Search

In studies of individuals of primarily European genetic ancestry, common and low-frequency variants and rare coding variants have been found to be associated with the risk of bipolar disorder (BD) and schizophrenia (SZ). However, less is known for individuals of other genetic ancestries or the role of rare non-coding variants in BD and SZ risk. We performed whole genome sequencing of African American individuals: 1,598 with BD, 3,295 with SZ, and 2,651 unaffected controls (InPSYght study). We increased power by incorporating 14,812 jointly called psychiatrically unscreened ancestry-matched controls from the Trans-Omics for Precision Medicine (TOPMed) Program for a total of 17,463 controls. To identify variants and sets of variants associated with BD and/or SZ, we performed single-variant tests, gene-based tests for singleton protein truncating variants, and rare and low-frequency variant annotation-based tests with conservation and universal chromatin states and sliding windows. We found suggestive evidence of BD association with single-variants on chromosome 18 and of lower BD risk associated with rare and low-frequency variants on chromosome 11 in a region with multiple BD GWAS loci, using a sliding window approach. We also found that chromatin and conservation state tests can be used to detect differential calling of variants in controls sequenced at different centers and to assess the effectiveness of sequencing metric covariate adjustments. Our findings reinforce the need for continued whole genome sequencing in additional samples of African American individuals and more comprehensive functional annotation of non-coding variants.

Cannabinoid hyperemesis syndrome is an underrecognized condition associated with recurrent vomiting and abdominal pain in individuals with prolonged cannabis use. This study used an internet-based survey targeting individuals with self-reported cannabinoid hyperemesis syndrome to assess the burden of disease and to examine associations between heavy cannabis use, early initiation of cannabis use, and cannabinoid hyperemesis syndrome episode frequency. A total of 1,052 participants were included, with the majority reporting frequent cannabis use and significant health care utilization, including emergency department visits and hospitalizations. This study highlights the substantial disease burden associated with cannabinoid hyperemesis syndrome in an online support group cohort and underscores the possible risks of heavy daily cannabis use and of use starting in adolescence. Future studies on heavy cannabis users are necessary to further elucidate cannabinoid hyperemesis syndrome and its link to daily cannabis use and the dangers of heavy use in adolescence., (Copyright © 2025 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Fontan patients exhibit decreased exercise capacity. However, there is a subset of high-performing Fontan (HPF) patients with excellent exercise capacity., Objectives: This study aims to: 1) create a Fontan-specific percent predicted peak VO 2 tool using exercise data; 2) examine clinical factors associated with HPF patients; and 3) examine late outcomes in HPF patients., Methods: Patients in the multi-institutional Fontan Outcomes Registry Using CMR Examination above the age of 8 years who had a maximal exercise test were included. An HPF patient was defined as a patient in the upper Fontan-specific percent predicted peak VO 2 quartile. Multivariable logistic regression was employed to investigate factors associated with the HPF and Cox regression was used to examine the association between HPF patients and late outcomes (composite of death or listing for cardiac transplant)., Results: The study included 813 patients (mean age: 20.2 ± 8.7 years). An HPF patient was associated with left ventricular morphology (OR: 1.50, P  = 0.04), mixed morphology (OR: 2.23, P  < 0.001), and a higher ejection fraction (OR: 1.31 for 10% increase, P  = 0.01). Patients with at least moderate atrioventricular valve regurgitation, protein-losing enteropathy, or who were using psychiatric medications, were less likely to be an HPF patient. After a mean follow-up of 3.7 years, 46 (5.7%) patients developed a composite endpoint. HPF had a lower risk of death or listing for cardiac transplant (HR: 0.06 [95% CI: 0.01-0.25])., Conclusions: Patients with HPF have more favorable outcomes when compared to patients with lower exercise capacity. This large registry data highlights the role of exercise testing in providing personalized care and surveillance post-Fontan., Competing Interests: The FORCE registry is funded through a grant from 10.13039/100020415Additional Ventures and Evan’s Heart. The project described was supported by the 10.13039/100000002National Institutes of Health through Grant Number UL1 TR001857, KL2 TR001856, and/or TL1 TR001858. Dr Rathod received research grant support from Mezzion Pharmaceuticals as the Global PI for the FUEL-2 trial which is a drug RCT in Fontan patients. Dr Alsaied is a center PI for the same trial and also receives similar grant support. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Background: Mandibular fractures account for up to 48.8% of pediatric facial fractures; however, there are a wide range of available treatment modalities, and few studies describe trends in adverse outcomes of these injuries. This study describes fracture cause, pattern, management, and treatment outcomes in pediatric mandibular fracture patients., Methods: A retrospective review was performed of patients younger than 18 years who were evaluated for mandibular fractures at a pediatric level I trauma center between 2006 and 2021. Variables studied included demographics, cause, medical history, associated facial fractures, other associated injuries, treatments, and outcomes., Results: A total of 530 pediatric patients with 829 mandibular fractures were included in the analysis. Most isolated mandibular fractures were treated with physical therapy and rest ( n = 253 [47.7%]). Patients with combination fractures, specifically those involving the parasymphysis and angle, were 2.63 times more likely to undergo surgical management compared with patients with a single facial fracture ( P < 0.0001). Older age ( P < 0.001), sex ( P = 0.042), mechanism ( P = 0.008) and cause of injury ( P = 0.002), and specific fractures (eg, isolated angle [ P = 0.001]) were more associated with adverse outcomes. The odds of adverse outcomes were higher for patients treated with closed reduction and external fixation or open reduction and internal fixation compared with conservative management (OR, 1.8, 95% CI, 1.0 to 3.2; and OR, 2.1, 95% CI, 1.2 to 3.5, respectively)., Conclusions: Fracture type, mechanism of injury, and treatment modality in pediatric mandibular fractures are associated with distinct rates and types of adverse outcomes. Large-scale studies characterizing these injuries are critical for guiding physicians in the management of these patients., Clinical Question/level of Evidence: Risk, III., (Copyright © 2023 by the American Society of Plastic Surgeons.)

Whole-genome sequencing (WGS) data is facilitating genome-wide identification of rare noncoding variants, while elucidating their roles in disease remains challenging. Towards this end, we first revisit a reported significant brain-related association signal of autism spectrum disorder (ASD) detected from de novo noncoding variants attributed to deep-learning and show that local GC content can capture similar association signals. We further show that the association signal appears driven by variants from male proband-female sibling pairs that are upstream of assigned genes. We then develop Expression Neighborhood Sequence Association Study (ENSAS), which utilizes gene expression correlations and sequence information, to more systematically identify phenotype-associated variant sets. Applying ENSAS to the same set of de novo variants, we identify gene expression-based neighborhoods showing significant ASD association signal, enriched for synapse-related gene ontology terms. For these top neighborhoods, we also identify chromatin states annotations of variants that are predictive of the proband-sibling local GC content differences. Our work provides new insights into associations of non-coding de novo mutations in ASD and presents an analytical framework applicable to other phenotypes., Competing Interests: Competing interests The authors declare no competing interests.