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UNC-authored articles published by Frontiers
Works (762)
21. Enhancing the clinical research workforce: a collaborative approach with human resources
- Title Tesim:
- Enhancing the clinical research workforce: a collaborative approach with human resources
- Creator:
- Verble, William, Snyder, Denise C., Gaudaur, Heather, Mendell, Angela, Marchant, Mark, Gilliam, Christine, Viera, Laura, and McCubbin, Andrea
- Date of publication:
- 2024
- Abstract Tesim:
- Jobs for clinical research professionals (CRPs) have grown increasingly complex over the past 20+ years. This is due largely to additional administrative burden for investigators, study teams, sponsors, Clinical Research Organizations (CROs), and sites, particularly Academic Medical Centers (AMCs). Furthermore, National Institutes of Health (NIH) has reduced capacity to effectively fund research recognizing this is dependent on the overall congressional budget, which creates greater pressure for clinician scientists to secure external support. It is widely known clinical research will continue to become increasingly more complex for clinician scientists. This manuscript explores adoption of a clinical research competency-based job classification framework from the Joint Task Force for Clinical Trial Competency (JTFCTC) across several AMCs and the role of Human Resources (HR) in facilitating this process. This collaboration focuses on fostering successful projects tied to the business case in order to address equity and improve support for the clinical research enterprise.
- Resource type:
- Article
- Affiliation Label Tesim:
- North Carolina Translational and Clinical Sciences Institute
- DOI:
- https://doi.org/10.17615/k7p9-7r42
- Edition:
- Publisher
- Identifier:
- https://doi.org/10.3389/fphar.2024.1295155
- ISSN:
- 1663-9812
- Journal Title:
- Frontiers in Pharmacology
- Journal Volume:
- 15
- Keyword:
- clinical research professional (CRP), academic medical center (AMC), workforce development, clinical research coordinator (CRC), human resources (HR), and clinical research nurse (CRN)
- Language Label:
- English
- License Label:
- Attribution 4.0 International
- Other Affiliation:
- University of Kentucky, Duke University, University of Cincinnati, University of Alabama at Birmingham, and
- Person:
- Verble, William, Snyder, Denise C., Gaudaur, Heather, Mendell, Angela, Marchant, Mark, Gilliam, Christine, Viera, Laura, and McCubbin, Andrea
- Publisher:
- Frontiers
- Rights Statement Label:
- In Copyright
- Source:
- 11eedf24-01a6-4b2e-b0f2-18e158862a52
22. Editorial: The role of adipose tissue and resident immune cells in infections
- Title Tesim:
- Editorial: The role of adipose tissue and resident immune cells in infections
- Creator:
- Teixeira, Luzia, Whitmire, Jason K., and Bourgeois, Christine
- Date of publication:
- 2024
- Abstract Tesim:
- Adipose tissues are distributed throughout the body and are in direct contact with sites of infection entry, such as mucosal tissues, gut, and skin. There is increasing appreciation that adipose tissue can influence local and systemic immune responses to infection. The adipose tissue can modulate immune responses through changes in the expression of pro- and anti-inflammatory cytokines, adipokines, and hormones that regulate general metabolism. Immune cells within adipose show differentiation states that are distinct from those in circulation or in lymphoid tissues, suggesting that the adipose environment regulates immune cell activity. The mechanisms leading to immune cell recruitment and maintenance within adipose remain enigmatic. Changes in diet that lead to obesity can alter the frequencies of regulatory or effector cells within adipose, potentially affecting local and systemic immune protection. Obesity is associated with higher susceptibility to infections possibly due to alterations in immune cells residing in adipose tissue. The interplay between immune cells and adipose is complex and bi-directional: immune cells residing within adipose tissue can perturb adipose tissue homeostasis and whole-body metabolism and, conversely, metabolic cues can modulate immune responses. Several reports demonstrate that microorganisms can target and even persist in adipose tissues. However, relatively few studies have addressed the immunological consequences of adipose tissue infection.
