Exploring the Use of Artificial Intelligence and Robotics in Prostate Cancer Management.

Integrating artificial intelligence (AI) and robotics in prostate cancer (PCa) offers a game-changing breakthrough with far-reaching implications for diagnosis, treatment, and research. AI-driven algorithms have tremendous promise for assisting early diagnosis by analyzing invisible trends within medical imaging devices such as MRI and ultrasounds. In addition, by evaluating big datasets containing patient data, genetic attributes, and treatment outcomes, these AI algorithms offer the possibility of allowing individualized treatment regimens. This ability to personalize actions to specific patients might improve therapy efficacy while reducing side effects. Robotics can increase accuracy in less invasive surgery, revolutionize therapies like prostatectomies, and improve recovery time for patients. Robotic-assisted procedures provide clinicians with remarkable skills and flexibility, allowing clinicians to negotiate complicated anatomical structures more precisely. However, the symbiotic combination of AI and robotics has several drawbacks. Concerns about data privacy, algorithm biases, and the need to continually assess AI's diagnostic proficiency offer significant hurdles. To ensure patient privacy and data security, the ethical and regulatory aspects of integrating AI and robotics require proper attention. However, combining AI and robotics opens up a galaxy of possibilities. The joint use of AI and robotics can potentially speed up drug development procedures by filtering through massive databases, resulting in the identification of new medicinal compounds. Furthermore, combining AI and robotics might usher in an innovative era of personalized medicine, allowing healthcare providers to design therapies based on detailed patient profiles. The merging of AI and robotics in PCa care gives up unprecedented prospects. While limitations highlight the necessity for caution, the possibilities of better diagnostics, tailored therapies, and new research pathways highlight the transformational abilities of AI and robotics in determining the future of PCa management. This study explores the limitations and opportunities presented by using AI and robotics in the context of PCa.

Florida-California Cancer Research, Education and Engagement (CaRE2) Health Equity Center: Structure, Innovations, and Initial Outcomes.

INTRODUCTION: The Florida-California Cancer Research, Education, and Engagement (CaRE2) Health Equity Center is a triad partnership committed to increasing institutional capacity for cancer disparity research, the diversity of the cancer workforce, and community empowerment. This article provides an overview of the structure, process innovations, and initial outcomes from the first 4 years of the CaRE2 triad partnership. METHODS: CaRE2 serves diverse populations in Florida and California using a "molecule to the community and back" model. We prioritize research on the complex intersection of biological, environmental, and social determinants health, working together with scientific and health disparities communities, sharing expertise across institutions, bidirectional training, and community outreach. Partnership progress and outcomes were assessed using mixed methods and four Program Steering Committee meetings. RESULTS: Research capacity was increased through development of a Living Repository of 81 cancer model systems from minority patients for novel cancer drug development. CaRE2 funded 15 scientific projects resulting in 38 publications. Workforce diversity entailed supporting 94 cancer trainees (92 URM) and 34 ESIs (32 URM) who coauthored 313 CaRE2-related publications and received 48 grants. Community empowerment was promoted via outreaching to more than 3000 individuals, training 145 community cancer advocates (including 28 Community Scientist Advocates), and publishing 10 community reports. CaRE2 members and trainees together have published 639 articles, received 61 grants, and 57 awards. CONCLUSION: The CaRE2 partnership has achieved its initial aims. Infrastructure for translational cancer research was expanded at one partner institution, and cancer disparities research was expanded at the two cancer centers.

Breastfeeding among Hispanic and Black Women: Barriers and Support.

We describe barriers and supports for the practice of breastfeeding, with particular focus on Black and Hispanic women in the United States. We note that breastfeeding patterns reported by WIC agencies is highly variable across the country and within states. The global campaign to support breastfeeding, Baby Friendly Hospital Initiative, and its implementation in the US is described, as well as Healthy People goals and the mixture of policies across the US that provide incomplete support for breastfeeding mothers.

Disparities in Infant Nutrition: WIC Participation and Rates of Breastfeeding in Florida.

