Publications by authors named "David Crosslin"
Article Synopsis
- Current studies on electronic health records (EHR) using machine learning highlight the need for better patient representation to identify new medical patterns.
- A novel unsupervised method was developed to embed high-dimensional EHR data and successfully predicts disease events and assesses patient diversity in complex diseases.
- Validated on extensive datasets, the approach revealed distinct comorbidity patterns and variations in disease outcomes, demonstrating the effectiveness of representation learning in EHR analysis.
Article Synopsis
- Respiratory infections are a major global health issue, but the genetic factors influencing them are not well understood, leading to this study that aimed to investigate genetic determinants through genome-wide association studies (GWAS).
- The research analyzed data from 19,459 patients with respiratory infections and 101,438 controls in Stage 1, discovering 56 significant genetic signals, including one strong signal related to a gene important for immune response, but the follow-up Stage 2 study did not replicate these findings.
- Possible reasons for the lack of replication include variations in how the studies were conducted and differences in patient populations, but the research suggests a novel gene may be linked to susceptibility to respiratory infections, warranting further investigation.
Polygenic risk scores (PRSs) have improved in predictive performance, but several challenges remain to be addressed before PRSs can be implemented in the clinic, including reduced predictive performance of PRSs in diverse populations, and the interpretation and communication of genetic results to both providers and patients. To address these challenges, the National Human Genome Research Institute-funded Electronic Medical Records and Genomics (eMERGE) Network has developed a framework and pipeline for return of a PRS-based genome-informed risk assessment to 25,000 diverse adults and children as part of a clinical study. From an initial list of 23 conditions, ten were selected for implementation based on PRS performance, medical actionability and potential clinical utility, including cardiometabolic diseases and cancer.
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- Clostridioides difficile infection (CDI) is a major cause of diarrhea in hospitals across North America and Europe, leading to significant health risks.
- Previous risk factors don't fully explain why some people get CDI while others don't, suggesting a genetic component to susceptibility.
- A study involving nearly 20,000 participants found that variations in the DRB locus of the MHC (HLA) II region may increase the likelihood of developing CDI, indicating that genetic factors could influence how the body responds to this infection.
Article Synopsis
- Polygenic risk scores (PRS) can help identify individuals at higher risk for colorectal cancer (CRC), but current models based on European ancestry data don't perform well for non-European populations.
- A study expands PRS development by adding Asian ancestry data alongside European data, resulting in improved predictive accuracy across diverse racial and ethnic groups in the US.
- The findings emphasize the need for including more non-European ancestry populations to enhance risk prediction and ensure equitable clinical application of PRS in CRC prevention.
Background: Evolving ARDS epidemiology and management during COVID-19 have prompted calls to reexamine the construct validity of Berlin criteria, which have been rarely evaluated in real-world data. We developed a Berlin ARDS definition (EHR-Berlin) computable in electronic health records (EHR) to (1) assess its construct validity, and (2) assess how expanding its criteria affected validity.
Methods: We performed a retrospective cohort study at two tertiary care hospitals with one EHR, among adults hospitalized with COVID-19 February 2020-March 2021.
Article Synopsis
- - The text discusses the advancements in polygenic risk scores (PRS) and their potential to enhance clinical practice, but highlights challenges in effectiveness across diverse populations, which can worsen health disparities.
- - A project funded by NHGRI called the eMERGE Network is evaluating PRS for 23 health conditions in 25,000 individuals from different backgrounds, focusing on actionable findings and relevant evidence for African and Hispanic populations.
- - The study identified ten key health conditions for PRS assessment (like breast cancer and diabetes), and established a framework for implementing PRS in clinical settings, ensuring compliance and reliability across different genetic ancestries.
Article Synopsis
- The study addresses challenges in selecting computational phenotypes for research by proposing a novel metadata framework to improve retrieval and reuse of these phenotypes.
- Twenty active researchers contributed to identifying 39 relevant metadata elements, which were then evaluated through surveys and annotation tasks involving type-2 diabetes mellitus phenotypes.
- Results showed over 90% satisfaction with the framework's utility, highlighting effectiveness in phenotype description and validation, while noting challenges in data collection complexity and associated costs.
Article Synopsis
- Polygenic risk scores (PRS) can help target colorectal cancer (CRC) screening for those at higher risk, but current versions are less effective for non-European populations.
- Researchers combined data from Asian ancestry with European ancestry datasets to improve PRS accuracy, achieving better performance across different racial/ethnic groups.
- The study suggests that adding more non-European data, particularly from Black/African American and Latinx/Hispanic populations, is essential for enhancing risk prediction and promoting equitable clinical practices.
Article Synopsis
- The study aims to assess the risk of common diseases by considering clinical, monogenic, and polygenic factors, which may be reflected in an individual's family history.
- The eMERGE network is enrolling 25,000 individuals in a prospective study to create and return a comprehensive risk assessment report (GIRA) that includes various genetic risk factors and care recommendations.
