Trans-ethnic Meta-analysis and Functional Annotation Illuminates the Genetic Architecture of Fasting Glucose and Insulin.

Knowledge of the genetic basis of the type 2 diabetes (T2D)-related quantitative traits fasting glucose (FG) and insulin (FI) in African ancestry (AA) individuals has been limited. In non-diabetic subjects of AA (n = 20,209) and European ancestry (EA; n = 57,292), we performed trans-ethnic (AA+EA) fine-mapping of 54 established EA FG or FI loci with detailed functional annotation, assessed their relevance in AA individuals, and sought previously undescribed loci through trans-ethnic (AA+EA) meta-analysis. We narrowed credible sets of variants driving association signals for 22/54 EA-associated loci; 18/22 credible sets overlapped with active islet-specific enhancers or transcription factor (TF) binding sites, and 21/22 contained at least one TF motif. Of the 54 EA-associated loci, 23 were shared between EA and AA. Replication with an additional 10,096 AA individuals identified two previously undescribed FI loci, chrX FAM133A (rs213676) and chr5 PELO (rs6450057). Trans-ethnic analyses with regulatory annotation illuminate the genetic architecture of glycemic traits and suggest gene regulation as a target to advance precision medicine for T2D. Our approach to utilize state-of-the-art functional annotation and implement trans-ethnic association analysis for discovery and fine-mapping offers a framework for further follow-up and characterization of GWAS signals of complex trait loci.

Racial and Ethnic Disparities in Patients With Inflammatory Bowel Disease: An Online Survey.

BACKGROUND: Data regarding care access and outcomes in Black/Indigenous/People of Color/Hispanic (BIPOC/H) individuals is limited. This study evaluated care barriers, disease status, and outcomes among a diverse population of White/non-Hispanic (W/NH) and BIPOC/H inflammatory bowel disease (IBD) patients at a large U.S. health system. METHODS: An anonymous online survey was administered to adult IBD patients at Ochsner Health treated between Aug 2019 and Dec 2021. Collected data included symptoms, the Consumer Assessment of Healthcare Providers and Systems and Barriers to Care surveys, health-related quality of life (HRQOL) via the Short Inflammatory Bowel Disease Questionnaire, the Medication Adherence Rating Scale-4, and the Beliefs about Medicines Questionnaire. Medical record data examined healthcare resource utilization. Analyses compared W/NH and BIPOC/H via chi-square and t tests. RESULTS: Compared with their W/NH counterparts, BIPOC/H patients reported more difficulties accessing IBD specialists (26% vs 11%; P = .03), poor symptom control (35% vs 18%; P = .02), lower mean HRQOL (41 ± 14 vs 49 ± 13; P < .001), more negative impact on employment (50% vs 33%; P = .029), worse financial stability (53% vs 32%; P = .006), and more problems finding social/emotional support for IBD (64% vs 37%; P < .001). BIPOC/H patients utilized emergency department services more often (42% vs 22%; P = .004), reported higher concern scores related to IBD medication (17.1 vs 14.9; P = .001), and worried more about medication harm (19.5% vs 17.7%; P = .002). The survey response rate was 14%. CONCLUSIONS: BIPOC/H patients with IBD had worse clinical disease, lower HRQOL scores, had more medication concerns, had less access to specialists, had less social and emotional support, and used emergency department services more often than W/NH patients.

This study examined care access and outcomes in a diverse population of inflammatory bowel disease patients, comparing White/non-Hispanic and Black/Indigenous/People of Color/Hispanic individuals. The analysis revealed that Black/Indigenous/People of Color/Hispanic patients reported greater difficulties accessing inflammatory bowel disease specialists, poorer symptom control, and lower quality of life, and faced challenges in employment, financial stability, and finding social/emotional support. Additionally, they utilized emergency department services more frequently, expressed higher medication concerns, and had increased worries about medication harm.

Relative efficiency and sample size for cluster randomized trials with variable cluster sizes.

BACKGROUND: The statistical power of cluster randomized trials depends on two sample size components, the number of clusters per group and the numbers of individuals within clusters (cluster size). Variable cluster sizes are common and this variation alone may have significant impact on study power. Previous approaches have taken this into account by either adjusting total sample size using a designated design effect or adjusting the number of clusters according to an assessment of the relative efficiency of unequal versus equal cluster sizes. PURPOSE: This article defines a relative efficiency of unequal versus equal cluster sizes using noncentrality parameters, investigates properties of this measure, and proposes an approach for adjusting the required sample size accordingly. METHODS: We focus on comparing two groups with normally distributed outcomes using t-test, and use the noncentrality parameter to define the relative efficiency of unequal versus equal cluster sizes and show that statistical power depends only on this parameter for a given number of clusters. We calculate the sample size required for an unequal cluster sizes trial to have the same power as one with equal cluster sizes. RESULTS: Relative efficiency based on the noncentrality parameter is straightforward to calculate and easy to interpret. It connects the required mean cluster size directly to the required sample size with equal cluster sizes. Consequently, our approach first determines the sample size requirements with equal cluster sizes for a pre-specified study power and then calculates the required mean cluster size while keeping the number of clusters unchanged. Our approach allows adjustment in mean cluster size alone or simultaneous adjustment in mean cluster size and number of clusters, and is a flexible alternative to and a useful complement to existing methods. Comparison indicated that we have defined a relative efficiency that is greater than the relative efficiency in the literature under some conditions. LIMITATIONS: Our measure of relative efficiency might be less than the measure in the literature under some conditions, underestimating the relative efficiency. CONCLUSIONS: The relative efficiency of unequal versus equal cluster sizes defined using the noncentrality parameter suggests a sample size approach that is a flexible alternative and a useful complement to existing methods.

Some dietary and adipose tissue carotenoids are associated with the risk of nonfatal acute myocardial infarction in Costa Rica.

Antioxidants, particularly carotenoids and tocopherols, may protect against cardiovascular disease. The objective of this study was to determine whether dietary and adipose tissue carotenoids and tocopherols are associated with the risk of myocardial infarction (MI). Cases (n = 1456) of a first acute MI were identified and matched by age, sex, and residence to randomly selected population controls (n = 1456) living in Costa Rica. Carotenoids and tocopherols were measured in adipose tissue using HPLC. Dietary intake was assessed using a validated FFQ. Anthropometrical and lifestyle data were collected using an interviewer-administered questionnaire. Subjects were distributed into quintiles of intake or adipose tissue concentration of carotenoids or tocopherols. The lowest quintile was used as the referent in conditional logistic regression analyses. Adipose tissue beta-carotene showed a significant inverse relation with MI risk; the odds ratio (OR) comparing the highest to the lowest quintile was 0.70 (95% CI: 0.51-0.96, P for trend = 0.02). Intake of fruits and vegetables that are rich in beta-carotene was also inversely associated with the risk of MI (OR = 0.74; CI: 0.54-1.01, P for trend = 0.09). In contrast, lutein + zeaxanthin in adipose tissue (OR = 1.46; CI: 1.05-2.05, P for trend = 0.02) and diet (OR = 1.18; CI: 0.88-1.57, P for trend = 0.02) was positively associated with MI risk. MI risk was not associated with any of the other carotenoids or tocopherols in the diet or adipose tissue. Thus, the inverse association between beta-carotene and MI risk suggests that beta-carotene protects against MI or it is a marker of some protective factor in foods containing beta-carotene. The mechanism underlying the positive association between lutein + zeaxanthin and the risk of MI warrants investigation.