Being cognizant of the pronounced health advantages of breastfeeding for both the nursing mother and her infant, the breastfeeding dyad, we examined breastfeeding rates among Floridian women who gave birth from 2012 to 2014 (N = 639,052). We investigated the associations between breastfeeding initiation and WIC-based breastfeeding support (the Special Supplemental Nutrition Program for Women, Infants, and Children), education level, and race and ethnicity. We compared the percentage of breastfeeding mothers between those in the WIC program and those who were not, and we compared breastfeeding rates across racial and ethnic groups. Consistent with previous reports, black newborns in this study were breastfed at lower rates than other racial groups, and WIC program participants were less likely to breastfeed than non-WIC program participants. However, by breaking down the data by education level and race, and ethnicity, we see a significantly increased rate of breastfeeding due to WIC participation for both Hispanic and black women with less than a high school education. Further, we assessed differences by insurance type, race, and WIC participation. In multivariable logistic regression, we showed that the WIC program has a significant positive impact on breastfeeding rates for all but white non-Hispanic mothers, independent of sociodemographic and geographic variables. We also note a trend of increasing breastfeeding rates over the study period (p-value < 0.0001), which has positive public health implications.

Genomic, epigenomic, and transcriptomic signatures of prostate cancer between African American and European American patients.

Prostate cancer is the second most common cancer in men in the United States, and racial disparities are greatly observed in the disease. Specifically, African American (AA) patients have 60% higher incidence and mortality rates, in addition to higher grade and stage prostate tumors, than European American (EA) patients. In order to narrow the gap between clinical outcomes for these two populations, genetic and molecular signatures contributing to this disparity have been characterized. Over the past decade, profiles of prostate tumor samples from different ethnic groups have been developed using molecular and functional assays coupled with next generation sequencing or microarrays. Comparative genome-wide analyses of genomic, epigenomic, and transcriptomic profiles from prostate tumor samples have uncovered potential race-specific mutations, copy number alterations, DNA methylation, and gene expression patterns. In this study, we reviewed over 20 published studies that examined the aforementioned molecular contributions to racial disparities in AA and EA prostate cancer patients. The reviewed genomic studies revealed mutations, deletions, amplifications, duplications, or fusion genes differentially enriched in AA patients relative to EA patients. Commonly reported genomic alterations included mutations or copy number alterations of FOXA1, KMT2D, SPOP, MYC, PTEN, TP53, ZFHX3, and the TMPRSS2-ERG fusion. The reviewed epigenomic studies identified that CpG sites near the promoters of PMEPA1, RARB, SNRPN, and TIMP3 genes were differentially methylated between AA and EA patients. Lastly, the reviewed transcriptomic studies identified genes (e.g. CCL4, CHRM3, CRYBB2, CXCR4, GALR1, GSTM3, SPINK1) and signaling pathways dysregulated between AA and EA patients. The most frequently found dysregulated pathways were involved in immune and inflammatory responses and neuroactive ligand signaling. Overall, we observed that the genomic, epigenomic, and transcriptomic alterations evaluated between AA and EA prostate cancer patients varied between studies, highlighting the impact of using different methods and sample sizes. The reported genomic, epigenomic, and transcriptomic alterations do not only uncover molecular mechanisms of tumorigenesis but also provide researchers and clinicians valuable resources to identify novel biomarkers and treatment modalities to improve the disparity of clinical outcomes between AA and EA patients.

The Use of Five Public Health Themes in Understanding the Roles of Misinformation and Education Toward Disparities in Racial and Ethnic Distribution of COVID-19.