- Resource type:
- Article
- Affiliation Label Tesim:
- Department of Genetics
- DOI:
- https://doi.org/10.17615/j1b8-vy05
- Edition:
- Publisher
- Identifier:
- https://doi.org/10.3389/fimmu.2024.1360262
- ISSN:
- 1664-3224
- Journal Title:
- Frontiers in Immunology
- Journal Volume:
- 15
- Keyword:
- adaptive immunity, adipose tissue, innate immune cells, diet-induced obesity, metabolism, and infection
- Language Label:
- English
- License Label:
- Attribution 4.0 International
- Other Affiliation:
- Universidade do Porto, , and Universite Paris-Saclay
- Person:
- Teixeira, Luzia, Whitmire, Jason K., and Bourgeois, Christine
- Publisher:
- Frontiers
- Rights Statement Label:
- In Copyright
- Source:
- e031516d-22b1-4358-b622-d1696b8bbef2
23. Data sources and applied methods for paclitaxel safety signal discernment
- Title Tesim:
- Data sources and applied methods for paclitaxel safety signal discernment
- Creator:
- Avalos-Pacheco, Alejandra, Mack, Christina D., Marinac-Dabic, Danica, Ritchey, Mary E., Liebeskind, Alexander, Avila-Tang, Erika, Kinard, Madris, Torosyan, Yelizaveta, Normand, Sharon-Lise, Mao, Jialin, Shaya, Fadia T., and Gressler, Laura Elisabeth
- Date of publication:
- 2024
- Abstract Tesim:
- Background Following the identification of a late mortality signal, the Food and Drug Administration (FDA) convened an advisory panel that concluded that additional clinical study data are needed to comprehensively evaluate the late mortality signal observed with the use of drug-coated balloons (DCB) and drug-eluting stent (DES). The objective of this review is to (1) identify and summarize the existing clinical and cohort studies assessing paclitaxel-coated DCBs and DESs, (2) describe and determine the quality of the available data sources for the evaluation of these devices, and (3) present methodologies that can be leveraged for proper signal discernment within available data sources. Methods Studies and data sources were identified through comprehensive searches. original research studies, clinical trials, comparative studies, multicenter studies, and observational cohort studies written in the English language and published from January 2007 to November 2021, with a follow-up longer than 36 months, were included in the review. Data quality of available data sources identified was assessed in three groupings. Moreover, accepted data-driven methodologies that may help circumvent the limitations of the extracted studies and data sources were extracted and described. Results There were 39 studies and data sources identified. This included 19 randomized clinical trials, nine single-arm studies, eight registries, three administrative claims, and electronic health records. Methodologies focusing on the use of existing premarket clinical data, the incorporation of all contributed patient time, the use of aggregated data, approaches for individual-level data, machine learning and artificial intelligence approaches, Bayesian approaches, and the combination of various datasets were summarized. Conclusion Despite the multitude of available studies over the course of eleven years following the first clinical trial, the FDA-convened advisory panel found them insufficient for comprehensively assessing the late-mortality signal. High-quality data sources with the capabilities of employing advanced statistical methodologies are needed to detect potential safety signals in a timely manner and allow regulatory bodies to act quickly when a safety signal is detected.
- Resource type:
- Article
- Affiliation Label Tesim:
- Department of Epidemiology
- DOI:
- https://doi.org/10.17615/a733-7v22
- Edition:
- Publisher
- Identifier:
- https://doi.org/10.3389/fcvm.2023.1331142
- ISSN:
- 2297-055X
- Journal Title:
- Frontiers in Cardiovascular Medicine
- Journal Volume:
- 10
- Keyword:
- data quality, balloons, paclitaxel-coated devices, signal discernment, stents, and latemortality
- Language Label:
- English
- License Label:
- Attribution 4.0 International
- Other Affiliation:
- , United States Food and Drug Administration, Rutgers University, Device Events, and Harvard Medical School
- Person:
- Avalos-Pacheco, Alejandra, Mack, Christina D., Marinac-Dabic, Danica, Ritchey, Mary E., Liebeskind, Alexander, Avila-Tang, Erika, Kinard, Madris, Torosyan, Yelizaveta, Normand, Sharon-Lise, Mao, Jialin, Shaya, Fadia T., and Gressler, Laura Elisabeth
- Publisher:
- Frontiers
