and IIB patients showed similar survival rates (OS, p = 0.276; CSS, p = 0.565). Conversely, stage IIA New patients had worse outcomes than stage IIA patients (OS, p < 0.001; CSS, p = 0.005). LASSO-based Cox analyses confirmed stage IIA New patients had inferior prognosis compared to stage IIA patients (OS HR: 1 vs. 1.325, p < 0.001; CSS HR: 1 vs. 1.327, p < 0.001). CONCLUSIONS: The downstaging of T1N1M0 patients from stage IIB to IIA in the 9th edition TNM staging remains unverified in Caucasians. Caution is warranted in assessing the staging and prognosis of these individuals. Further validation of our findings is necessary.

Complex trait susceptibilities and population diversity in a sample of 4,145 Russians.

The population of Russia consists of more than 150 local ethnicities. The ethnic diversity and geographic origins, which extend from eastern Europe to Asia, make the population uniquely positioned to investigate the shared properties of inherited disease risks between European and Asian ancestries. We present the analysis of genetic and phenotypic data from a cohort of 4,145 individuals collected in three metro areas in western Russia. We show the presence of multiple admixed genetic ancestry clusters spanning from primarily European to Asian and high identity-by-descent sharing with the Finnish population. As a result, there was notable enrichment of Finnish-specific variants in Russia. We illustrate the utility of Russian-descent cohorts for discovery of novel population-specific genetic associations, as well as replication of previously identified associations that were thought to be population-specific in other cohorts. Finally, we provide access to a database of allele frequencies and GWAS results for 464 phenotypes.

The misperception of organizational racial progress toward diversity, equity, and inclusion.

Despite a checkered racial history, people in the United States generally believe the nation has made steady, incremental progress toward achieving racial equality. In this article, we investigate whether this U.S. racial progress narrative will extend to how the workforce views the effectiveness of organizational efforts surrounding diversity, equity, and inclusion. Across three studies (N = 1,776), we test whether Black and White U.S. workers overestimate organizational racial progress in executive representation. We also examine whether these misperceptions, surrounding organizational progress, drive misunderstandings regarding the relative ineffectiveness of common organizational diversity policies. Overall, we find evidence that U.S. workers largely overestimate organizational racial progress, believe that organizational progress will naturally improve over time, and that these misperceptions of organizational racial progress may drive beliefs in the effectiveness of diversity, equity, and inclusion policies. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Trends in Black-White Differences of Antihypertensive Treatment in Individuals With and Without History of Stroke.

BACKGROUND: Recent hypertension guidelines for the general population have included race-specific recommendations for antihypertensives, whereas current stroke-specific recommendations for antihypertensives do not vary by race. The impact of these guidelines on antihypertensive regimen changes over time, and if this has varied by prevalent stroke status, is unclear. METHODS: The use of antihypertensive medications was studied cross-sectionally among self-identified Black and White participants, aged ≥45 years, with and without history of stroke, from the REGARDS study (Reasons for Geographic and Racial Differences in Stroke). Participants completed an in-home examination in 2003-2007 (visit 1) with/without an examination in 2013-2016 (visit 2). Stratified by prevalent stroke status, logistic regression mixed models examined associations between antihypertensive class use for visit 2 versus visit 1 and Black versus White individuals with an interaction adjusted for demographics, socioeconomic status, and vascular risk factors/vital signs. RESULTS: Of 17 244 stroke-free participants at visit 1, Black participants had greater adjusted odds of angiotensin-converting enzyme inhibitor usage than White participants (odds ratio [OR], 1.51 [95% CI, 1.30-1.77]). This difference was smaller in the 7476 stroke-free participants at visit 2 (OR, 1.16 [95% CI, 1.08-1.25]). In stroke-free participants at visit 1, Black participants had lower odds of calcium channel blocker (CCB) usage than White participants (OR, 0.47 [95% CI, 0.41-0.55]), but CCB usage did not differ significantly between Black and White stroke-free participants at visit 2 (OR, 1.02 [95% CI, 0.95-1.09]). Among 1437 stroke survivor participants at visit 1, Black participants had lower odds of CCB use than White participants (OR, 0.34 [95% CI, 0.26-0.45]). In 689 stroke survivor participants at visit 2, CCB use did not differ between Black and White participants (OR, 0.80 [95% CI, 0.61-1.06]). CONCLUSIONS: Racial differences in the use of guideline-recommended antihypertensives decreased between 2003-2007 and 2013-2016 in stroke-free individuals. In stroke survivors, racial differences in CCB usage narrowed over the time periods. These findings suggest there is still a mismatch between race-specific hypertension guidelines and recent clinical practice.