The distribution of coronavirus disease 2019 (COVID-19) infection across the historically marginalized populations in the United States (US) has consistently been inequitable. In addition, systemic racism and prejudice, which have existed for decades, have caused a lack of faith in public health and medical experts and have resulted in the epidemic of misinformation. To counteract the COVID-19 pandemic and widespread misinformation, the political establishment and public health experts must work collaboratively. And because they are closely associated, there had been a significant increase in the prevalence of the disease as well as a spike in the number of hospitalizations and fatalities. Public health professionals have investigated a number of epidemiological strategies to stop the spread of the virus and mitigate its effects, but false information released via various media sources has caused serious harm to a number of people. To create the framework and guidelines for protecting audiences from lies and deceit, and eradicating false information before taking root in society, it is essential to understand the types of misinformation that are being spread since the disadvantaged and uneducated communities suffer disproportionately as a result. According to studies, spreading false information could have a negative impact on a country's health outcomes, as well as its economic and social well-being, if not immediately refuted. Public health themes, such as evidence-based programs, health communication, and health policy, among others need to be evaluated and put into action in order to prevent the dissemination of incorrect information. This review examines a number of public health themes, such as policy and evidence-based strategies that might help in the fight against misinformation that has wreaked havoc on families and communities, particularly the underserved and uninformed populations.

The Potential Effects of Implementing an Antibiotic Stewardship Program by Integrating It with Medication Therapy Service in a Low-Income Serving Clinic - A Single-Center Experience.

Background: Bacterial antimicrobial resistance (AMR) is a leading cause of mortality worldwide. Although AMR is common in low-income communities, there is limited evidence of the effect of antibiotic stewardship programs in low-income communities in the United States. Objectives: Our goal is to assess the effects of implementing pharmacist-led ASP by integrating it with medication therapy management service (MTM) in a low-income serving clinic. We evaluated the following 1) antibiotic prescriptions per 1000 patients, 2) the frequency of clinic (office) visits 30-day post-index clinic visits for recurring infections. Methods: To achieve our goal, we conducted a pre-post, quasi-experimental intervention study using an interrupted time-series analysis to assess the following: 1) antibiotic prescriptions per 1000 patients and the 2) frequency of office visits (including telehealth) within 30-day post-index clinic visits associated with recurrent infection. Results: Our findings revealed that the long-term effect of our antibiotic stewardship program intervention was associated with 63.69% reduction in antibiotic prescriptions per 1000 patients (change in slope = -0.173, [95% CI: (-0.30, -0.05)], P < 0.007) and a reduction in the frequency of office visits within 30-day post-index clinic visits by 67.27% (change in slope = -2.043, [95% CI: (-3.84, -0.24)], P < 0.028). Conclusion: Implementing antibiotic stewardship programs is feasible for clinics serving low-income populations. It was associated with a reduction in antibiotic prescriptions and preventable clinic (office) visits within 30 days due to infection recurrence.

HIV/AIDS Knowledge of Undergraduate Students at a Historically Black College and University.

OBJECTIVE: This study among 400 undergraduate students enrolled at Jackson State University (JSU) study aimed to assess knowledge about HIV and AIDS among African-American undergraduate students attending a historically black college and university. A cross-sectional survey was conducted. Data were collected using a validated, self-administered, and standardized questionnaire on knowledge regarding risks for HIV and AIDS. Three hundred and eighty-six students (96.5%) had good knowledge about HIV and AIDS, although some participants had misconceptions about the modes of HIV infection transmission. There were no significant gender differences for HIV and AIDS knowledge among the participants (χ² = 3.05; P = 0.08). In general we concluded that JSU undergraduate students had adequate knowledge about HIV transmission modes and AIDS, although some participants had misconceptions about the routes of HIV infection transmission. Hence, this study calls for strengthening HIV and AIDS awareness education among undergraduate students.

Using Social Cognitive Theory to Predict Medication Compliance Behavior in Patients with Depression in Southern United States in 2016 in a Cross-Sectional Study.

