Association of genetically-predicted placental gene expression with adult blood pressure traits.

Objective: Blood pressure is a complex, polygenic trait, and the need to identify prehypertensive risks and new gene targets for blood pressure control therapies or prevention continues. We hypothesize a developmental origins model of blood pressure traits through the life course where the placenta is a conduit mediating genomic and nongenomic transmission of disease risk. Genetic control of placental gene expression has recently been described through expression quantitative trait loci (eQTL) studies which have identified associations with childhood phenotypes.

Assessing patient-level knowledge of precision medicine in a community health center setting.

As precision medicine approaches are implemented, cancer treatment decisions have come to require comprehension of genetic tests and their role in risk stratification and treatment options. Acceptance and implementation of precision medicine requires patient understanding of numeracy, genetic literacy, health literacy, and medical trust. Implementing precision medicine in a US federally qualified community health center (FQCHC) setting has received little attention.

Development and Validation of the Perceptions of Research Trustworthiness Scale to Measure Trust Among Minoritized Racial and Ethnic Groups in Biomedical Research in the US.

Importance: Historically, trust in biomedical research has been lower among minoritized racial and ethnic groups who are underrepresented in and excluded from research, with the same groups experiencing worse health outcomes. Unfortunately, instruments that measure trust may not capture components of trust relevant to minoritized racial and ethnic groups.

Objective: To develop and validate a scale to measure trust in biomedical research among minoritized racial and ethnic groups.

Development and pilot implementation of guidelines for culturally tailored research recruitment materials for African Americans and Latinos.

Background: Previous studies support cultural tailoring of recruitment materials as a strategy to promote the enrollment of minoritized groups in clinical trials. However, there is a lack of guidance for research teams to create culturally tailored materials, potentially contributing to low recruitment rates of minoritized groups. We describe the development and pilot testing of recruitment material guidelines used to culturally tailor clinical trial recruitment materials targeting African Americans and Latinos.

Design and implementation of a massive open online course on enhancing the recruitment of minorities in clinical trials - Faster Together.

Background: Racial and ethnic minorities are often underrepresented in clinical trials, threatening the generalizability of trial results. Several factors may contribute to underrepresentation of minorities in clinical trials, including lack of training for researchers and staff on the importance of diversity in clinical trials and effective strategies for recruiting and retaining minority populations.

Methods: Applying community engaged research principles, we developed a massive open online course (MOOC) to help research team members develop knowledge and skills to enhance the recruitment of minorities in clinical trials.

Determinants of stage at diagnosis of HPV-related cancer including area deprivation and clinical factors.

Background: Collecting social determinants of health in electronic health records is time-consuming. Meanwhile, an Area Deprivation Index (ADI) aggregates sociodemographic information from census data. The objective of this study was to ascertain whether ADI is associated with stage of human papillomavirus (HPV)-related cancer at diagnosis.

Patient Stories Can Make a Difference in Patient-Centered Research Design.

Amid increasing interest in improving the patient-centeredness of research, new forms of engagement are emerging that enable researchers to get input from community members on research goals, methods, and implementation. This input often includes stories, which are useful for understanding lived experiences of illness and encounters with health care organizations, and for locating these experiences within larger meta-narratives of specific communities. We analyzed the stories in transcripts of 13 Community Engagement Studios and identified 4 major functions that the stories served in the sessions.

Factors influencing precision medicine knowledge and attitudes.

Precision medicine holds great promise for improving health and reducing health disparities that can be most fully realized by advancing diversity and inclusion in research participants. Without engaging underrepresented groups, precision medicine could not only fail to achieve its promise but also further exacerbate the health disparities already burdening the most vulnerable. Yet underrepresentation by people of non-European ancestry continues in precision medicine research and there are disparities across racial groups in the uptake of precision medicine applications and services.

Determinants of Trustworthiness to Conduct Medical Research: Findings from Focus Groups Conducted with Racially and Ethnically Diverse Adults.

Background: Potential research participants, particularly those from racial and ethnic groups underrepresented in medical research, often decide to participate based on how they judge people, places, and study protocols as trustworthy. And yet, few studies have explored notions of trustworthiness or determinants of trustworthiness from the perspective of potential medical research participants.

Objective: This paper describes how racially and ethnically diverse potential medical research participants conceptualize what makes researchers, research settings, and research protocols seem trustworthy.

A taxonomy of impacts on clinical and translational research from community stakeholder engagement.

Background: Community engagement is increasingly recognized as a valuable tool in clinical and translational research; however, the impact of engagement is not fully understood. No standard nomenclature yet exists to clearly define how research changes when community stakeholders are engaged across the research spectrum. This severely limits our ability to assess the value of community engagement in research.

Heritability and genome-wide association study of benign prostatic hyperplasia (BPH) in the eMERGE network.

Benign prostatic hyperplasia (BPH) results in a significant public health burden due to the morbidity caused by the disease and many of the available remedies. As much as 70% of men over 70 will develop BPH. Few studies have been conducted to discover the genetic determinants of BPH risk.

Enrichment sampling for a multi-site patient survey using electronic health records and census data.

Objective: We describe a stratified sampling design that combines electronic health records (EHRs) and United States Census (USC) data to construct the sampling frame and an algorithm to enrich the sample with individuals belonging to rarer strata.

