Clinical outcomes of a genomic screening program for actionable genetic conditions

Abstract

Purpose Three genetic conditions—hereditary breast and ovarian cancer syndrome, Lynch syndrome, and familial hypercholesterolemia—have tier 1 evidence for interventions that reduce morbidity and mortality, prompting proposals to screen unselected populations for these conditions. We examined the impact of genomic screening on risk management and early detection in an unselected population. Methods Observational study of electronic health records (EHR) among individuals in whom a pathogenic/likely pathogenic variant in a tier 1 gene was discovered through Geisinger’s MyCode project. EHR of all eligible participants was evaluated for a prior genetic diagnosis and, among participants without such a diagnosis, relevant personal/family history, postdisclosure clinical diagnoses, and postdisclosure risk management. Results Eighty-seven percent of participants (305/351) did not have a prior genetic diagnosis of their tier 1 result. Of these, 65% had EHR evidence of relevant personal and/or family history of disease. Of 255 individuals eligible to have risk management, 70% ( n = 179) had a recommended risk management procedure after results disclosure. Thirteen percent of participants (41/305) received a relevant clinical diagnosis after results disclosure. Conclusion Genomic screening programs can identify previously unrecognized individuals at increased risk of cancer and heart disease and facilitate risk management and early cancer detection.

Genomic Screening Identifies Individuals at High Risk for Hereditary Transthyretin Amyloidosis

“…Over half sought follow-up care with a cardiologist within 8 months of result disclosure, and most of these individuals completed recommended cardiac evaluation. This is consistent with uptake observed in a genomic screening program for other actionable conditions, where 56% of participants with no prior knowledge of genomic risk followed up with a specialist referral and/or procedure [2]. In our study, follow-up specialist evaluations led to the identification of additional cardiac and non-cardiac phenotypes related to hATTR.…”

“…Population-based genomic screening is an emerging approach to uncover disease risk in unsuspecting individuals [ 1 ]. There is increasing evidence that genomic screening may identify and improve outcomes for certain medically actionable conditions for which preventive measures and/or effective treatments are available [ 2 , 3 ]. Genomic screening programs, typically performed in the setting of large health system clinics [ 4 ], biobanks [ 2 ], or public health initiatives [ 3 ], may choose to return medically actionable findings with varying degrees of clinical utility.…”

“…There is increasing evidence that genomic screening may identify and improve outcomes for certain medically actionable conditions for which preventive measures and/or effective treatments are available [ 2 , 3 ]. Genomic screening programs, typically performed in the setting of large health system clinics [ 4 ], biobanks [ 2 ], or public health initiatives [ 3 ], may choose to return medically actionable findings with varying degrees of clinical utility. Recent studies have found that most individuals at genomic risk for medically actionable conditions are unaware of their risk [ 5 , 6 , 7 ], and that the majority of individuals informed of such risk will undergo recommended surveillance or risk-reducing interventions [ 2 , 8 ].…”

“…Genomic screening programs, typically performed in the setting of large health system clinics [ 4 ], biobanks [ 2 ], or public health initiatives [ 3 ], may choose to return medically actionable findings with varying degrees of clinical utility. Recent studies have found that most individuals at genomic risk for medically actionable conditions are unaware of their risk [ 5 , 6 , 7 ], and that the majority of individuals informed of such risk will undergo recommended surveillance or risk-reducing interventions [ 2 , 8 ]. Therefore, genomic screening holds the promise of identifying preventable and treatable diseases that may be otherwise missed in routine clinical care.…”

Leveraging population‐based exome screening to impact clinical care: The evolution of variant assessment in the Geisinger MyCode research project

“…While population‐scale genomic screening poses new challenges compared to current patient‐level approaches in the diagnostic setting, much of the literature on population‐scale screening has focused on recruitment, consent, clinical utility, and results disclosure (Buchanan et al, 2020; Grzymski et al, 2020; Hao et al, 2020; Ilori et al, 2020; Murray et al, 2018; Schwartz et al, 2018). Little attention has been given to the operational challenges of evaluating genomic data at a population‐scale.…”