Introduction: Depression is a major public health issue. One of the concerns in depression research and practice pertains to non-compliance to prescribed medications. The purpose of the study was to predict compliance with medication use for patients with depression using social cognitive theory (SCT). Based on this study it was envisaged that recommendations for interventions to enhance compliance for medication use could be developed for patients with depression. Methods: The study was conducted using cross sectional design (n=148) in southern United States with a convenience sample of clinic-based depression patients with a 37-item valid and reliable questionnaire. Sample size was calculated to be 148 using G*Power (five predictors with a 0.80 power at the 0.05 alpha level and an estimated effect size of 0.10 with an inflation by 10% for missing data). Social cognitive theory constructs of expectations, self-efficacy and self-efficacy in overcoming barriers, self-control, and environment were reified. Data were analyzed using multiple linear regression and multiple logistic regression analyses. Results: Self-control for taking medication for depression (P=0.04), expectations for taking medication for depression (P=0.025), age (P<0.0001) and race (P=0.04) were significantly related to intent for taking medication for depression (Adjusted R2 = 0.183). In race, Blacks had lower intent to take medication for depression. Conclusion: Social cognitive theory is weakly predictive with low explained variance for taking medication for depression. It needs to be bolstered by newer theories like integrative model or multi-theory model of health behavior change for designing educational interventions aimed at enhancing compliance to medication for depression.

Using the PRECEDE-PROCEED model for an online peer-to-peer suicide prevention and awareness for depression (SPAD) intervention among African American college students: experimental study.

Background: Suicide rates are high among African American students because they are at a greater risk of depression. A commonly used suicide prevention approach is the gatekeeper training. However, gatekeeper training is neither evidence-based nor has it been identified as culturally-appropriate for African American college students. Therefore, the purpose of this study was to develop and evaluate an online peer-to-peer PRECEDE-PROCEED model based depression awareness and suicide prevention program that was culturally appropriate for African American college students. Methods: The setting was a predominantly Black institution in southern USA. A pre-experimental repeated measures one group design was used to measure changes in peer educators' (n = 29) predisposing factors regarding knowledge, skills and attitudes pertaining to depression, reinforcing factors or receiving support from peers, healthcare professionals and teachers to help someone with depression, enabling factors or sureness of finding organizations to help someone with depression, and behavior for helping someone with depression at pretest, posttest and 1-month follow-up. A posttest only one group design was also used to measure effect on predisposing factors and behavior of students (n = 300) trained by peer educators. Results: There were statistically significant improvements in attitudes related to depression as disease (P = 0.003; η2 = 0.39), attitudes about managing depression (P = 0.0001; η2 = 0.30), skills(P = 0.0001; η2 = 0.41), reinforcing factors (P = 0.018; η2 = 0.13), enabling factors (P = 0.0001;η2 = 0.31), and behavior (P = 0.016; η2 = 0.14). Changes in knowledge about depression and attitudes about helping people with depression were not statistically significant over time for peer educators. The peer-to-peer training was not completely effective in transferring corresponding changes for students trained by peers. Conclusion: The program was effective for peer educators but peers could not significantly influence other students in all domains. This study provides a starting point toward evidencebased approaches for health promotion interventionists addressing depression awareness and suicide prevention among African American college students.

Genome-wide association study of coronary artery calcified atherosclerotic plaque in African Americans with type 2 diabetes.

BACKGROUND: Coronary artery calcified atherosclerotic plaque (CAC) predicts cardiovascular disease (CVD). Despite exposure to more severe conventional CVD risk factors, African Americans (AAs) are less likely to develop CAC, and when they do, have markedly lower levels than European Americans. Genetic factors likely contribute to the observed ethnic differences. To identify genes associated with CAC in AAs with type 2 diabetes (T2D), a genome-wide association study (GWAS) was performed using the Illumina 5 M chip in 691 African American-Diabetes Heart Study participants (AA-DHS), with replication in 205 Jackson Heart Study (JHS) participants with T2D. Genetic association tests were performed on the genotyped and 1000 Genomes-imputed markers separately for each study, and combined in a meta-analysis. RESULTS: Single nucleotide polymorphisms (SNPs), rs11353135 (2q22.1), rs16879003 (6p22.3), rs5014012, rs58071836 and rs10244825 (all on chromosome 7), rs10918777 (9q31.2), rs13331874 (16p13.3) and rs4459623 (18q12.1) were associated with presence and/or quantity of CAC in the AA-DHS and JHS, with meta-analysis p-values ≤8.0 × 10-7. The strongest result in AA-DHS alone was rs6491315 in the 13q32.1 region (parameter estimate (SE) = -1.14 (0.20); p-value = 9.1 × 10-9). This GWAS peak replicated a previously reported AA-DHS CAC admixture signal (rs7492028, LOD score 2.8). CONCLUSIONS: Genetic association between SNPs on chromosomes 2, 6, 7, 9, 16 and 18 and CAC were detected in AAs with T2D from AA-DHS and replicated in the JHS. These data support a role for genetic variation on these chromosomes as contributors to CAC in AAs with T2D, as well as to variation in CAC between populations of African and European ancestry.

