Clinical Outcomes of a Genomic Screening Program for Actionable Genetic Conditions

Buchanan, Adam H.; Kirchner, H. Lester; Schwartz, Marci; Kelly, Melissa; Schmidlen, Tara; Jones, Laney K.; Hallquist, Miranda L. G.; Rocha, Heather; Betts, Megan; Schwiter, Rachel; Butry, Loren; Lazzeri, Amanda L.; Frisbie, Lauren R.; Rahm, Alanna Kulchak; Hao, Jing; Willard, Huntington F.; Martin, Christa Lese; Ledbetter, David H.; Williams, Marc S.; Sturm, Amy C.

doi:10.1097/01.ogx.0000743356.15320.79

Cited by 5 publications

(5 citation statements)

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“…Recent DNA‐screening programs in the US 1,17 have been made available only to individuals within certain health care networks, living in certain locations (eg, the Healthy Nevada Project in Nevada, and the Geisinger MyCode project in Pennsylvania), and not via a public health care system. This selective approach has not ensured equity of access — a fundamental principle of population‐level screening 7 .…”

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confidence: 99%

Population DNA screening for medically actionable disease risk in adults

Lacaze

Tiller

Winship

et al. 2022

Medical Journal of Australia

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confidence: 99%

Population DNA screening for medically actionable disease risk in adults

Lacaze

Tiller

Winship

et al. 2022

Medical Journal of Australia

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“…The identification of the LPL and LDLR variants in this cohort may also represent underdiagnosis of hyperlipidemia in underrepresented populations in genomic medicine 22 and advocates for a population genomics approach, specifically for FH. 23 In particular, we noted that FH as a single ICC group dominated the catalog of LP/P ICC gene variants in this cohort. Indeed, it is estimated that the prevalence of FH in Singapore is 1 in 250, and nonetheless still significantly underdiagnosed.…”

Section: Discussionmentioning

confidence: 66%

Causative Variants for Inherited Cardiac Conditions in a Southeast Asian Population Cohort

Tomar

Klinzing

Chen

et al. 2022

Circ: Genomic and Precision Medicine

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Background: Variable penetrance and late-onset phenotypes are key challenges for classifying causal as well as incidental findings in inherited cardiac conditions. Allele frequencies of variants in ancestry-specific populations, along with clinical variant analysis and interpretation, are critical to determine their true significance. Methods: Here, we carefully reviewed and classified variants in genes associated with inherited cardiac conditions based on a population whole-genome sequencing cohort of 4810 Singaporeans representing Southeast Asian ancestries. Results: Eighty-nine (1.85%) individuals carried either pathogenic or likely pathogenic variants across 25 genes. 51.7% had variants in causal genes for familial hyperlipidemia, but there were also recurrent variants in SCN5A and MYBPC3 , causal genes for inherited arrhythmia and cardiomyopathy, which, despite previous reports, we determined to lack criteria for pathogenicity. Conclusions: Our findings highlight the incidence of disease-related variants in inherited cardiac conditions and emphasize the value of large-scale sequencing in specific ancestries. Follow-up detailed phenotyping and analysis of pedigrees are crucial because assigning pathogenicity will significantly affect clinical management for individuals and their family members.

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“…In comparison, Geisinger analyzed genetic counseling visits across return of genomic risk results for all conditions returned through MyCode and found a higher uptake of genetic counseling visits (55.3%) in other conditions. 30 However, when pre- and postdisclosure genetic counseling was integrated into a multidisciplinary lipid clinic for FH at Geisinger, almost all participants opted for the visit. 25 One potential reason for lower uptake of genetic counseling in this study could be the requirement of scheduling and completing an additional visit, supporting the integration of genetic counseling services into other specialty care.…”

Section: Discussionmentioning

confidence: 99%

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

Jones

Chen

Hassen

et al. 2022

Circ: Genomic and Precision Medicine

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BACKGROUND: Limited information is available regarding clinician and participant behaviors after disclosure of genomic risk variants for familial hypercholesterolemia (FH) from a population genomic screening program. METHODS: We conducted a retrospective cohort study of MyCode participants with an FH risk variant beginning 2 years before disclosure until January 16, 2019. We analyzed lipid-lowering prescriptions (clinician behavior), medication adherence (participant behavior), and LDL (low-density lipoprotein) cholesterol levels (health outcome impact) pre- and post-disclosure. Data were collected from electronic health records and claims. RESULTS: The cohort included 96 participants of mean age 57 (22–90) years with median follow-up of 14 (range, 3–39) months. Most (90%) had a hypercholesterolemia diagnosis but no specific FH diagnosis before disclosure; 29% had an FH diagnosis post-disclosure. After disclosure, clinicians made 36 prescription changes in 38% of participants, mostly in participants who did not achieve LDL cholesterol goals pre-disclosure (81%). However, clinicians wrote prescriptions for fewer participants post-disclosure (71/96, 74.0%) compared with pre-disclosure (81/96, 84.4%); side effects were documented for most discontinued prescriptions (23/25, 92%). Among the 16 participants with claims data, medication adherence improved (proportion of days covered pre-disclosure of 70% [SD, 24.7%] to post-disclosure of 79.1% [SD, 27.3%]; P =0.05). Among the 52 (54%) participants with LDL cholesterol values both before and after disclosure, average LDL cholesterol decreased from 147 to 132 mg/dL ( P =0.003). CONCLUSIONS: Despite disclosure of an FH risk variant, nonprescribing and nonadherence to lipid-lowering therapy remained high. However, when clinicians intensified medication regimens and participants adhered to medications, lipid levels decreased.

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Clinical Outcomes of a Genomic Screening Program for Actionable Genetic Conditions

Cited by 5 publications

References 0 publications

Population DNA screening for medically actionable disease risk in adults

Population DNA screening for medically actionable disease risk in adults

Causative Variants for Inherited Cardiac Conditions in a Southeast Asian Population Cohort

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

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