- Rights Statement Label:
- In Copyright
- Source:
- d36c5e2b-809b-48bc-af44-b48c55836a0e
24. Corpora amylacea negatively correlate with hippocampal tau pathology in Alzheimer’s disease
- Title Tesim:
- Corpora amylacea negatively correlate with hippocampal tau pathology in Alzheimer’s disease
- Creator:
- Sun, Xiaoyan, Brzostowicki, Daniel, Gober, Ryan, Vontell, Regina T., Bennett, Illiana, Garamszegi, Susanna P., Dorfsman, Daniel A., Davis, David A., Cohen, Todd, Scott, William K., Dallmeier, Julian D., Wander, Connor M., and Barreda, Ayled
- Date of publication:
- 2024
- Abstract Tesim:
- Introduction Severity and distribution of aggregated tau and neurofibrillary tangles (NFT) are strongly correlated with the clinical presentation of Alzheimer’s disease (AD). Clearance of aggregated tau could decrease the rate of NFT formation and delay AD onset. Recent studies implicate corpora amylacea (CA) as a regulator of onset or accumulation of tau pathology. Normally, CA clear brain waste products by amassing cellular debris, which are then extruded into the cerebrospinal fluid to be phagocytosed. The proper functioning of CA may slow progression of AD-associated NFT pathology, and this relationship may be influenced by amount and distribution of phospho-tau (pTau) produced, age, sex, and genetic risk. Objective The goal of this study was to determine if CA size and number are associated with hippocampal location and local pTau severity while accounting for variations in age, sex, and genetic risk. Methods Postmortem brain hippocampal tissue sections from 40 AD and 38 unaffected donors were immunohistochemically stained with AT8 (pTau) and counter stained with periodic acid Schiff (PAS). Stained sections of the CA1 and CA3 regions of the hippocampus were analyzed. The percent area occupied (%AO) of CA, pTau, and NFT was calculated. Pairwise comparisons and regression modeling were used to analyze the influence of age, pTau %AO, and genetic risk on %AO by CA in each region, separately in donors with AD and unaffected donors. Results CA %AO was significantly higher in the CA3 region compared to CA1 in both groups. A significant negative correlation of CA %AO with both pTau %AO and neurofibrillary tangle %AO in the CA3 region of AD brain donors was found. Regression analysis in the CA3 region revealed a significant negative association between CA with both pTau and age.ConclusionWe found an increase of CA in the CA3 region, compared to CA1 region, in AD and unaffected donors. This may suggest that the CA3 region is a hub for waste removal. Additionally, the negative correlation between %AO by CA and NFT in the CA3 region of the hippocampus in donors with AD suggests CA could play a role in AD pathologic progression by influencing tau clearance.
- Resource type:
- Article
- Affiliation Label Tesim:
- Department of Neurology
- DOI:
- https://doi.org/10.17615/xmkc-nm22
- Edition:
- Publisher
- Identifier:
- https://doi.org/10.3389/fnins.2024.1286924
- ISSN:
- 1662-453X
- Journal Title:
- Frontiers in Neuroscience
- Journal Volume:
- 18
- Keyword:
- wasteosomes, brain, neuropathology, Alzheimer’s disease, neurofibrillary tangles, corpora amylacea, and APOE
- Language Label:
- English
- License Label:
- Attribution 4.0 International
- Other Affiliation:
- University of Miami Miller School of Medicine and
- Person:
- Sun, Xiaoyan, Brzostowicki, Daniel, Gober, Ryan, Vontell, Regina T., Bennett, Illiana, Garamszegi, Susanna P., Dorfsman, Daniel A., Davis, David A., Cohen, Todd, Scott, William K., Dallmeier, Julian D., Wander, Connor M., and Barreda, Ayled
- Publisher:
- Frontiers
- Rights Statement Label:
- In Copyright
- Source:
- 9f1ede2d-0b76-42d9-b05f-d806f5468f8d
25. Biobehavioral survey using time location sampling among female sex workers living in Ghana in 2020
- Title Tesim:
- Biobehavioral survey using time location sampling among female sex workers living in Ghana in 2020
- Creator:
- Torpey, Kwasi, Atuahene, Kyeremeh, Ankomah, Augustine, Asamoah-Adu, Comfort, Guure, Chris, Weir, Sharon Stucker, Kenu, Ernest, Dery, Samuel, Afagbedzi, Seth, Arhinful, Daniel, Tun, Waimar, and Ampofo, William
- Date of publication:
- 2024
- Abstract Tesim:
