Return of results in the genomic medicine projects of the eMERGE network

Kullo, Iftikhar J.; Haddad, Raad A.; Prows, Cynthia A.; Holm, Ingrid A.; Sanderson, Saskia C.; Garrison, Nanibaa’ A.; Sharp, Richard R.; Smith, Maureen E.; Kuivaniemi, Helena; Böttinger, Erwin P.; Connolly, John J.; Keating, Brendan J.; McCarty, Catherine A.; Williams, Marc S.; Jarvik, Gail P.

doi:10.3389/fgene.2014.00050

Cited by 39 publications

(44 citation statements)

References 31 publications

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“…78,79 Going forward the question will be not be whether patients will be tested, but what information will be provided, how it will be conveyed, and of course who will pay. 80,81 There is an ongoing debate regarding the return of incidental findings to patients, and which results are considered “actionable”.…”

Section: Barriers To Clinical Implementationmentioning

confidence: 99%

Pharmacogenetics in Cardiovascular Medicine

Tuteja

Limdi

2016

Curr Genet Med Rep

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Purpose of review Pharmacogenetics is an important component of precision medicine. Even within the genomic era, several challenges lie ahead in the road towards clinical implementation of pharmacogenetics in the clinic. This review will summarize the current state of knowledge regarding pharmacogenetics of cardiovascular drugs, focusing on those with the most evidence supporting clinical implementation- clopidogrel, warfarin and simvastatin. Recent findings There is limited translation of pharmacogenetics into clinical practice primarily due to the absence of outcomes data from prospective, randomized, genotype-directed clinical trials. There are several ongoing randomized controlled trials that will provide some answers as to the clinical utility of genotype-directed strategies. Several academic medical centers have pushed towards clinical implementation where the clinical validity data are strong. Their experiences will inform operational requirements of a clinical pharmacogenetics testing including the timing of testing, incorporation of test results into the electronic health record, reimbursement and ethical issues. Summary Pharmacogenetics of clopidogrel, warfarin and simvastatin are three examples where pharmacogenetics testing may provide added clinical value. Continued accumulation of evidence surrounding clinical utility of pharmacogenetics markers is imperative as this will inform reimbursement policy and drive adoption of pharamcogenetics into routine care.

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Section: Barriers To Clinical Implementationmentioning

confidence: 99%

Pharmacogenetics in Cardiovascular Medicine

Tuteja

Limdi

2016

Curr Genet Med Rep

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“…There is an increasing interest in incorporating findings of common disease risk alleles in the clinical setting [29,30]. Our study suggests the potential of translating results from previous GWAS for AAA for use in the clinical setting, to improve disease identification and risk stratification.…”

Section: Discussionmentioning

confidence: 91%

A multi-locus genetic risk score for abdominal aortic aneurysm

Austin

Schaid

et al. 2016

Atherosclerosis

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Background We investigated whether a multi-locus genetic risk scores (GRS) was associated with presence and progression of abdominal aortic aneurysm (AAA) in a case - control study. Methods and Results The study comprised of 1124 patients with AAA (74 ± 8 years, 83% men, 52% of them with a maximal AAA size ≤ 5 cm) and 6524 non-cases (67 ± 11 years, 58% men) from the Mayo Vascular Disease Biorepository. AAA was defined as infrarenal abdominal aorta diameter ≥3.0 cm or history of AAA repair. Non-cases were participants without known AAA. A GRS was calculated using 4 SNPs associated with AAA at genome-wide significance (P ≤ 10−8). The GRS was associated with the presence of AAA after adjustment for age, sex, cardiovascular risk factors, atherosclerotic cardiovascular diseases and family history of aortic aneurysm: odds ratio (OR, 95% confidence interval, CI) 1.06 (1.04 –1.09, p < 0.001). Adding GRS to conventional risk factors improved the association of presence of AAA (net reclassification index 14%, p < 0.001). In a subset of patients with AAA who had ≥2 imaging studies (n = 651, mean (SE) growth rate 2.47 (0.11) mm/year during a mean time interval of 5.41years), GRS, baseline size, diabetes and family history were each associated with aneurysm growth rate in univariate association (all p < 0.05). The estimated mean aneurysm growth rate was 0.50 mm/year higher in those with GRS > median (5.78) than those with GRS ≤ median (p = 0.01), after adjustment for baseline size (p < 0.001), diabetes (p = 0.046) and family history of aortic aneurysm (p = 0.02). Conclusions A multi-locus GRS was associated with presence of AAA and greater aneurysm expansion.

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“…Some institutions allow patients prior to testing to opt out of receiving incidental findings; others have used a staged-release of results to allow patients to focus on the most important findings first. 23 Institutions should consider their capacities and resources to manage IFs and the large swath of data generated by WGS/WES when choosing genomic tests.…”

Section: What Data To Store?mentioning

confidence: 99%

Pragmatic and Ethical Challenges of Incorporating the Genome into the Electronic Health Record

2014

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Recent successes in the use of gene sequencing for patient care highlight the potential of genomic medicine. For genomics to become a part of usual care, pertinent elements of a patient's genomic test must be communicated to the most appropriate care providers. Electronic medical records may serve as a useful tool for storing and disseminating genomic data. Yet, the structure of existing EMRs and the nature of genomic data pose a number of pragmatic and ethical challenges in their integration. Through a review of the recent genome-EMR integration literature, we explore concrete examples of these challenges, categorized under four key questions: What data will we store? How will we store it? How will we use it? How will we protect it? We conclude that genome-EMR integration requires a rigorous, multi-faceted and interdisciplinary approach of study. Problems facing the field are numerous, but few are intractable.

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Return of results in the genomic medicine projects of the eMERGE network

Cited by 39 publications

References 31 publications

Pharmacogenetics in Cardiovascular Medicine

Pharmacogenetics in Cardiovascular Medicine

A multi-locus genetic risk score for abdominal aortic aneurysm

Pragmatic and Ethical Challenges of Incorporating the Genome into the Electronic Health Record

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