Materials And Methods: This design was developed for a multi-site survey that sought to examine patient concerns about and barriers to participating in research studies, especially among under-studied populations (eg, minorities, low educational attainment). We defined sampling strata by cross-tabulating several socio-demographic variables obtained from EHR and augmented with census-block-level USC data.

Development and validation of the Person-Centeredness of Research Scale.

Aim: Person-centeredness shifts the focus of healthcare and research to the needs and priorities of patients and communities, and may improve health outcomes. There are no instruments available, however, with which we can assess the degree to which research is indeed person-centered. Our aim was to develop and validate a quantitative instrument to rate person-centeredness of research.

A Multilevel Approach to Stakeholder Engagement in the Formulation of a Clinical Data Research Network.

Objectives: To ensure meaningful engagement of stakeholders (patients, clinicians, and communities) in developing the Mid-South Clinical Data Research Network (MS-CDRN), we implemented a comprehensive, multilevel approach: (1) identify barriers to involving stakeholders in governance, network design, and implementation; (2) engage stakeholders in priority setting and research topic generation; (3) develop strategies to fully integrate stakeholders in CDRN governance and oversight; and (4) solicit guidance on patient-centered tools and strategies for recruiting research participants.

Methods: We engaged stakeholders: (1) as integral research team members; (2) on oversight and advisory committees; (3) as consultants (using Community Engagement Studios); and (4) through interviews and surveys. We recruited stakeholders from community health centers, churches, barbershops, health fairs, a volunteer registry, and a patient portal.

Healthcare provider education to support integration of pharmacogenomics in practice: the eMERGE Network experience.

Ten organizations within the Electronic Medical Records and Genomics Network developed programs to implement pharmacogenomic sequencing and clinical decision support into clinical settings. Recognizing the importance of informed prescribers, a variety of strategies were used to incorporate provider education to support implementation. Education experiences with pharmacogenomics are described within the context of each organization's prior involvement, including the scope and scale of implementation specific to their Electronic Medical Records and Genomics projects.

Concordance between Research Sequencing and Clinical Pharmacogenetic Genotyping in the eMERGE-PGx Study.

There has been extensive debate about both the necessity of orthogonal confirmation of next-generation sequencing (NGS) results in Clinical Laboratory Improvement Amendments-approved laboratories and return of research NGS results to participants enrolled in research studies. In eMERGE-PGx, subjects underwent research NGS using PGRNseq and orthogonal targeted genotyping in clinical laboratories, which prompted a comparison of genotyping results between platforms. Concordance (percentage agreement) was reported for 4077 samples tested across nine combinations of research and clinical laboratories.

Conducting a large, multi-site survey about patients' views on broad consent: challenges and solutions.

Background: As biobanks play an increasing role in the genomic research that will lead to precision medicine, input from diverse and large populations of patients in a variety of health care settings will be important in order to successfully carry out such studies. One important topic is participants' views towards consent and data sharing, especially since the 2011 Advanced Notice of Proposed Rulemaking (ANPRM), and subsequently the 2015 Notice of Proposed Rulemaking (NPRM) were issued by the Department of Health and Human Services (HHS) and Office of Science and Technology Policy (OSTP). These notices required that participants consent to research uses of their de-identified tissue samples and most clinical data, and allowing such consent be obtained in a one-time, open-ended or "broad" fashion.

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.

Genetic variation among 82 pharmacogenes: The PGRNseq data from the eMERGE network.

Genetic variation can affect drug response in multiple ways, although it remains unclear how rare genetic variants affect drug response. The electronic Medical Records and Genomics (eMERGE) Network, collaborating with the Pharmacogenomics Research Network, began eMERGE-PGx, a targeted sequencing study to assess genetic variation in 82 pharmacogenes critical for implementation of "precision medicine." The February 2015 eMERGE-PGx data release includes sequence-derived data from ∼5,000 clinical subjects.

Association of Arrhythmia-Related Genetic Variants With Phenotypes Documented in Electronic Medical Records.

Importance: Large-scale DNA sequencing identifies incidental rare variants in established Mendelian disease genes, but the frequency of related clinical phenotypes in unselected patient populations is not well established. Phenotype data from electronic medical records (EMRs) may provide a resource to assess the clinical relevance of rare variants.

Objective: To determine the clinical phenotypes from EMRs for individuals with variants designated as pathogenic by expert review in arrhythmia susceptibility genes.

Penetrance of Hemochromatosis in HFE Genotypes Resulting in p.Cys282Tyr and p.[Cys282Tyr];[His63Asp] in the eMERGE Network.

Hereditary hemochromatosis (HH) is a common autosomal-recessive disorder associated with pathogenic HFE variants, most commonly those resulting in p.Cys282Tyr and p.His63Asp.

The Exploitation of Drug Users.

Drug users have been exploited in research studies and clinical practice. We explore ways in which exploitation has occurred and strategies to help patients, research subjects and communities to prevent or avoid exploitation.

Double-C loop platform in combination with hydrophobic and hydrophilic acrylic intraocular lens materials.

Purpose: To analyze the behavior of a new double-C-loop quadripod symmetrical intraocular lens (IOL) platform combined with a hydrophilic lens material and a new hydrophobic glistening-free acrylic lens material, Ankoris and Podeye, respectively, in silico (computer simulation), in vitro (laboratory investigation), and in vivo (rabbit model).

Setting: John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, USA, and Physiol S.