- Background The HIV epidemic in Ghana is characterized as a mix of a low-level generalized epidemic with significant contributions from transmission among female sex workers (FSW) and their clients. This study seeks to identify and describe key characteristics and sexual behaviors of FSW and estimate the prevalence of HIV, syphilis, gonorrhea, chlamydia, and hepatitis B virus (HBV) among FSW in Ghana. Method A total of 7,000 FSW were recruited for the study using Time Location Sampling (TLS) approach with 5,990 (85.6%) participants completing both biological and the behavioral aspects of the study. A structured questionnaire was administered to respondents to assess several factors, such as background characteristics, sexual risk behaviors, condom usage, HIV/AIDS knowledge, opinions, and attitudes. Trained staff conducted face-to-face interviews using mobile data collection software (REDCap) after provision of specimens for HIV and STI testing. Descriptive statistics such as medians, ranges, charts, and percentages are performed and presented. Also included, are bivariate analyses to establish relationships between FSW type and other relevant characteristics of the study. Results Among the 7,000 (100%) FSW sampled from all regions, 6,773 took part in the behavioral and 6,217 the biological. There were 783 (11.2%) respondents who took part only in the behavioral and 227 (3.2%) only in the biological. Most were young, with a median age of 26 years, majority had never been married or were widowed/divorced and a quarter had no education or had only primary education. Majority (74.8%) of FSW first sold sex at age 25 years or less with a median age of 20 years. Most (84.8%) of the FSW indicated that they entered sex work for money, either for self or family and had an average of eleven (11) sexual partners per week. More than half (55.2%) of the FSW were new entrants who had been in sex work for less than 5 years before the study. Consistent condom use with paying clients was generally unsatisfactory (71%), and was however, very low (24%) with their intimate partners or boyfriends. Only about half (54.6%) of FSW have been exposed to HIV prevention services in the last three months preceding the survey, and this varies across regions. Overall, comprehensive knowledge about HIV and AIDS was low. Only 35% of FSW had comprehensive knowledge. HIV prevalence was 4.6% and was higher among seaters (brothel-based) and older FSW who had been sex work for a longer period. The HIV prevalence from the previous bio-behavioral survey (BBS) in 2015 and 2011 were estimated to be 6.9 and 11.1%, respectively. Conclusion Compared to the results from the previous studies, the findings give an indication that Ghana is making significant progress in reducing the burden of HIV among FSW in the country. However, risky behaviors such as low consistent condom use, low coverage of HIV services across the regions, and low comprehensive knowledge could reverse the gains made so far. Immediate actions should be taken to expand coverage of HIV services to all locations. Efforts must be made to reach out to the new entrants while also addressing strongly held myths and misconceptions about HIV.
- Resource type:
- Article
- Affiliation Label Tesim:
- Department of Epidemiology
- DOI:
- https://doi.org/10.17615/akj8-m482
- Edition:
- Publisher
- Identifier:
- https://doi.org/10.3389/fpubh.2024.1137799
- ISSN:
- 2296-2565
- Journal Title:
- Frontiers in Public Health
- Journal Volume:
- 12
- Keyword:
- venue-day time sampling, female sex workers, commercial sex workers, time location sampling, STIs, HIV, roamer population, and seater population
- Language Label:
- English
- License Label:
- Attribution 4.0 International
- Other Affiliation:
- University of Ghana, Ghana AIDS Commission,, Population Council, Accra, West Africa Program to Combat AIDS and STI, , University of Ghana Noguchi Memorial Institute for Medical Research, and Population Council, Washington, DC
- Person:
- Torpey, Kwasi, Atuahene, Kyeremeh, Ankomah, Augustine, Asamoah-Adu, Comfort, Guure, Chris, Weir, Sharon Stucker, Kenu, Ernest, Dery, Samuel, Afagbedzi, Seth, Arhinful, Daniel, Tun, Waimar, and Ampofo, William
- Publisher:
- Frontiers
- Rights Statement Label:
- In Copyright
- Source:
- ccd88b52-235a-4c37-86c1-3a5084616d8e
26. Behind the screen: drug discovery using the big data of phenotypic analysis
- Title Tesim:
- Behind the screen: drug discovery using the big data of phenotypic analysis
- Creator:
- Solem, Amanda C., Thomas, Aeisha, Pattenden, Samantha G., Froney, Merrill M., Jarstfer, Michael B., Aina, Olubunmi O., Alexander, Courtney M., and Eslinger, Melissa R.