Fine-mapping, novel loci identification, and SNP association transferability in a genome-wide association study of QRS duration in African Americans.

The electrocardiographic QRS duration, a measure of ventricular depolarization and conduction, is associated with cardiovascular mortality. While single nucleotide polymorphisms (SNPs) associated with QRS duration have been identified at 22 loci in populations of European descent, the genetic architecture of QRS duration in non-European populations is largely unknown. We therefore performed a genome-wide association study (GWAS) meta-analysis of QRS duration in 13,031 African Americans from ten cohorts and a transethnic GWAS meta-analysis with additional results from populations of European descent. In the African American GWAS, a single genome-wide significant SNP association was identified (rs3922844, P = 4 × 10-14) in intron 16 of SCN5A, a voltage-gated cardiac sodium channel gene. The QRS-prolonging rs3922844 C allele was also associated with decreased SCN5A RNA expression in human atrial tissue (P = 1.1 × 10-4). High density genotyping revealed that the SCN5A association region in African Americans was confined to intron 16. Transethnic GWAS meta-analysis identified novel SNP associations on chromosome 18 in MYL12A (rs1662342, P = 4.9 × 10-8) and chromosome 1 near CD1E and SPTA1 (rs7547997, P = 7.9 × 10-9). The 22 QRS loci previously identified in populations of European descent were enriched for significant SNP associations with QRS duration in African Americans (P = 9.9 × 10-7), and index SNP associations in or near SCN5A, SCN10A, CDKN1A, NFIA, HAND1, TBX5 and SETBP1 replicated in African Americans. In summary, rs3922844 was associated with QRS duration and SCN5A expression, two novel QRS loci were identified using transethnic meta-analysis, and a significant proportion of QRS-SNP associations discovered in populations of European descent were transferable to African Americans when adequate power was achieved.

Common variants in DRD2 are associated with sleep duration: the CARe consortium.

Sleep duration is implicated in the etiologies of chronic diseases and premature mortality. However, the genetic basis for sleep duration is poorly defined. We sought to identify novel genetic components influencing sleep duration in a multi-ethnic sample. Meta-analyses were conducted of genetic associations with self-reported, habitual sleep duration from seven Candidate Gene Association Resource (CARe) cohorts of over 25 000 individuals of African, Asian, European and Hispanic American ancestry. All individuals were genotyped for ∼50 000 SNPs from 2000 candidate heart, lung, blood and sleep genes. African-Americans had additional genome-wide genotypes. Four cohorts provided replication. A SNP (rs17601612) in the dopamine D2 receptor gene (DRD2) was significantly associated with sleep duration (P = 9.8 × 10(-7)). Conditional analysis identified a second DRD2 signal with opposite effects on sleep duration. In exploratory analysis, suggestive association was observed for rs17601612 with polysomnographically determined sleep latency (P = 0.002). The lead DRD2 signal was recently identified in a schizophrenia GWAS, and a genetic risk score of 11 additional schizophrenia GWAS loci genotyped on the IBC array was also associated with longer sleep duration (P = 0.03). These findings support a role for DRD2 in influencing sleep duration. Our work motivates future pharmocogenetics research on alerting agents such as caffeine and modafinil that interact with the dopaminergic pathway and further investigation of genetic overlap between sleep and neuro-psychiatric traits.

Lipids, obesity and gallbladder disease in women: insights from genetic studies using the cardiovascular gene-centric 50K SNP array.

