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Item A Polygenic Resilience Score Moderates the Genetic Risk for Schizophrenia: Replication in 18,090 Cases and 28,114 Controls from the Psychiatric Genomics Consortium(Wiley, 2024) Hess, Jonathan L.; Mattheisen, Manuel; Schizophrenia Working Group of the Psychiatric Genomics Consortium; Greenwood, Tiffany A.; Tsuang, Ming T.; Edenberg, Howard J.; Holmans, Peter; Faraone, Stephen V.; Glatt, Stephen J.; Biochemistry and Molecular Biology, School of MedicineIdentifying heritable factors that moderate the genetic risk for schizophrenia (SCZ) could help clarify why some individuals remain unaffected despite having relatively high genetic liability. Previously, we developed a framework to mine genome-wide association (GWAS) data for common genetic variants that protect high-risk unaffected individuals from SCZ, leading to derivation of the first-ever "polygenic resilience score" for SCZ (resilient controls n = 3786; polygenic risk score-matched SCZ cases n = 18,619). Here, we performed a replication study to verify the moderating effect of our polygenic resilience score on SCZ risk (OR = 1.09, p = 4.03 × 10-5 ) using newly released GWAS data from 23 independent case-control studies collated by the Psychiatric Genomics Consortium (PGC) (resilient controls n = 2821; polygenic risk score-matched SCZ cases n = 5150). Additionally, we sought to optimize our polygenic resilience-scoring formula to improve subsequent modeling of resilience to SCZ and other complex disorders. We found significant replication of the polygenic resilience score, and found that strict pruning of SNPs based on linkage disequilibrium to known risk SNPs and their linked loci optimizes the performance of the polygenic resilience score.Item Differences in Provider Hepatitis C Virus Screening Recommendations by Patient Risk Status(Elsevier, 2024-01-09) Laily, Alfu; Duncan, Robert; Gabhart, Kaitlyn M.; Nephew, Lauren D.; Christy, Shannon M.; Vadaparampil, Susan T.; Giuliano, Anna R.; Kasting, Monica L.; Medicine, School of MedicineProviders' recommendation is among the strongest predictors to patients engaging in preventive care. Therefore, the aim of this study was to compare providers' Hepatitis C Virus (HCV) screening recommendation quality between high-risk and average-risk patients to determine if providers are universally recommending HCV screening, regardless of risk behaviors. This cross-sectional survey of 284 Indiana providers in 2020 assessed provider characteristics, HCV screening recommendation practices (strength, presentation, frequency, timeliness), self-efficacy, and barriers to recommending HCV screening. T-test and Chi-square compared recommendation practices for high-risk and average-risk patients. Prevalence ratios were calculated for variables associated with HCV recommendation strength comparing high-risk and average-risk patients. Logistic regression analyses examined factors associated with HCV recommendation strength for high- and average-risk patients, with odds ratios. Compared to average-risk patients, high-risk patients received higher proportion of HCV recommendations that were strong (70.4 % v. 42.4 %), routine (61.9 % v. 55.6 %), frequent (37.7 % v. 28 %), and timely (74.2 % v. 54.9 %) (P-values < 0.001). Compared to average-risk patients, providers with high-risk patients had a lower percentage of giving a strong recommendation if they were nurse practitioner (PR = 0.49). For high-risk patients, providers with higher self-efficacy (aOR = 2.16;95 %CI = 0.99-4.69) had higher odds, while those with higher perceived barriers (aOR = 0.19;95 %CI = 0.09-0.39) and those with an internal medicine specialty compared to family medicine (aOR = 0.22;95 %CI = 0.08-0.57) had lower odds of giving a strong recommendation. These data suggest providers are not universally recommending HCV screening for all adults regardless of reported risk. Future research should translate these findings into multilevel interventions to improve HCV screening recommendations regardless of patient risk status.