- Date of publication:
- 2024
- Abstract Tesim:
- Technological advances in drug discovery are exciting to students, but it is challenging for faculty to maintain the pace with these developments, particularly within undergraduate courses. In recent years, a High-throughput Discovery Science and Inquiry-based Case Studies for Today’s Students (HITS) Research Coordination Network has been assembled to address the mechanism of how faculty can, on-pace, introduce these advancements. As a part of HITS, our team has developed “Behind the Screen: Drug Discovery using the Big Data of Phenotypic Analysis” to introduce students and faculty to phenotypic screening as a tool to identify inhibitors of diseases that do not have known cellular targets. This case guides faculty and students though current screening methods using statistics and can be applied at undergraduate and graduate levels. Tested across 70 students at three universities and a variety of courses, our case utilizes datasets modeled on a real phenotypic screening method as an accessible way to teach students about current methods in drug discovery. Students will learn how to identify hit compounds from a dataset they have analyzed and understand the biological significance of the results they generate. They are guided through practical statistical procedures, like those of researchers engaging in a novel drug discovery strategy. Student survey data demonstrated that the case was successful in improving student attitudes in their ability to discuss key topics, with both undergraduate and graduate students having a significant increase in confidence. Together, we present a case that uses big data to examine the utility of a novel phenotypic screening strategy, a pedagogical tool that can be customized for a wide variety of courses.
- Resource type:
- Article
- Affiliation Label Tesim:
- Division of Chemical Biology and Medicinal Chemistry
- DOI:
- https://doi.org/10.17615/vbba-ry37
- Edition:
- Publisher
- Identifier:
- https://doi.org/10.3389/feduc.2024.1342378
- ISSN:
- 2504-284X
- Journal Title:
- Frontiers in Education
- Journal Volume:
- 9
- Keyword:
- drug discovery, active learning, case study, big data, education, and high throughput screening
- Language Label:
- English
- License Label:
- Attribution 4.0 International
- Other Affiliation:
- Hastings College, Crown College, , Allen University, University of North Carolina at Pembroke, and United States Military Academy
- Person:
- Solem, Amanda C., Thomas, Aeisha, Pattenden, Samantha G., Froney, Merrill M., Jarstfer, Michael B., Aina, Olubunmi O., Alexander, Courtney M., and Eslinger, Melissa R.
- Publisher:
- Frontiers
- Rights Statement Label:
- In Copyright
- Source:
- 5ba59ea8-7537-46f3-9b4d-f0ffc946a496
27. Communication, theory of change, and clean energy
- Title Tesim:
- Communication, theory of change, and clean energy
- Creator:
- Cox, Robert
- Date of publication:
- 2024
- Abstract Tesim:
- Some years ago, I stepped away from my faculty position at the University of North Carolina at Chapel Hill (UNC) to become more deeply engaged with the Sierra Club, one of the oldest environmental NGOs in the United States. Given my research, I knew insights into strategic communication in advocacy campaigns would likely be applicable, particularly, to the climate change efforts in which I was planning to participate. Climate change campaigns, like campaigns focused on other issues, usually involve multiple forms of communication—grassroots organizing, social media, demonstrations, media coverage, placards, canvassing, etc. Beyond these tactical uses, NGOs also may conceive a strategic rationale for a campaign itself as derived from core communication principles. As it turned out, I would have an opportunity to help to design one such campaign, a message driven initiative to accelerate the movement toward a greater commitment to use 100% clean, renewable energy in the United States.