Gallbladder disease (GBD) has an overall prevalence of 10-40% depending on factors such as age, gender, population, obesity and diabetes, and represents a major economic burden. Although gallstones are composed of cholesterol by-products and are associated with obesity, presumed causal pathways remain unproven, although BMI reduction is typically recommended. We performed genetic studies to discover candidate genes and define pathways involved in GBD. We genotyped 15,241 women of European ancestry from three cohorts, including 3216 with GBD, using the Human cardiovascular disease (HumanCVD) BeadChip containing up to ~ 53,000 single-nucleotide polymorphisms (SNPs). Effect sizes with P-values for development of GBD were generated. We identify two new loci associated with GBD, GCKR rs1260326:T>C (P = 5.88 × 10(-7), ß = -0.146) and TTC39B rs686030:C>A (P = 6.95 x 10(-7), ß = 0.271) and detect four independent SNP effects in ABCG8 rs4953023:G>A (P=7.41 × 10(-47), ß = 0.734), ABCG8 rs4299376:G(>)T (P = 2.40 × 10(-18), ß = 0.278), ABCG5 rs6544718:T>C (P = 2.08 × 10(-14), ß = 0.044) and ABCG5 rs6720173:G>C (P = 3.81 × 10(-12), ß(=)0.262) in conditional analyses taking genotypes of rs4953023:G>A as a covariate. We also delineate the risk effects among many genotypes known to influence lipids. These data, from the largest GBD genetic study to date, show that specific, mainly hepatocyte-centred, components of lipid metabolism are important to GBD risk in women. We discuss the potential pharmaceutical implications of our findings.

Group Conference Call Diabetes Educational Support Sessions: A Pilot Study.

The aim of this study was to determine the acceptability of group-conference-call diabetes educational support sessions for rural dwelling southern African-American women and to describe the impact on diabetes distress. Pre- post-test design was utilized to determine any change in scores on questionnaires. Qualitative techniques were utilized to determine the acceptability of the conference callformat. Participants recruited (N = 3) manifested either dysglycemia or frank type 2 diabetes. Diabetes distress and knowledge tools, demographics, baseline laboratory data, and measures of body habitus were obtained. An adapted version of the American Association of Diabetes Educator's Association diabetes education curriculum was used to provide the classes. The conference call intervention was found to be convenient, informative, and it removed the hassle of needing to be in one location to receive education. Diabetes distress was reduced (p = 0.005) in the sub-scale related regimen management. Offering alternatives to in-person diabetes education classes has the potential to reduce levels of opportunity costs and include a larger number of individuals living chaotic lives due to the demands of chronic illness and extended family needs.

HMG-coenzyme A reductase inhibition, type 2 diabetes, and bodyweight: evidence from genetic analysis and randomised trials.

