JAMA Netw Open. 2026 Jul 1;9(7):e2622743. doi: 10.1001/jamanetworkopen.2026.22743.
ABSTRACT
IMPORTANCE: Genomic screening for Centers for Disease Control and Prevention Tier 1 conditions, ie, hereditary breast and ovarian cancer syndrome (HBOC), Lynch syndrome, and familial hypercholesterolemia, enables early detection of these rare, but highly penetrant disorders and supports timely, evidence-based interventions. However, states with large rural and socially disadvantaged populations, such as South Carolina, face substantial structural and access-related barriers that limit the reach of population-wide genomic screening (PWGS).
OBJECTIVE: To examine whether combining implementation science and informatics infrastructure supports PWGS and to assess screening coverage and positivity by rurality and social disadvantage.
DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used data from In Our DNA SC, a statewide PWGS program launched on November 8, 2021, in South Carolina. Recruitment and sample collection occurred via the health system, community-based collection events, and at-home kits. Analyses included adults aged 18 or older who completed screening as of July 23, 2025.
EXPOSURE: Genomic screening for Centers for Disease Control and Prevention Tier 1 conditions.
MAIN OUTCOMES AND MEASURES: County-level screening coverage rates (per 100 000 population) and positivity prevalence (per 100 000 valid results) were stratified using rural-urban continuum (RUC) codes (1 = most urban to 9 = most rural) and Social Vulnerability Index (SVI) quartiles (from 1 = least disadvantaged to 4 = most disadvantaged).
RESULTS: Of a total of 82 420 adults enrolled in the PWGS program, 50 897 completed screening (71.6% aged <65 years and 28.4% aged ≥65 years, 72.6% female). The program enrolled and screened participants from all 46 South Carolina counties. Screening coverage rates varied by RUC code and SVI. Screening rates per 100 000 population exceeded 1000 in RUC codes 1 through 3 and were significantly higher than RUC code 6 (791.4; 95% CI, 757.1-827.2), RUC code 8 (861.4; 95% CI, 801.1-926.2), and RUC code 9 (839.6; 95% CI, 683.6-1030.8). Screening coverage by overall SVI score was significantly higher in quartile 1 (1422.1; 95% CI, 1406.3-1438.1) and quartile 2 (1188.4; 95% CI, 1167.3-1209.9) compared with quartile 3 (888.4; 95% CI, 866.5-910.9) and quartile 4 (839.6; 95% CI, 952.3-1025.4). Positivity prevalence was generally similar across RUC codes, except for HBOC, which was significantly higher per 100 000 in RUC code 2 (801.3; 95% CI, 715.3-897.4) compared with RUC code 1 (268.5; 95% CI, 123.1-584.5). When examined by overall SVI quartiles, positivity prevalence for HBOC, Lynch syndrome, and familial hypercholesterolemia remained consistent, with no statistically significant differences across levels of disadvantage.
CONCLUSIONS AND RELEVANCE: This cross-sectional study of a statewide PWGS program supported by an implementation framework and informatics platform suggests broad geographic and social reach. Evaluation of clinical and behavioral outcomes is the critical next step for determining program effectiveness and performance in community and clinical settings. Taken together, these findings suggest that pairing implementation science with robust informatics infrastructure may support PWGS delivery in diverse communities.
PMID:42440321 | DOI:10.1001/jamanetworkopen.2026.22743