- Resource type:
- Article
- Affiliation Label Tesim:
- University of North Carolina at Chapel Hill
- DOI:
- https://doi.org/10.17615/815z-n053
- Edition:
- Publisher
- Identifier:
- https://doi.org/10.3389/fcomm.2024.1381928
- ISSN:
- 2297-900X
- Journal Title:
- Frontiers in Communication
- Journal Volume:
- 9
- Keyword:
- campaign, strategy, theory of change, climate change communication, and clean energy
- Language Label:
- English
- License Label:
- Attribution 4.0 International
- Other Affiliation:
- Person:
- Cox, Robert
- Publisher:
- Frontiers
- Rights Statement Label:
- In Copyright
- Source:
- 79e1eee8-1209-4767-b1e7-c69ab90c0035
28. Findings from the Hispanic Community Health Study/Study of Latinos on the Importance of Sociocultural Environmental Interactors: Polygenic Risk Score-by-Immigration and Dietary Interactions
- Title Tesim:
- Findings from the Hispanic Community Health Study/Study of Latinos on the Importance of Sociocultural Environmental Interactors: Polygenic Risk Score-by-Immigration and Dietary Interactions
- Creator:
- Preudhomme, L.K., Rodell, C.C., Pirzada, A., Cai, J., Daviglus, M.L., Graff, M., Fernandez-Rhodes, L., McArdle, C.E., Bokhari, H., Gallo, L.C., Isasi, C.R., Wojcik, G., North, K., Buchanan, V., and Perreira, K.
- Date of publication:
- 2021
- Abstract Tesim:
- Introduction: Hispanic/Latinos experience a disproportionate burden of obesity. Acculturation to US obesogenic diet and practices may lead to an exacerbation of innate genetic susceptibility. We examined the role of gene–environment interactions to better characterize the sociocultural environmental determinants and their genome-scale interactions, which may contribute to missing heritability of obesity. We utilized polygenic risk scores (PRSs) for body mass index (BMI) to perform analyses of PRS-by-acculturation and other environmental interactors among self-identified Hispanic/Latino adults from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Methods: PRSs were derived using genome-wide association study (GWAS) weights from a publicly available, large meta-analysis of European ancestry samples. Generalized linear models were run using a set of a priori acculturation-related and environmental factors measured at visit 1 (2008–2011) and visit 2 (2014–2016) in an analytic subsample of 8,109 unrelated individuals with genotypic, phenotypic, and complete case data at both visits. We evaluated continuous measures of BMI and waist-to-hip ratio. All models were weighted for complex sampling design, combined, and sex-stratified. Results: Overall, we observed a consistent increase of BMI with greater PRS across both visits. We found the best-fitting model adjusted for top five principal components of ancestry, sex, age, study site, Hispanic/Latino background genetic ancestry group, sociocultural factors and PRS interactions with age at immigration, years since first arrival to the United States (p < 0.0104), and healthy diet (p < 0.0036) and explained 16% of the variation in BMI. For every 1-SD increase in PRS, there was a corresponding 1.10 kg/m2 increase in BMI (p < 0.001). When these results were stratified by sex, we observed that this 1-SD effect of PRS on BMI was greater for women than men (1.45 vs. 0.79 kg/m2, p < 0.001). Discussion: We observe that age at immigration and the adoption of certain dietary patterns may play a significant role in modifying the effect of genetic risk on obesity. Careful consideration of sociocultural and immigration-related factors should be evaluated. The role of nongenetic factors, including the social environment, should not be overlooked when describing the performance of PRS or for promoting population health in understudied populations in genomics.
- Resource type:
- Article
- Affiliation Label Tesim:
- Department of Biostatistics, Department of Epidemiology, and Department of Social Medicine
- DOI:
- https://doi.org/10.17615/w2hj-pp31
- Edition:
- Publisher
- Identifier:
- https://doi.org/10.3389/fgene.2021.720750
- ISSN:
- 1664-8021
- Journal Title:
- Frontiers in Genetics
- Journal Volume:
- 12
- Keyword:
- Hispanic/Latino, polygenic risk score, gene-environment interactions, obesity, and acculturation
- Language Label:
- English
- License Label:
- Attribution 4.0 International
- ORCID:
- Other Affiliation:
- University of Miami, Johns Hopkins University, University of Illinois at Urbana–Champaign, , University of Illinois at Chicago, The Pennsylvania State University, San Diego State University, and Albert Einstein College of Medicine
- Person:
- Preudhomme, L.K., Rodell, C.C., Pirzada, A., Cai, J., Daviglus, M.L., Graff, M., Fernandez-Rhodes, L., McArdle, C.E., Bokhari, H., Gallo, L.C., Isasi, C.R., Wojcik, G., North, K., Buchanan, V., and Perreira, K.
- Publisher:
- Frontiers Media S.A.