Anthropometry for predicting cardiometabolic disease risk factors in adolescents.

OBJECTIVE: Early screening prevents chronic diseases by identifying at-risk adolescents through anthropometric measurements, but predictive value in diverse groups is uncertain. METHODS: A cross-sectional analysis of 12- to 19-year-old individuals from the 2017-2018 National Health and Nutrition Examination Survey (NHANES) assessed the predictive ability of BMI percentile, total body fat percentage, waist circumference (WC), and waist-hip ratio (WHR) for four cardiometabolic risk factors across race and ethnicity groups using receiver operating characteristic curves. RESULTS: The unweighted sample (N = 1194; 51.2% male individuals; 23.7% Hispanic, 13.2% non-Hispanic Black [NHB], 51.1% non-Hispanic White [NHW], 12.0% other/multirace) had a weighted prevalence of elevated blood pressure of 2.7%, hyperglycemia of 36.8%, hypertriglyceridemia of 4.8%, and low high-density lipoprotein (HDL) cholesterol of 15%. WHR (area under the curve [AUC] = 0.77), WC (AUC = 0.77), and BMI percentile (AUC = 0.73) outperformed total body fat percentage (AUC = 0.56) in predicting elevated blood pressure (p < 0.001 for all). BMI percentile was more accurate than total body fat percentage in predicting hypertriglyceridemia (AUC = 0.70 vs. 0.59; p = 0.02) and low HDL cholesterol (AUC = 0.69 vs. 0.59; p < 0.001). Race and ethnicity-based predictions varied: NHW adolescents had the highest AUC (0.89; p < 0.01) for elevated blood pressure prediction compared with Hispanic and NHB adolescents (AUC = 0.77 for both). Total body fat percentage was more accurate in predicting low HDL cholesterol among Hispanic versus NHW adolescents (AUC = 0.73 vs. 0.58; p = 0.04). CONCLUSIONS: WHR, WC, and BMI percentile are better predictors of cardiometabolic risk factors in adolescents than total body fat percentage. Predictive abilities differed by race and ethnicity, highlighting the importance of tailored risk assessment strategies.

Metabolic activity of CYP2C19 and CYP2D6 on antidepressant response from 13 clinical studies using genotype imputation: a meta-analysis.

Cytochrome P450 enzymes including CYP2C19 and CYP2D6 are important for antidepressant metabolism and polymorphisms of these genes have been determined to predict metabolite levels. Nonetheless, more evidence is needed to understand the impact of genetic variations on antidepressant response. In this study, individual clinical and genetic data from 13 studies of European and East Asian ancestry populations were collected. The antidepressant response was clinically assessed as remission and percentage improvement. Imputed genotype was used to translate genetic polymorphisms to metabolic phenotypes (poor, intermediate, normal, and rapid+ultrarapid) of CYP2C19 and CYP2D6. CYP2D6 structural variants cannot be imputed from genotype data, limiting the determination of metabolic phenotypes, and precluding testing for association with response. The association of CYP2C19 metabolic phenotypes with treatment response was examined using normal metabolizers as the reference. Among 5843 depression patients, a higher remission rate was found in CYP2C19 poor metabolizers compared to normal metabolizers at nominal significance but did not survive after multiple testing correction (OR = 1.46, 95% CI [1.03, 2.06], p = 0.033, heterogeneity I2 = 0%, subgroup difference p = 0.72). No metabolic phenotype was associated with percentage improvement from baseline. After stratifying by antidepressants primarily metabolized by CYP2C19, no association was found between metabolic phenotypes and antidepressant response. Metabolic phenotypes showed differences in frequency, but not effect, between European- and East Asian-ancestry studies. In conclusion, metabolic phenotypes imputed from genetic variants using genotype were not associated with antidepressant response. CYP2C19 poor metabolizers could potentially contribute to antidepressant efficacy with more evidence needed. Sequencing and targeted pharmacogenetic testing, alongside information on side effects, antidepressant dosage, depression measures, and diverse ancestry studies, would more fully capture the influence of metabolic phenotypes.

