15 research outputs found
THE ASSOCIATION OF SINGLE NUCLEOTIDE POLYMORPHISMS IN INTRONIC REGIONS OF ISLET CELL AUTOANTIGEN 1 AND TYPE 1 DIABETES MELLITUS
Type 1 diabetes mellitus is a multifactorial autoimmune disease caused by a combination of genetic and environmental factors. Further knowledge and understanding about the genes which play a role in type 1 diabetes has a clear public health significance in that it will aid in the prediction, treatment and a possible cure. Type 1 diabetes is a chronic disease with a lengthy preclinical course, which eventually results in pancreatic beta cell destruction and inability of the body to produce insulin hormone. Type 1 diabetic patients generally require exogenous insulin to survive. Several genetic loci have been proposed to be linked to type 1 diabetes; however, the HLA and VNTR regions are currently believed to account for the majority of genetic risk, contributing to about 42% and 10% of an individual's risk to develop type 1 diabetes, respectively. This study focuses on the candidate gene Islet Cell Autoantigen 1 (ICA1), which codes for the protein ICA69. This protein product is expressed in the islets of Langerhans, the neuroendocrine system and in the thymic medulla; this last location is an area of the body known to play a major role in immunologic tolerance. Preliminary studies in the NOD and B6 mouse models suggest that a SNP within the promoter region of Ica1 affects transcription and may account for altered expression in the thymus. Our current study aimed to determine whether single nucleotide polymorphisms within intronic regions of the human ICA1 gene differed between a diabetic case population and non-diabetic controls. It was hypothesized that SNPs within the ICA1 gene differ between cases and controls and play a role in the onset of type 1 diabetes. Polymerase Chain Reaction (PCR) was applied for DNA amplification and the pyrosequencing technique was used to genotype all samples. At SNP location rs2058519 there was a clear genotypic difference between the cases and controls (p= .0003). These results suggest that genetic variation at this specific SNP location in the ICA1 may be associated with type 1 diabetes susceptibility. The ultimate goal of this study is to determine whether our candidate gene ICA1 appears to play a role in the pathogenesis of type 1 diabetes
Understanding the Return of Genomic Sequencing Results Process: Content Review of Participant Summary Letters in the eMERGE Research Network
A challenge in returning genomic test results to research participants is how best to communicate complex and clinically nuanced findings to participants in a manner that is scalable to the large numbers of participants enrolled. The purpose of this study was to examine the features of genetic results letters produced at each Electronic Medical Records and Genomics (eMERGE3) Network site to assess their readability and content. Letters were collected from each site, and a qualitative analysis of letter content and a quantitative analysis of readability statistics were performed. Because letters were produced independently at each eMERGE site, significant heterogeneity in readability and content was found. The content of letters varied widely from a baseline of notifying participants that results existed to more detailed information about positive or negative results, as well as materials for sharing with family members. Most letters were significantly above the Centers for Disease Control-suggested reading level for health communication. While continued effort should be applied to make letters easier to understand, the ongoing challenge of explaining complex genomic information, the implications of negative test results, and the uncertainty that comes with some types of test and result makes simplifying letter text challenging
Clinical Sequencing Exploratory Research Consortium: Accelerating Evidence-Based Practice of Genomic Medicine
Despite rapid technical progress and demonstrable effectiveness for some types of diagnosis and therapy, much remains to be learned about clinical genome and exome sequencing (CGES) and its role within the practice of medicine. The Clinical Sequencing Exploratory Research (CSER) consortium includes 18 extramural research projects, one National Human Genome Research Institute (NHGRI) intramural project, and a coordinating center funded by the NHGRI and National Cancer Institute. The consortium is exploring analytic and clinical validity and utility, as well as the ethical, legal, and social implications of sequencing via multidisciplinary approaches; it has thus far recruited 5,577 participants across a spectrum of symptomatic and healthy children and adults by utilizing both germline and cancer sequencing. The CSER consortium is analyzing data and creating publically available procedures and tools related to participant preferences and consent, variant classification, disclosure and management of primary and secondary findings, health outcomes, and integration with electronic health records. Future research directions will refine measures of clinical utility of CGES in both germline and somatic testing, evaluate the use of CGES for screening in healthy individuals, explore the penetrance of pathogenic variants through extensive phenotyping, reduce discordances in public databases of genes and variants, examine social and ethnic disparities in the provision of genomics services, explore regulatory issues, and estimate the value and downstream costs of sequencing. The CSER consortium has established a shared community of research sites by using diverse approaches to pursue the evidence-based development of best practices in genomic medicine
Workforce Considerations When Building a Precision Medicine Program
This paper describes one healthcare system’s approach to strategically deploying genetic specialists and pharmacists to support the implementation of a precision medicine program. In 2013, Sanford Health initiated the development of a healthcare system-wide precision medicine program. Here, we report the necessary staffing including the genetic counselors, genetic counseling assistants, pharmacists, and geneticists. We examined the administrative and electronic medical records data to summarize genetic referrals over time as well as the uptake and results of an enterprise-wide genetic screening test. Between 2013 and 2020, the number of genetic specialists employed at Sanford Health increased by 190%, from 10.1 full-time equivalents (FTEs) to 29.3 FTEs. Over the same period, referrals from multiple provider types to genetic services increased by 423%, from 1438 referrals to 7517 referrals. Between 2018 and 2020, 11,771 patients received a genetic screening, with 4% identified with potential monogenic medically actionable predisposition (MAP) findings and 95% identified with at least one informative pharmacogenetic result. Of the MAP-positive patients, 85% had completed a session with a genetics provider. A strategic workforce staffing and deployment allowed Sanford Health to manage a new genetic screening program, which prompted a large increase in genetic referrals. This approach can be used as a template for other healthcare systems interested in the development of a precision medicine program
Attitudes about pharmacogenomic testing vary by healthcare specialty
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Short-term costs of integrating whole-genome sequencing into primary care and cardiology settings: a pilot randomized trial.