- Source:
- 9b3c375c-b2b9-4509-8426-670b34451146
29. Genetic variants related to cardiometabolic traits are associated to B cell function, insulin resistance, and diabetes among American Indians: The strong heart family study
- Title Tesim:
- Genetic variants related to cardiometabolic traits are associated to B cell function, insulin resistance, and diabetes among American Indians: The strong heart family study
- Creator:
- Balakrishnan, P., Haack, K., Best, L.G., Voruganti, V.S., Franceschini, N., Navas-Acien, A., Kent, J.W., Umans, J.G., Lee, E.T., Howard, B.V., Cole, S.A., Laston, S., MacCluer, J.W., North, K.E., and Vaidya, D.
- Date of publication:
- 2018
- Abstract Tesim:
- Background: Genetic research may inform underlying mechanisms for disparities in the burden of type 2 diabetes mellitus among American Indians. Our objective was to assess the association of genetic variants in cardiometabolic candidate genes with B cell dysfunction via HOMA-B, insulin resistance via HOMA-IR, and type 2 diabetes mellitus in the Strong Heart Family Study (SHFS). Methods and Results: We examined the association of variants, previously associated with cardiometabolic traits (∼200,000 from Illumina Cardio MetaboChip), using mixed models of HOMA-B residuals corrected for HOMA-IR (cHOMA-B), log transformed HOMAIR, and incident diabetes, adjusted for age, sex, population stratification, and familial relatedness. Center-specific estimates were combined using fixed effect meta-analyses. We used Bonferroni correction to account for multiple testing (P < 4.13 × 10-7). We also assessed the association between variants in candidate diabetes genes with these metabolic traits. We explored the top SNPs in an independent, replication sample from Southwestern Arizona. We identified significant associations with cHOMA-B for common variants at 26 loci of which 8 were novel (PRSS7, FCRL5, PEL1, LRP12, IGLL1, ARHGEF10, PARVA, FLJ16686). The most significant variant association with cHOMA-B was observed on chromosome 5 for an intergenic variant near PARP8 (rs2961831, P = 6.39 × 10-9). In the replication study, we found a signal at rs4607517 near GCK/YKT6 (P = 0.01). Variants near candidate diabetes genes (especially GCK and KCNQ1) were also nominally associated with HOMA-IR and cHOMA-B. Conclusion: We identified variants at novel loci and confirmed those at known candidate diabetes loci associations for cHOMA-B. This study also provided evidence for association of variants at KCNQ2, CTNAA2, and KCNQ1 with cHOMA-B among American Indians. Further studies are needed to account for the high heritability of diabetes among the American Indian participants of the SHFS cohort.
- Resource type:
- Article
- Affiliation Label Tesim:
- Department of Nutrition and Department of Epidemiology
- DOI:
- https://doi.org/10.17615/zg5f-xg48
- Edition:
- Publisher
- Identifier:
- https://dx.doi.org/10.3389/fgene.2018.00466
- Journal Issue:
- OCT
- Journal Title:
- Frontiers in Genetics
- Journal Volume:
- 9
- Keyword:
- Insulin resistance, Diabetes mellitus, Genome-wide association study, Insulin-secreting cells, and American Indian
- Language Label:
- English
- License Label:
- Attribution 4.0 International
- Other Affiliation:
- Columbia University Mailman School of Public Health, Texas Biomedical Research Institute, Missouri Breaks Industries Research, Inc., , MedStar Health Research Institute, University of Oklahoma Health Sciences Center, University of Texas, Rio Grande Valley, and Johns Hopkins University
- Person:
- Balakrishnan, P., Haack, K., Best, L.G., Voruganti, V.S., Franceschini, N., Navas-Acien, A., Kent, J.W., Umans, J.G., Lee, E.T., Howard, B.V., Cole, S.A., Laston, S., MacCluer, J.W., North, K.E., and Vaidya, D.
- Rights Statement Label:
- In Copyright
- Source:
- 2268f421-3321-4aab-8b7d-197e4e7a8595
30. Multi-omics insights into the biological mechanisms underlying statistical gene-by-lifestyle interactions with smoking and alcohol consumption
- Title Tesim:
- Multi-omics insights into the biological mechanisms underlying statistical gene-by-lifestyle interactions with smoking and alcohol consumption
- Creator:
- CHARGE Gene-Lifestyle Interactions Working Group, Schwander, K., Majarian, T.D., Rotimi, C.N., Rao, D.C., Chasman, D.I., Manning, A.K., Bentley, A.R., Levy, D., Province, M., Franceschini, N., Sung, Y.J., Laville, V., Feitosa, M.F., Gauderman, W.J., de Vries, P.S., Aschard, H., Brown, M.R., Marchek, C., Morrison, A.C., and Gu, C.C.
