Red meat intake interacts with a TGF-β-pathway-based polygenic risk score to impact colorectal cancer risk: Application of a novel approach for polygenic risk score construction.

Background: High intake of red and/or processed meat are established colorectal cancer (CRC) risk factors. Genome-wide association studies (GWAS) have reported 204 variants (G) associated with CRC risk. We used functional annotation data to identify subsets of variants within known pathways and constructed pathway-based Polygenic Risk Scores (pPRS) to model pPRS x environment (E) interactions.

Long-Term Mortality After Cholecystectomy in a Nationwide Cohort of Swedish Individuals Between 1969 and 2016.

Background And Aims: Few studies have reported overall and subgroup long-term survival after cholecystectomy.

Methods: Linking gallbladder histopathology reports from all of Sweden's 28 pathology departments to the Swedish Patient Register, we identified 159,946 adults 20-79 years of age with incident cholecystectomy between 1969 and 2016. Each patient was age- and sex- matched to 5 general population reference individuals (N = 764,681).

Smoking, alcohol and risk of sarcopenia: a Mendelian randomisation study.

Objective: Observational studies have found that cigarette smoking increased the prevalence and incidence of sarcopenia, whereas alcohol consumption appeared to decrease the risk. These findings, however, may be susceptible to either confounding bias or reverse causation. We conducted a Mendelian randomisation (MR) study to appraise the causal relation of cigarette smoking and alcohol consumption to the risk of sarcopenia.

Novel metabolomic predictors of incident colorectal cancer in men and women.

Background: Metabolomic profiles may influence colorectal cancer (CRC) development. Few studies have performed prediagnostic metabolome-wide analyses with CRC risk.

Methods: We conducted a nested case-control study among women (Nurses' Health Study) and men (Health Professionals Follow-Up Study) who provided blood between 1989 and 1995.

Prediagnostic Amino Acid Metabolites and Risk of Gout, Accounting for Serum Urate: Prospective Cohort Study and Mendelian Randomization.

Objective: Our objective was to prospectively investigate prediagnostic population-based metabolome for risk of hospitalized gout (ie, most accurate, severe, and costly cases), accounting for serum urate.

Methods: We conducted prediagnostic metabolome-wide analyses among 249,677 UK Biobank participants with nuclear magnetic resonance metabolomic profiling (N = 168 metabolites, including eight amino acids) from baseline blood samples (2006-2010) without a history of gout. We calculated multivariable hazard ratios (HRs) for hospitalized incident gout, before and after adjusting for serum urate levels; we included patients with nonhospitalized incident gout in a sensitivity analysis.

Fine-mapping analysis including over 254,000 East Asian and European descendants identifies 136 putative colorectal cancer susceptibility genes.

Genome-wide association studies (GWAS) have identified more than 200 common genetic variants independently associated with colorectal cancer (CRC) risk, but the causal variants and target genes are mostly unknown. We sought to fine-map all known CRC risk loci using GWAS data from 100,204 cases and 154,587 controls of East Asian and European ancestry. Our stepwise conditional analyses revealed 238 independent association signals of CRC risk, each with a set of credible causal variants (CCVs), of which 28 signals had a single CCV.

Germline genetic regulation of the colorectal tumor immune microenvironment.

Objective: To evaluate the contribution of germline genetics to regulating the briskness and diversity of T cell responses in CRC, we conducted a genome-wide association study to examine the associations between germline genetic variation and quantitative measures of T cell landscapes in 2,876 colorectal tumors from participants in the Molecular Epidemiology of Colorectal Cancer Study (MECC).

Methods: Germline DNA samples were genotyped and imputed using genome-wide arrays. Tumor DNA samples were extracted from paraffin blocks, and T cell receptor clonality and abundance were quantified by immunoSEQ (Adaptive Biotechnologies, Seattle, WA).

Serum Urate and Recurrent Gout.

Importance: Approximately 12 million adults in the US have a history of gout, but whether serum urate levels can help predict recurrence is unclear.

Objective: To assess associations of a single serum urate measurement with subsequent risk of acute gout flares and subsequent risk of hospitalizations for gout among patients in the UK with a history of gout.

Design, Setting, And Participants: This retrospective study included patients with a history of gout identified from the UK between 2006 and 2010 who were followed up through Primary Care Linked Data medical record linkage until 2017 and through the Hospital Episode Statistics database until 2020.

Application of Mendelian randomization to explore the causal role of the human gut microbiome in colorectal cancer.

The role of the human gut microbiome in colorectal cancer (CRC) is unclear as most studies on the topic are unable to discern correlation from causation. We apply two-sample Mendelian randomization (MR) to estimate the causal relationship between the gut microbiome and CRC. We used summary-level data from independent genome-wide association studies to estimate the causal effect of 14 microbial traits (n = 3890 individuals) on overall CRC (55,168 cases, 65,160 controls) and site-specific CRC risk, conducting several sensitivity analyses to understand the nature of results.

Prediagnostic Glycoprotein Acetyl Levels and Incident and Recurrent Flare Risk Accounting for Serum Urate Levels: A Population-Based, Prospective Study and Mendelian Randomization Analysis.

Objective: To prospectively investigate population-based metabolomics for incident gout and reproduce the findings for recurrent flares, accounting for serum urate.

Methods: We conducted a prediagnostic metabolome-wide analysis among 105,615 UK Biobank participants with nuclear magnetic resonance metabolomic profiling data (168 total metabolites) from baseline blood samples collected 2006-2010 in those without history of gout. We calculated hazard ratios (HRs) for incident gout, adjusted for gout risk factors, excluding and including serum urate levels, overall and according to fasting duration before sample collection.

Interactions Between Genetic Risk and Diet Influencing Risk of Incident Female Gout: Discovery and Replication Analysis of Four Prospective Cohorts.

Objective: To examine whether the cross-sectional gene-diet interaction for prevalent hyperuricemia among women translates prospectively to risk of incident female gout.

Methods: We analyzed the interaction between genetic predisposition and adherence to a healthy dietary pattern (i.e.

Nationwide racial/ethnic disparities in US emergency department visits and hospitalizations for gout.

Objectives: Gout prevalence is reportedly ∼20% higher in US Black adults than Whites, but racial differences in emergency department (ED) visits and hospitalizations for gout are unknown. We evaluated the latest US national utilization datasets according to racial/ethnic groups.

Methods: Using 2019 US National Emergency Department Sample and National Inpatient Sample databases, we compared racial/ethnic differences in annual population rates of ED visits and hospitalizations for gout (primary discharge diagnosis) per 100 000 US adults (using 2019 age- and sex-specific US census data).

Racial and Sex Disparities in Gout Prevalence Among US Adults.

Importance: Emerging data suggest gout and hyperuricemia may now be more frequent among Black adults in the US than White adults, especially Black women. However, national-level, sex-specific general population data on racial differences in gout prevalence and potential socioclinical risk factors are lacking.

Objective: To identify sex-specific factors driving disparities between Black and White adults in contemporary gout prevalence in the US general population.

The mental health burden of racial and ethnic minorities during the COVID-19 pandemic.

Racial/ethnic minorities have been disproportionately impacted by COVID-19. The effects of COVID-19 on the long-term mental health of minorities remains unclear. To evaluate differences in odds of screening positive for depression and anxiety among various racial and ethnic groups during the latter phase of the COVID-19 pandemic, we performed a cross-sectional analysis of 691,473 participants nested within the prospective smartphone-based COVID Symptom Study in the United States (U.