PurposeGreat uncertainty exists about the costs associated with whole-genome sequencing (WGS).MethodsOne hundred cardiology patients with cardiomyopathy diagnoses and 100 ostensibly healthy primary care patients were randomized to receive a family-history report alone or with a WGS report. Cardiology patients also reviewed prior genetic test results. WGS costs were estimated by tracking resource use and staff time. Downstream costs were estimated by identifying services in administrative data, medical records, and patient surveys for 6 months.ResultsThe incremental cost per patient of WGS testing was 5,073 in primary care settings compared with family history alone. Mean 6-month downstream costs did not differ statistically between the control and WGS arms in either setting (cardiology: difference = -7,558 to 681, 95% confidence interval -2,171, p = 0.70). Scenario analyses showed the cost reduction of omitting or limiting the types of secondary findings was less than 182 per patient in cardiology and primary care, respectively.ConclusionShort-term costs of WGS were driven by the costs of sequencing and interpretation rather than downstream health care. Disclosing additional types of secondary findings has a limited cost impact following disclosure
Awareness and utilization of genetic testing among Hispanic and Latino adults living in the US: The Hispanic Health of Latinos
We investigated the awareness, perceived usefulness, and use of genetic testing among Hispanic and Latino individuals. Annual followup surveys for the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) from 2019 to April 2020 assessed participants' level of awareness and use of genetic tests to determine disease risks, likelihood of passing disease to children, disease treatment, or drug selection. They also were asked to rate the usefulness of the tests for managing a person's health on a 1 (not at all useful) to 10 (extremely useful) scale. There were 5,769 HCHS/SOL participants who completed at least one survey question. Of the target population, 55.2% was aware of at least one type of genetic test. Awareness varied between HCHS/SOL enrollment sites and was higher among individuals who had higher educational attainment and had higher incomes. Only 3.3% of the target population reported receiving one or more of the tests described. HCHS/SOL individuals rated the usefulness as 8.4, on average, with lower scores observed among U.S.-born individuals compared to individuals born outside the United States, with differences by HCHS/SOL enrollment sites. In conclusion, while awareness of genetic testing among Hispanic and Latino individuals varies by location, education, and income, perceptions about its usefulness are high while experiences with testing are rare. Results identify groups and locations that may benefit from greater outreach about the capabilities of genetic testing and precision medicine
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Short-term costs of integrating whole-genome sequencing into primary care and cardiology settings: a pilot randomized trial.
PurposeGreat uncertainty exists about the costs associated with whole-genome sequencing (WGS).MethodsOne hundred cardiology patients with cardiomyopathy diagnoses and 100 ostensibly healthy primary care patients were randomized to receive a family-history report alone or with a WGS report. Cardiology patients also reviewed prior genetic test results. WGS costs were estimated by tracking resource use and staff time. Downstream costs were estimated by identifying services in administrative data, medical records, and patient surveys for 6 months.ResultsThe incremental cost per patient of WGS testing was 5,073 in primary care settings compared with family history alone. Mean 6-month downstream costs did not differ statistically between the control and WGS arms in either setting (cardiology: difference = -7,558 to 681, 95% confidence interval -2,171, p = 0.70). Scenario analyses showed the cost reduction of omitting or limiting the types of secondary findings was less than 182 per patient in cardiology and primary care, respectively.ConclusionShort-term costs of WGS were driven by the costs of sequencing and interpretation rather than downstream health care. Disclosing additional types of secondary findings has a limited cost impact following disclosure
Additional file 1 of Patient and provider perspectives on polygenic risk scores: implications for clinical reporting and utilization
Additional file 1: Tables S1 and S2. Further information on patient survey items; Patient interview guide, with mock report designs; Primary Care Physician interview guide, with mock report designs