Causal Relationships between Polyunsaturated Fatty Acids and Colon Polyps: A Two-Sample Mendelian Randomization Study.

BACKGROUND: Epidemiological studies have shown that fatty acids, especially polyunsaturated fatty acids (PUFAs), influence colorectal carcinogenesis. Colon polyps, particularly those identified as precancerous, are a frequently encountered phenomenon associated with PUFAs. However, the results are inconsistent. Therefore, we investigated the effect of PUFAs on colon polyps in individuals of European ancestry. METHODS: Single nucleotide polymorphisms correlating with PUFAs and colon polyps were derived from extensive genome-wide association studies, encompassing a discovery cohort of 135,006 samples and a corresponding validation set with 114,999 samples. Causality was assessed by employing a range of techniques, such as inverse variance weighted (IVW), weighted median, MR-Egger, and simple and weighted modes. The analysis was complemented with sensitivity checks using leave-one-out and heterogeneity evaluation through MR-IVW and Cochran's Q. RESULTS: A thorough analysis was performed to examine the causal effects of PUFAs on the development of colon polyps. The findings indicated that levels of Omega-3 fatty acids (OR = 1.0014, 95% CI 1.0004-1.0024, p = 0.004), the ratio of Docosahexaenoic acid (DHA)/total fatty acids (FAs) (DHA/totalFA; OR = 1.0015, 95% CI 1.0002-1.0028, p = 0.023), and the ratio of Omega-3/totalFA (Omega-3/totalFA; OR = 1.0013, 95% CI 1.0003-1.0022, p = 0.010) were identified as biomarkers associated with an increased risk of colon polyps. Conversely, the ratio of Omega-6/Omega-3 (OR = 0.9986, 95% CI 0.9976-0.9995, p = 0.003) and the ratio of Linoleic acid (LA)/totalFA (LA/totalFA; OR = 0.9981, 95% CI 0.9962-0.9999, p = 0.044) were negatively associated with susceptibility to colon polyps. The MR-Egger and MR-IVW analysis revealed that pleiotropy and heterogeneity did not significantly impact the outcomes. CONCLUSION: This study has uncovered a possible adverse effect of PUFAs, notably Omega-3, on the formation of colon polyps. Elevated Omega-3 levels were correlated with a heightened risk of colon polyps.

Associations between modifiable risk factors and hepatocellular carcinoma: a trans-ancestry Mendelian randomization study.

BACKGROUND: Potentially modifiable risk factors for hepatocellular carcinoma (HCC) have been investigated in observational epidemiology studies in East Asian and European populations, whereas the causal associations of most of these risk factors remain unclear. METHODS: We collected genome-wide association summary statistics of 22 modifiable risk factors in East Asians and 33 risk factors in Europeans. Genetic summary statistics of HCC were sourced from the Biobank Japan study (1,866 cases and 195,745 controls) for East Asians, and the deCODE genetics study (406 cases and 49,302 controls) and the UK Biobank (168 cases and 372 016 controls) for Europeans. Two-sample Mendelian randomization (MR) analyses were performed independently for East Asian and European populations. RESULTS: In East Asians, genetically predicted alcohol frequency, ever drinkers, aspartate aminotransferase (AST), hypothyroidism, chronic hepatitis B, and chronic hepatitis C, metabolic dysfunction-associated steatotic liver disease (MASLD), and autoimmune hepatitis were significantly associated with an increased HCC risk (P < 0.05/22). Among European population, alanine transaminase, AST, MASLD, percent liver fat, and liver iron content were significantly associated with a higher risk of HCC (P < 0.05/33). The replication dataset and meta-analysis further confirmed these results. CONCLUSIONS: Although East Asian and European populations have different factors for HCC, their common modifiable risk factors AST and MASLD for HCC, offer valuable insights for targeted intervention strategies to mitigate society burden of HCC.