Impact of a Population Genomic Screening Program on Health Behaviors Related to Familial Hypercholesterolemia Risk Reduction

Jones, Laney K.; Chen, Nan; Hassen, Dina; McMinn, Megan; Klinger, Tracey; Hartzel, Dustin N.; Veenstra, David L.; Spencer, Scott J.; Snyder, Susan; Peterson, Josh F.; Schlieder, Victoria; Sturm, Amy C.; Gidding, Samuel S.; Williams, Marc S.; Hao, Jing

doi:10.1161/circgen.121.003549

Cited by 5 publications

(4 citation statements)

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“…Different biobank studies have used different models of return of genetic results to participants. [26][27][28] The clinical and research regulatory environment of MVP and VHA and the national landscape of primary care and genetic consultative services in the VHA shaped the model selected for the MVP-ROAR-FH Study.…”

Section: Modeling Return Of Genetic Research Results In Vhamentioning

confidence: 99%

“…Other initiatives have identified actionable FH-associated variants among biobanks participants and implemented processes to return results to participants, including the Geisinger Health System MyCode Community Health Initiative and 7 sites in the Electronic Medical Records and Genomics network. [26][27][28] In contrast to local or regional health system-linked programs, the MVP-ROAR-FH Study is national in scope. At the same time, unlike national initiatives like the All of Us Research Program, 54 MVP's position within the single largest US healthcare system creates the opportunity and perhaps expectation that important results will be integrated into The MVP-ROAR-FH Study pilot phase experience supports the following recommendations for the future of return of genetic results in MVP and other similar programs.…”

Section: Discussionmentioning

confidence: 99%

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Introducing return of results in the Million Veteran Program: Design and pilot results of the MVP-ROAR Familial Hypercholesterolemia Study

Vassy,

Brunette,

et al. 2023

Preprint

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BackgroundAs a mega-biobank linked to a national healthcare system, the Million Veteran Program (MVP) can directly improve the health care and health outcomes of participants. Return of genetic research results at this scale presents challenges and complexities.MethodsTo determine the feasibility and outcomes of returning medically actionable genetic results to MVP participants, the program launched the MVP Return Of Actionable Results (MVP-ROAR) Study, with familial hypercholesterolemia (FH) as the exemplar actionable condition. The MVP-ROAR-FH Study consists of a completed pilot phase and an ongoing randomized clinical trial (RCT), in which MVP participants are recontacted and invited to receive clinical confirmatory gene sequencing testing and a telegenetic counseling intervention. The primary outcome of the RCT is 6-month change in low-density lipoprotein cholesterol (LDL-C) between participants receiving results at baseline and those receiving results after 6 months.ResultsNine MVP participants suspected to have a pathogenic variant inlow-density lipoprotein receptor(LDLR) enrolled in the single-arm pilot phase of the study; one was lost to follow-up prior to confirmatory testing. Clinical sequencing confirmed the pathogenic variant for 5 of the remaining 8 participants. Six-month ΔLDL-C among enrollees after the genetic counseling intervention was −37 mg/dL (95% CI: −12 to −61;p=0.03).ConclusionsWhile underscoring the importance of analytic validity and clinical confirmation of research results, the pilot phase of the MVP-ROAR-FH Study demonstrates the feasibility of a protocol to return genetic results to MVP participants and their providers. The ongoing RCT will contribute to understanding of how such a program might improve patient health care and outcomes.

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Section: Modeling Return Of Genetic Research Results In Vhamentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Introducing return of results in the Million Veteran Program: Design and pilot results of the MVP-ROAR Familial Hypercholesterolemia Study

Vassy,

Brunette,

et al. 2023

Preprint

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“…While our observations suggest potential utility of RoR for FH-associated P/LP variants, costs and health care utilization consequent to RoR need further study, although some early results are beginning to appear. 30 Population genomic screening of young adults for Tier 1 cancer related genes was found to be cost-effective partly due to reduction in mortality. 31 For FH, one study did not find genetic screening to be cost-effective compared with lipid profile screening along with statin adherence measures.…”

Section: Discussionmentioning

confidence: 99%

Familial Hypercholesterolemia in the Electronic Medical Records and Genomics Network: Prevalence, Penetrance, Cardiovascular Risk, and Outcomes After Return of Results