BACKGROUND: Statins increase the risk of new-onset type 2 diabetes mellitus. We aimed to assess whether this increase in risk is a consequence of inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), the intended drug target. METHODS: We used single nucleotide polymorphisms in the HMGCR gene, rs17238484 (for the main analysis) and rs12916 (for a subsidiary analysis) as proxies for HMGCR inhibition by statins. We examined associations of these variants with plasma lipid, glucose, and insulin concentrations; bodyweight; waist circumference; and prevalent and incident type 2 diabetes. Study-specific effect estimates per copy of each LDL-lowering allele were pooled by meta-analysis. These findings were compared with a meta-analysis of new-onset type 2 diabetes and bodyweight change data from randomised trials of statin drugs. The effects of statins in each randomised trial were assessed using meta-analysis. FINDINGS: Data were available for up to 223 463 individuals from 43 genetic studies. Each additional rs17238484-G allele was associated with a mean 0·06 mmol/L (95% CI 0·05-0·07) lower LDL cholesterol and higher body weight (0·30 kg, 0·18-0·43), waist circumference (0·32 cm, 0·16-0·47), plasma insulin concentration (1·62%, 0·53-2·72), and plasma glucose concentration (0·23%, 0·02-0·44). The rs12916 SNP had similar effects on LDL cholesterol, bodyweight, and waist circumference. The rs17238484-G allele seemed to be associated with higher risk of type 2 diabetes (odds ratio [OR] per allele 1·02, 95% CI 1·00-1·05); the rs12916-T allele association was consistent (1·06, 1·03-1·09). In 129 170 individuals in randomised trials, statins lowered LDL cholesterol by 0·92 mmol/L (95% CI 0·18-1·67) at 1-year of follow-up, increased bodyweight by 0·24 kg (95% CI 0·10-0·38 in all trials; 0·33 kg, 95% CI 0·24-0·42 in placebo or standard care controlled trials and -0·15 kg, 95% CI -0·39 to 0·08 in intensive-dose vs moderate-dose trials) at a mean of 4·2 years (range 1·9-6·7) of follow-up, and increased the odds of new-onset type 2 diabetes (OR 1·12, 95% CI 1·06-1·18 in all trials; 1·11, 95% CI 1·03-1·20 in placebo or standard care controlled trials and 1·12, 95% CI 1·04-1·22 in intensive-dose vs moderate dose trials). INTERPRETATION: The increased risk of type 2 diabetes noted with statins is at least partially explained by HMGCR inhibition. FUNDING: The funding sources are cited at the end of the paper.

Associations of adiponectin with individual European ancestry in African Americans: the Jackson Heart Study.

BACKGROUND: Compared with European Americans, African Americans (AAs) exhibit lower levels of the cardio-metabolically protective adiponectin even after accounting for adiposity measures. Because few studies have examined in AA the association between adiponectin and genetic admixture, a dense panel of ancestry informative markers (AIMs) was used to estimate the individual proportions of European ancestry (PEA) for the AAs enrolled in a large community-based cohort, the Jackson Heart Study (JHS). We tested the hypothesis that plasma adiponectin and PEA are directly associated and assessed the interaction with a series of cardio-metabolic risk factors. METHODS: Plasma specimens from 1439 JHS participants were analyzed by ELISA for adiponectin levels. Using pseudo-ancestral population genotype data from the HapMap Consortium, PEA was estimated with a panel of up to 1447 genome-wide preselected AIMs by a maximum likelihood approach. Interaction assessment, stepwise linear and cubic multivariable-adjusted regression models were used to analyze the cross-sectional association between adiponectin and PEA. RESULTS: Among the study participants (62% women; mean age 48 ± 12 years), the median (interquartile range) of PEA was 15.8 (9.3)%. Body mass index (BMI) (p = 0.04) and insulin resistance (p = 0.0001) modified the association between adiponectin and PEA. Adiponectin was directly and linearly associated with PEA (ß = 0.62 ± 0.28, p = 0.03) among non-obese (n = 673) and insulin sensitive participants (n = 1141; ß = 0.74 ± 0.23, p = 0.001), but not among those obese or with insulin resistance. No threshold point effect was detected for non-obese participants. CONCLUSIONS: In a large AA population, the individual proportion of European ancestry was linearly and directly associated with plasma adiponectin among non-obese and non insulin-resistant participants, pointing to the interaction of genetic and metabolic factors influencing adiponectin levels.

Mendelian randomization studies do not support a causal role for reduced circulating adiponectin levels in insulin resistance and type 2 diabetes.

