The NYCKidSeq randomized controlled trial: Impact of GUÍA digitally enhanced genetic results disclosure in diverse families.

Digital solutions are needed to support rapid increases in the application of genetic/genomic tests (GTs) in diverse clinical settings and patient populations. We developed GUÍA, a bilingual digital application that facilitates disclosure of GT results. The NYCKidSeq randomized controlled trial enrolled diverse children with neurologic, cardiac, and immunologic conditions who underwent GTs. The trial evaluated GUÍA's impact on understanding the GT results by randomizing families to results disclosure genetic counseling with GUÍA (intervention) or standard of care (SOC). Parents/legal guardians (participants) completed surveys at baseline, post-results disclosure, and 6 months later. Survey measures assessed the primary study outcomes of participants' perceived understanding of and confidence in explaining their child's GT results and the secondary outcome of objective understanding. The analysis included 551 diverse participants, 270 in the GUÍA arm and 281 in SOC. Participants in the GUÍA arm had significantly higher perceived understanding post-results (OR = 2.8, CI[1.004, 7.617], p = 0.049) and maintained higher objective understanding over time (OR = 1.1, CI[1.004, 1.127], p = 0.038) compared to SOC. There was no impact on perceived confidence. Hispanic/Latino(a) individuals in the GUÍA arm maintained higher perceived understanding (OR = 3.9, CI[1.603, 9.254], p = 0.003), confidence (OR = 2.7, CI[1.021, 7.277], p = 0.046), and objective understanding (OR = 1.1, CI[1.009, 1.212], p = 0.032) compared to SOC. This trial demonstrates that GUÍA positively impacts understanding of GT results in diverse parents of children with suspected genetic conditions and builds a case for utilizing GUÍA to deliver complex results. Continued development and evaluation of digital applications in diverse populations are critical for equitably scaling GT offerings in specialty clinics.

Genetic variation in the human leukocyte antigen region confers susceptibility to Clostridioides difficile infection.

Clostridioides difficile (C. diff.) infection (CDI) is a leading cause of hospital acquired diarrhea in North America and Europe and a major cause of morbidity and mortality. Known risk factors do not fully explain CDI susceptibility, and genetic susceptibility is suggested by the fact that some patients with colons that are colonized with C. diff. do not develop any infection while others develop severe or recurrent infections. To identify common genetic variants associated with CDI, we performed a genome-wide association analysis in 19,861 participants (1349 cases; 18,512 controls) from the Electronic Medical Records and Genomics (eMERGE) Network. Using logistic regression, we found strong evidence for genetic variation in the DRB locus of the MHC (HLA) II region that predisposes individuals to CDI (P > 1.0 × 10-14; OR 1.56). Altered transcriptional regulation in the HLA region may play a role in conferring susceptibility to this opportunistic enteric pathogen.

Parent-Reported Clinical Utility of Pediatric Genomic Sequencing.

BACKGROUND AND OBJECTIVES: Genomic sequencing (GS) is increasingly used for diagnostic evaluation, yet follow-up care is not well understood. We assessed clinicians' recommendations after GS, parent-reported follow-up, and actions parents initiated in response to learning their child's GS results. METHODS: We surveyed parents of children who received GS through the Clinical Sequencing Evidence Generating Research consortium ∼5 to 7 months after return of results. We compared the proportion of parents who reported discussing their child's result with a clinician, clinicians' recommendations, and parents' follow-up actions by GS result type using χ2 tests. RESULTS: A total of 1188 respondents completed survey measures on recommended medical actions (n = 1187) and/or parent-initiated actions (n = 913). Most parents who completed recommended medical actions questions (n = 833, 70.3%) reported having discussed their child's GS results with clinicians. Clinicians made recommendations to change current care for patients with positive GS results (n = 79, 39.1%) more frequently than for those with inconclusive (n = 31, 12.4%) or negative results (n = 44, 11.9%; P < .001). Many parents discussed (n = 152 completed, n = 135 planned) implications of GS results for future pregnancies with a clinician. Aside from clinical recommendations, 13.0% (n = 119) of parents initiated changes to their child's health or lifestyle. CONCLUSIONS: In diverse pediatric clinical contexts, GS results can lead to recommendations for follow-up care, but they likely do not prompt large increases in the quantity of care received.

The NYCKidSeq randomized controlled trial: Impact of GUÍA digitally enhanced genetic counseling in racially and ethnically diverse families.

Background: Digital solutions are needed to support rapid increases in the application of genetic and genomic tests (GT) in diverse clinical settings and patient populations. We developed GUÍA, a bi-lingual web-based platform that facilitates disclosure of GT results. The NYCKidSeq randomized controlled trial evaluated GUÍA's impact on understanding of GT results. Methods: NYCKidSeq enrolled diverse children with neurologic, cardiac, and immunologic conditions who underwent GT. Families were randomized to genetic counseling with GUÍA (intervention) or standard of care (SOC) genetic counseling for results disclosure. Parents/legal guardians (participants) completed surveys at baseline, post-results disclosure, and 6-months later. Survey measures assessed the primary study outcomes of perceived understanding of and confidence in explaining their child's GT results and the secondary outcome of objective understanding. We used regression models to evaluate the association between the intervention and the study outcomes. Results: The analysis included 551 participants, 270 in the GUÍA arm and 281 in SOC. Participants' mean age was 41.1 years and 88.6% were mothers. Most participants were Hispanic/Latino(a) (46.3%), White/European American (24.5%), or Black/African American (15.8%). Participants in the GUÍA arm had significantly higher perceived understanding post-results (OR=2.8, CI[1.004,7.617], P=0.049) and maintained higher objective understanding over time (OR=1.1, CI[1.004, 1.127], P=0.038) compared to those in the SOC arm. There was no impact on perceived confidence. Hispanic/Latino(a) individuals in the GUÍA arm maintained higher perceived understanding (OR=3.9, CI[1.6, 9.3], P=0.003), confidence (OR=2.7, CI[1.021, 7.277], P=0.046), and objective understanding (OR=1.1, CI[1.009, 1.212], P=0.032) compared to SOC . Conclusions: This trial demonstrates that GUÍA positively impacts understanding of GT results in diverse parents of children with suspected genetic conditions. These findings build a case for utilizing GUÍA to deliver complex and often ambiguous genetic results. Continued development and evaluation of digital applications in diverse populations are critical for equitably scaling GT offerings in specialty clinics. Trial Registration: Clinicaltrials.gov identifier NCT03738098.