Biomedical subjects

Richard R Sharp

Publications and source records attributed to Richard R Sharp.

3 recordsLinked to original sources

PubMed2026

A workshop considering genetic research and data collection with American Indian and Alaska Native people outside of Tribal jurisdiction.

INTRODUCTION: In the United States (US), Tribes are sovereign nations and have the right to oversee research conducted with Tribal citizens. However, it is unclear who should approve research protocols when data from American Indian and Alaska Native (AIAN) people are collected off Tribal lands. As genetic research continues to advance and transform the delivery of healthcare, equitable inclusion of AIAN people is necessary, but oversight of research needs clarity. METHODS: We held a 3-day workshop with US thought leaders on genetic and other health research with AIAN people in urban areas to explore views and values on this issue and to discuss potential policy and practice solutions. RESULTS: Thirty-six individuals attended. Solidarity surfaced as a foundational motivation for Tribal Nations to review research conducted with AIAN people, whether on Tribal lands or not. Understanding data from Indigenous perspectives was identified as a way to ensure appropriate AIAN community protections are in place. Three discrete areas to improve policy were suggested-Tribal, Academic Institution, and National-to protect AIAN people participating in research both on and off Tribal lands. DISCUSSION: Researchers, whether Indigenous or not, must recognize Tribal sovereignty and operate in solidarity with the applicable and most appropriate ethical principles and regulations.

Alaska Native↗

PubMed2026

Additive value of polygenic risk and family history for coronary heart disease risk stratification in two diverse US cohorts.

Whether polygenic risk, monogenic familial hypercholesterolemia (FH), and family history (FamHx) are additively informative for coronary heart disease (CHD) risk prediction across self-identified race/ethnicity (SIRE) groups has not been established. In two diverse cohorts-Electronic Medical Records and Genomics (eMERGE) phase IV (eIV; n = 19,348) and All of Us (AoU; n = 239,645)-we quantified the associations of a polygenic risk score (PRSCHD), pathogenic/likely pathogenic variants in genes associated with FH, and FamHx with CHD and evaluated their incremental value when added to the pooled cohort equations (PCEs). CHD was defined as myocardial infarction, unstable angina, or coronary revascularization. We modeled associations with multivariable logistic regression (prevalent CHD in eIV) and Cox proportional hazards (incident CHD in AoU) and characterized predictive performance with the c-statistic and reclassification and decision-curve net benefits across actionable 10-year risk thresholds. The effects of PRSCHD and FamHx were independent and additive in both cohorts and consistent across White, Black, and Latino SIRE groups. In eIV, adding PRSCHD and FamHx to the PCE increased the c-statistic for prevalent CHD from 0.719 to 0.753 (p-diff = 9.1 × 10-3) and reclassified 18.8% of participants at the 7.5% 10-year threshold, yielding approximately 4 additional true-positive CHD identifications per 1,000 screened. Net benefit gains were observed between the 7.5% and 10% thresholds across all three SIRE groups. In conclusion, PRSCHD and FamHx were independently and additively associated with CHD across major SIRE groups in two diverse cohorts in the United States (US), motivating the addition of these factors to clinical risk algorithms.

Humans↗

PubMed2026

Implementing a Multi-Ancestry Polygenic Risk Score for Coronary Heart Disease in a Diverse Cohort.

PURPOSE: We describe a prospective cohort study (NCT05277116) conducted in phase IV of the electronic MEdical Records and GEnomics (eMERGE) Network to implement a multi-ancestry polygenic risk score for coronary heart disease (PRSCHD: PGS004696) and assess outcomes after return of results (RoR). METHODS: PRSCHD was considered alongside family history (FamHxCHD), monogenic risk from familial hypercholesterolemia (FH), and clinical risk factors, to return CHD risk as part of a Genome Informed Risk Assessment (GIRA) report. Participants with high PRSCHD (top 5th percentile) or FH received their results from study personnel, while participants with FamHxCHD were informed by mail/email. Results were placed in the electronic health record and communicated to the primary care provider. The primary outcome of initiation/intensification of lipid lowering therapy within 12 months after RoR is compared between participants with PRSCHD ≥95th percentile and those with PRSCHD 90th-94th percentile, using a regression discontinuity design. Secondary outcomes include ordering of screening tests, a new CHD diagnosis, and lifestyle changes. RESULTS: By April 2025, 20,421 adults were enrolled: mean age 50±15 years (range 18-75 years), 68% female, 50% belonging to health disparity groups, and 40% non-White by self-report. Prevalence of CHD, FamHxCHD, high PRSCHD and FH was 4.0%, 10.2%, 4.3% and 0.7%, respectively; 14.3% had at least one of the three CHD genetic risk factors and CHD risk estimates were highest in those who self-reported as Black. CONCLUSION: The prevalence of increased genetic risk for CHD was high and at least one of the three genetic risk factors for CHD was present in 14.2% of the cohort. Analyses are underway to assess outcomes after PRSCHD implementation in the context of FamHxCHD, FH, and clinical risk, across the age spectrum in a diverse cohort.

PRS↗