- Date of publication:
- 2022
- Abstract Tesim:
- Though both genetic and lifestyle factors are known to influence cardiometabolic outcomes, less attention has been given to whether lifestyle exposures can alter the association between a genetic variant and these outcomes. The Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium’s Gene-Lifestyle Interactions Working Group has recently published investigations of genome-wide gene-environment interactions in large multi-ancestry meta-analyses with a focus on cigarette smoking and alcohol consumption as lifestyle factors and blood pressure and serum lipids as outcomes. Further description of the biological mechanisms underlying these statistical interactions would represent a significant advance in our understanding of gene-environment interactions, yet accessing and harmonizing individual-level genetic and ‘omics data is challenging. Here, we demonstrate the coordinated use of summary-level data for gene-lifestyle interaction associations on up to 600,000 individuals, differential methylation data, and gene expression data for the characterization and prioritization of loci for future follow-up analyses. Using this approach, we identify 48 genes for which there are multiple sources of functional support for the identified gene-lifestyle interaction. We also identified five genes for which differential expression was observed by the same lifestyle factor for which a gene-lifestyle interaction was found. For instance, in gene-lifestyle interaction analysis, the T allele of rs6490056 (ALDH2) was associated with higher systolic blood pressure, and a larger effect was observed in smokers compared to non-smokers. In gene expression studies, this allele is associated with decreased expression of ALDH2, which is part of a major oxidative pathway. Other results show increased expression of ALDH2 among smokers. Oxidative stress is known to contribute to worsening blood pressure. Together these data support the hypothesis that rs6490056 reduces expression of ALDH2, which raises oxidative stress, leading to an increase in blood pressure, with a stronger effect among smokers, in whom the burden of oxidative stress is greater. Other genes for which the aggregation of data types suggest a potential mechanism include: GCNT4×current smoking (HDL), PTPRZ1×ever-smoking (HDL), SYN2×current smoking (pulse pressure), and TMEM116×ever-smoking (mean arterial pressure). This work demonstrates the utility of careful curation of summary-level data from a variety of sources to prioritize gene-lifestyle interaction loci for follow-up analyses.
- Resource type:
- Article
- Affiliation Label Tesim:
- Department of Epidemiology
- DOI:
- https://doi.org/10.17615/t3q1-6510
- Edition:
- Publisher
- Identifier:
- https://dx.doi.org/10.3389/fgene.2022.954713
- ISSN:
- 1664-8021
- Journal Title:
- Frontiers in Genetics
- Journal Volume:
- 13
- Keyword:
- blood pressure, smoking, gene-lifestyle interactions, summary data, multi-omics, alcohol, and serum lipids
- Language Label:
- English
- License Label:
- Attribution 4.0 International
- Other Affiliation:
- , Washington University School of Medicine, Broad Institute of MIT and Harvard, National Institutes of Health,, Harvard Medical School, Massachusetts General Hospital, National Institutes of Health, NIH, Université Paris Cité, University of Southern California, University of Texas Health Science Center at Houston, Harvard T.H. Chan School of Public Health, and The University of Texas Health Science Center at Houston
- Person:
- CHARGE Gene-Lifestyle Interactions Working Group, Schwander, K., Majarian, T.D., Rotimi, C.N., Rao, D.C., Chasman, D.I., Manning, A.K., Bentley, A.R., Levy, D., Province, M., Franceschini, N., Sung, Y.J., Laville, V., Feitosa, M.F., Gauderman, W.J., de Vries, P.S., Aschard, H., Brown, M.R., Marchek, C., Morrison, A.C., and Gu, C.C.
- Publisher:
- Frontiers Media S.A.
- Rights Statement Label:
- In Copyright
- Source:
- b6f5a542-716f-41f4-8fa6-dc834eee61f6
Collection Details
- Total items
-
762
- Size
-
unknown
- Date created
-
May 26, 2022