Dikilitas

Sherafati

Saadatagah

et al. 2023

Circ: Genomic and Precision Medicine

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BACKGROUND: The implications of secondary findings detected in large-scale sequencing projects remain uncertain. We assessed prevalence and penetrance of pathogenic familial hypercholesterolemia (FH) variants, their association with coronary heart disease (CHD), and 1-year outcomes following return of results in phase III of the electronic medical records and genomics network. METHODS: Adult participants (n=18 544) at 7 sites were enrolled in a prospective cohort study to study the clinical impact of returning results from targeted sequencing of 68 actionable genes, including LDLR , APOB , and PCSK9 . FH variant prevalence and penetrance (defined as low-density lipoprotein cholesterol >155 mg/dL) were estimated after excluding participants enrolled on the basis of hypercholesterolemia. Multivariable logistic regression was used to estimate the odds of CHD compared to age- and sex-matched controls without FH-associated variants. Process (eg, referral to a specialist or ordering new tests), intermediate (eg, new diagnosis of FH), and clinical (eg, treatment modification) outcomes within 1 year after return of results were ascertained by electronic health record review. RESULTS: The prevalence of FH-associated pathogenic variants was 1 in 188 (69 of 13,019 unselected participants). Penetrance was 87.5%. The presence of an FH variant was associated with CHD (odds ratio, 3.02 [2.00–4.53]) and premature CHD (odds ratio, 3.68 [2.34–5.78]). At least 1 outcome occurred in 92% of participants; 44% received a new diagnosis of FH and 26% had treatment modified following return of results. CONCLUSIONS: In a multisite cohort of electronic health record–linked biobanks, monogenic FH was prevalent, penetrant, and associated with presence of CHD. Nearly half of participants with an FH-associated variant received a new diagnosis of FH and a quarter had treatment modified after return of results. These results highlight the potential utility of sequencing electronic health record–linked biobanks to detect FH.

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“…Additionally, FH genetic testing has been shown to have a positive impact on the initiation of lipidlowering therapy, adherence to therapy, and LDL-C reduction [3,[26][27][28]. In a study 747 individuals with FH in the Netherlands, the percentage of treated patients increased from 37.6% to 85.9% two years after genetic testing [27].…”

Section: Clinical Utility Of Genetic Testing For Familial Hypercholes...mentioning

confidence: 99%

Genetic testing for familial hypercholesterolemia

Zhang,

de Ferranti,

Moran

2024

Current Opinion in Lipidology

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Purpose of review Despite familial hypercholesterolemia (FH) being the most common genetic cause of cardiovascular disease (CVD), genetic testing is rarely utilized in the US. This review summarizes what is known about the clinical utility of genetic testing and its role in the diagnosis and screening of FH. Recent findings The presence of an FH-causative variant is associated with a substantially higher risk of CVD, even when low-density lipoprotein cholesterol (LDL-C) levels are only modestly elevated. Genetic testing can facilitate the identification of FH cases who may be missed by clinical diagnostic criteria, improve risk stratification beyond LDL-C and family history, guide treatment decisions, and improve treatment initiation and adherence. Genetic testing can be incorporated into FH screening and diagnosis algorithms, including cascade, targeted, and universal screening. Integrating genetic testing into cascade screening can enhance the effectiveness of the process. Several models of universal FH screening with coordinated genetic and lipid testing are feasible and effective. Summary More systematic integration of genetic testing into FH diagnosis and screening can significantly reduce the burden of this condition through early detection and treatment. Further pragmatic implementation studies are needed to determine how to more effectively and affordably integrate genetic testing into clinical lipid screening programs.

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Impact of a Population Genomic Screening Program on Health Behaviors Related to Familial Hypercholesterolemia Risk Reduction

Cited by 5 publications

References 45 publications

Introducing return of results in the Million Veteran Program: Design and pilot results of the MVP-ROAR Familial Hypercholesterolemia Study

Introducing return of results in the Million Veteran Program: Design and pilot results of the MVP-ROAR Familial Hypercholesterolemia Study

Familial Hypercholesterolemia in the Electronic Medical Records and Genomics Network: Prevalence, Penetrance, Cardiovascular Risk, and Outcomes After Return of Results

Genetic testing for familial hypercholesterolemia

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