- The GIRA report provides actionable guidelines for health care based on genetic data, highlighting the importance of integrating genetic risk assessment into routine health care practices.
Unlabelled: Vascular dysfunction and capillary leak are common in critically ill COVID-19 patients, but identification of endothelial pathways involved in COVID-19 pathogenesis has been limited. Angiopoietin-like 4 (ANGPTL4) is a protein secreted in response to hypoxic and nutrient-poor conditions that has a variety of biological effects including vascular injury and capillary leak.
Objectives: To assess the role of ANGPTL4 in COVID-19-related outcomes.
Objective: High BMI is associated with many comorbidities and mortality. This study aimed to elucidate the overall clinical risk of obesity using a genome- and phenome-wide approach.
Methods: This study performed a phenome-wide association study of BMI using a clinical cohort of 736,726 adults.
Article Synopsis
- Immunoglobulin A (IgA) plays a crucial role in immune response to food and pathogens and is linked to various conditions like celiac disease and inflammatory bowel disease.
- A genome-wide association study examined blood IgA levels in over 41,000 people, identifying 20 key genetic loci that affect IgA levels, including novel genes.
- Findings suggest genetic factors influencing IgA can impact diseases such as IgA nephropathy and type 2 diabetes, with African ancestry showing higher IgA levels and more IgA-increasing genetic variants.
Significance Statement: Pathogenic structural genetic variants, also known as genomic disorders, have been associated with pediatric CKD. This study extends those results across the lifespan, with genomic disorders enriched in both pediatric and adult patients compared with controls. In the Chronic Renal Insufficiency Cohort study, genomic disorders were also associated with lower serum Mg, lower educational performance, and a higher risk of death.
View Article and Find Full Text PDFChronic kidney disease (CKD) is a common complex condition associated with high morbidity and mortality. Polygenic prediction could enhance CKD screening and prevention; however, this approach has not been optimized for ancestrally diverse populations. By combining APOL1 risk genotypes with genome-wide association studies (GWAS) of kidney function, we designed, optimized and validated a genome-wide polygenic score (GPS) for CKD.
View Article and Find Full Text PDFIntegrating data across heterogeneous research environments is a key challenge in multi-site, collaborative research projects. While it is important to allow for natural variation in data collection protocols across research sites, it is also important to achieve interoperability between datasets in order to reap the full benefits of collaborative work. However, there are few standards to guide the data coordination process from project conception to completion.
View Article and Find Full Text PDFClinical and epidemiological studies have shown that circulatory system diseases and nervous system disorders often co-occur in patients. However, genetic susceptibility factors shared between these disease categories remain largely unknown. Here, we characterized pleiotropy across 107 circulatory system and 40 nervous system traits using an ensemble of methods in the eMERGE Network and UK Biobank.
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- * Researchers conducted a phenome-wide association study using health data from three cohorts to identify the relationship between hereditary cancer genes and associated phenotypes.
- * Among 214,020 participants, they confirmed all 38 known gene-cancer associations and discovered 19 new associations, particularly linking seven of them to neoplasms (tumors).
Uterine fibroids (UF) are common pelvic tumors in women, heritable, and genome-wide association studies (GWAS) have identified ~ 30 loci associated with increased risk in UF. Using summary statistics from a previously published UF GWAS performed in a non-Hispanic European Ancestry (NHW) female subset from the Electronic Medical Records and Genomics (eMERGE) Network, we constructed a polygenic risk score (PRS) for UF. UF-PRS was developed using PRSice and optimized in the separate clinical population of BioVU.
View Article and Find Full Text PDFPurpose: The goal of Electronic Medical Records and Genomics (eMERGE) Phase III Network was to return actionable sequence variants to 25,084 consenting participants from 10 different health care institutions across the United States. The purpose of this study was to evaluate system-based issues relating to the return of results (RoR) disclosure process for clinical grade research genomic tests to eMERGE3 participants.
Methods: RoR processes were developed and approved by each eMERGE institution's internal review board.
Background: Unbiased estimates of penetrance are challenging but critically important to make informed choices about strategies for risk management through increased surveillance and risk-reducing interventions.
Methods: We studied the penetrance and clinical outcomes of 7 breast cancer susceptibility genes (, , , , , , and ) in almost 13 458 participants unselected for personal or family history of breast cancer. We identified 242 female participants with pathogenic or likely pathogenic variants in 1 of the 7 genes for penetrance analyses, and 147 women did not previously know their genetic results.
Background: Genetic variants in complement genes have been associated with a wide range of human disease states, but well-powered genetic association studies of complement activation have not been performed in large multiethnic cohorts.
Methods: We performed medical records-based genome-wide and phenome-wide association studies for plasma C3 and C4 levels among participants of the Electronic Medical Records and Genomics (eMERGE) network.
Results: In a GWAS for C3 levels in 3949 individuals, we detected two genome-wide significant loci: chr.