Adiponectin is strongly inversely associated with insulin resistance and type 2 diabetes, but its causal role remains controversial. We used a Mendelian randomization approach to test the hypothesis that adiponectin causally influences insulin resistance and type 2 diabetes. We used genetic variants at the ADIPOQ gene as instruments to calculate a regression slope between adiponectin levels and metabolic traits (up to 31,000 individuals) and a combination of instrumental variables and summary statistics-based genetic risk scores to test the associations with gold-standard measures of insulin sensitivity (2,969 individuals) and type 2 diabetes (15,960 case subjects and 64,731 control subjects). In conventional regression analyses, a 1-SD decrease in adiponectin levels was correlated with a 0.31-SD (95% CI 0.26-0.35) increase in fasting insulin, a 0.34-SD (0.30-0.38) decrease in insulin sensitivity, and a type 2 diabetes odds ratio (OR) of 1.75 (1.47-2.13). The instrumental variable analysis revealed no evidence of a causal association between genetically lower circulating adiponectin and higher fasting insulin (0.02 SD; 95% CI -0.07 to 0.11; N = 29,771), nominal evidence of a causal relationship with lower insulin sensitivity (-0.20 SD; 95% CI -0.38 to -0.02; N = 1,860), and no evidence of a relationship with type 2 diabetes (OR 0.94; 95% CI 0.75-1.19; N = 2,777 case subjects and 13,011 control subjects). Using the ADIPOQ summary statistics genetic risk scores, we found no evidence of an association between adiponectin-lowering alleles and insulin sensitivity (effect per weighted adiponectin-lowering allele: -0.03 SD; 95% CI -0.07 to 0.01; N = 2,969) or type 2 diabetes (OR per weighted adiponectin-lowering allele: 0.99; 95% CI 0.95-1.04; 15,960 case subjects vs. 64,731 control subjects). These results do not provide any consistent evidence that interventions aimed at increasing adiponectin levels will improve insulin sensitivity or risk of type 2 diabetes.

Interactive influences of ethnicity, endothelin-1 gene, and everyday discrimination upon nocturnal ambulatory blood pressure.

BACKGROUND: Everyday discrimination scale scores are associated with increased ambulatory blood pressure (BP) and reduced nocturnal dipping, and the endothelin-1 (ET-1)/Lys198Asn polymorphism is associated with increased resting BP and exaggerated BP reactivity among African Americans compared to European Americans. Combined influences of these factors on BP control are unknown. PURPOSE: This study tested the hypothesis of a three-way interaction between ethnicity, ET-1 carrier status, and everyday discrimination upon ambulatory BP and nocturnal dipping. METHODS: Baseline laboratory anthropometrics and the everyday discrimination scale were completed by 352 (175 African American) young adult normotensives, followed by 24-h ambulatory BP monitoring. RESULTS: For nocturnal dipping, multiple regression models controlling for age, sex, ethnicity, and body mass index revealed significant three-way ET-1 × everyday discrimination × ethnicity interactions. Specifically, among African American ET-1 T-allele carriers, increases in everyday discrimination led to reduced nocturnal dipping. CONCLUSIONS: African Americans that carry the ET-1/Lys198Asn T-allele and report higher everyday discrimination scores may be at particular risk for reduced nocturnal dipping.

Genetic analysis of a population heavy drinking phenotype identifies risk variants in whites.

Genetic association studies thus far have used detailed diagnoses of alcoholism to identify loci associated with risk. This proof-of-concept analysis examined whether population data of lifetime heaviest alcohol consumption may be used to identify genetic loci that modulate risk. We conducted a genetic association study in European Americans between variants in approximately 2100 genes and alcohol consumption as part of the Candidate gene Association Resource project. We defined cases as individuals with a history of drinking 5 or more drinks per day almost every day of the week and controls as current light drinkers (1-5 drinks per week). We cross-validated identified single nucleotide polymorphisms in a meta-analysis of 2 cohorts of unrelated individuals--Atherosclerosis Risk in Communities (ARIC) and Cardiovascular Health Study (CHS)--and in a separate cohort of related individuals--Framingham Heart Study (FHS). The most significant variant in the meta-analysis of ARIC and CHS was rs6933598 in methylenetetrahydrofolate dehydrogenase (P = 7.46 × 10(-05)) with a P value in FHS of 0.042. The top variants in FHS were rs12249562 in cubulin (P = 3.03 × 10(-05)) and rs9839267 near cholecystokinin (P = 3.05 × 10(-05)) with a P value of 0.019 for rs9839267 in CHS. We have here shown feasibility in evaluating lifetime incidence of heavy alcohol drinking from population-based studies for the purpose of conducting genetic association analyses.