The purpose of the Million Veteran Program- Return of Actionable Results (MVP-ROAR) Study is to develop a process to return medically actionable genetic results to living MVP participants nationwide and to determine the impact of doing so on medical management and outcomes and Veteran quality of life.

The Million Veteran Program - Return of Actionable Results (MVP-ROAR) Study is a randomized controlled trial of immediate vs. delayed (after 6 months) return of medically actionable, clinically confirmed genetic testing results. MVP participants with a medically actionable variant in their MVP chip genotype data will be contacted and offered the opportunity to receive clinical confirmation of this result through a research protocol. First, a non-randomized pilot trial will be conducted among 10 eligible MVP participants, followed by a randomized controlled trial of immediate vs. delayed clinical confirmation and reporting, delivered to participants nationwide via telegenetic counseling.

Three hypotheses will be tested:

Hypothesis 1 (LDL-C change): LDL-C reduction after 6 months will be greater in the Immediate Results arm compared to the Delayed Results arm (primary outcome) Hypothesis 2 (LDL-C target): The proportion of participants meeting clinically significant LDL-C targets (<100mg/dL for primary prevention and <70 mg/dL for secondary prevention) at 6 months will be greater in the Immediate Results arm than in the Delayed Results arm (secondary outcome) Hypothesis 3 (Pharmacotherapy): the proportion of participants with an intensification of lipid-lowering pharmacotherapy will be greater in the Immediate Results arm than in the Delayed Results arm (secondary outcome)

Inclusion Criteria:

• Living enrollee in MVP
• Is identified to have a pathogenic or likely pathogenic variant in the gene(s) of interest in MVP genotype data

Exclusion Criteria:

• Previously underwent genetic testing for the condition of interest
• Is incarcerated
• Is pregnant

We will share de-identified individual-level trial data through a data repository housed on a secure VA server and accessible only to outside investigators with IRB and other regulatory approvals. MVP ROAR Study data will also be stored in the VA MVP Central Database.

Death, serious adverse events, and other (non-serious adverse events) were not systematically assessed for the study.

Limitations include:

1. Lower enrollment than planned
2. Baseline LDL-C values were carried forward for 15 participants missing their 6-month value
3. Participants with variants only detectable by sequencing were not included
4. LDL-C is a surrogate endpoint for long-term clinical outcomes