Genomic data in the All of Us Research Program

Nature, Journal Year: 2024, Volume and Issue: 627(8003), P. 340 - 346

Published: Feb. 19, 2024

Abstract Comprehensively mapping the genetic basis of human disease across diverse individuals is a long-standing goal for field genetics 1–4 . The All Us Research Program longitudinal cohort study aiming to enrol group at least one million USA accelerate biomedical research and improve health 5,6 Here we describe programme’s genomics data release 245,388 clinical-grade genome sequences. This resource unique in its diversity as 77% participants are from communities that historically under-represented 46% racial ethnic minorities. identified more than 1 billion variants, including 275 previously unreported 3.9 which had coding consequences. Leveraging linkage between genomic electronic record, evaluated 3,724 variants associated with 117 diseases found high replication rates both European ancestry African ancestry. Summary-level publicly available, individual-level can be accessed by researchers through Researcher Workbench using passport model median time initial researcher registration access 29 hours. We anticipate this dataset will advance promise medicine all.

Language: Английский

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Bias in artificial intelligence algorithms and recommendations for mitigation

PLOS Digital Health, Journal Year: 2023, Volume and Issue: 2(6), P. e0000278 - e0000278

Published: June 22, 2023

The adoption of artificial intelligence (AI) algorithms is rapidly increasing in healthcare. Such may be shaped by various factors such as social determinants health that can influence outcomes. While AI have been proposed a tool to expand the reach quality healthcare underserved communities and improve equity, recent literature has raised concerns about propagation biases disparities through implementation these algorithms. Thus, it critical understand sources bias inherent AI-based This review aims highlight potential within each step developing healthcare, starting from framing problem, data collection, preprocessing, development, validation, well their full implementation. For steps, we also discuss strategies mitigate disparities. A checklist was developed with recommendations for reducing during development stages. It important developers users keep considerations mind advance equity all populations.

Language: Английский

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New insights from the last decade of research in psychiatric genetics: discoveries, challenges and clinical implications

World Psychiatry, Journal Year: 2023, Volume and Issue: 22(1), P. 4 - 24

Published: Jan. 14, 2023

Psychiatric genetics has made substantial progress in the last decade, providing new insights into genetic etiology of psychiatric disorders, and paving way for precision psychiatry, which individual profiles may be used to personalize risk assessment inform clinical decision‐making. Long recognized heritable, recent evidence shows that disorders are influenced by thousands variants acting together. Most these commonly occurring, meaning every a each disorder, from low high. A series large‐scale studies have discovered an increasing number common rare robustly associated with major disorders. The most convincing biological interpretation findings implicates altered synaptic function autism spectrum disorder schizophrenia. However, mechanistic understanding is still incomplete. In line their extensive epidemiological overlap, appear exist on continua share large degree one another. This provides further support notion current diagnoses do not represent distinct pathogenic entities, ongoing attempts reconceptualize nosology. also influences range behavioral somatic traits diseases, including brain structures, cognitive function, immunological phenotypes cardiovascular disease, suggesting shared potential importance. Current polygenic score tools, predict susceptibility illness, yet provide clinically actionable information. likely improve coming years, they eventually become part practice, stressing need educate clinicians patients about use misuse. review discusses key possible applications, suggests future directions.

Language: Английский

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Association of step counts over time with the risk of chronic disease in the All of Us Research Program

Nature Medicine, Journal Year: 2022, Volume and Issue: 28(11), P. 2301 - 2308

Published: Oct. 10, 2022

The association between physical activity and human disease has not been examined using commercial devices linked to electronic health records. Using the records data from All of Us Research Program, we show that step count volumes as captured by participants' own Fitbit were associated with risk chronic across entire phenome. Of 6,042 participants included in study, 73% female, 84% white 71% had a college degree, median age 56.7 (interquartile range 41.5-67.6) years body mass index 28.1 (24.3-32.9) kg m-2. Participants walked 7,731.3 (5,866.8-9,826.8) steps per day over monitoring period 4.0 (2.2-5.6) total 5.9 million person-days monitoring. relationship incident was inverse linear for obesity (n = 368), sleep apnea 348), gastroesophageal reflux 432) major depressive disorder 467), values above 8,200 daily protection disease. relationships diabetes 156) hypertension 482) nonlinear no further reduction 8,000-9,000 steps. Although validation more diverse sample is needed, these findings provide real-world evidence-base clinical guidance regarding levels are necessary reduce risk.

Language: Английский

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Pharmacogenomics: Driving Personalized Medicine

Pharmacological Reviews, Journal Year: 2023, Volume and Issue: 75(4), P. 789 - 814

Published: March 16, 2023

Abstract

Personalized medicine tailors therapies, disease prevention, and health maintenance to the individual, with pharmacogenomics serving as a key tool improve outcomes prevent adverse effects. Advances in genomics have transformed pharmacogenetics, traditionally focused on single gene-drug pairs, into pharmacogenomics, encompassing all "-omics" fields (e.g., proteomics, transcriptomics, metabolomics, metagenomics). This review summarizes basic principles relevant translation assessing pharmacogenomics' central role converging diverse elements of personalized medicine. We discuss genetic variations pharmacogenes (drug-metabolizing enzymes, drug transporters, receptors), their clinical relevance biomarkers, legacy decades research pharmacogenetics. All types including proteins, nucleic acids, viruses, cells, genes, irradiation, can benefit from genomics, expanding across Food Drug Administration approvals therapeutics involving biomarkers increase rapidly, demonstrating growing impact pharmacogenomics. A beacon for therapeutic approaches, molecularly targeted cancer therapies highlight trends discovery applications. To account human complexity, multicomponent biomarker panels genetic, personal, environmental factors guide diagnosis increasingly artificial intelligence cope extreme data complexities. However, application encounters substantial hurdles, such unknown validity ethnic groups, underlying bias care, real-world validation. address science technologies germane medicine, integrated economic, ethical, regulatory issues, providing insights current status future direction care.

Significance Statement

aims optimize care individual patients use predictive Pharmacogenomics drives guides development therapeutics. addresses large-scale repositories accelerating medical advances. The is discussed, along hurdles impeding broad implementation, context ethics, economics, affairs.

Language: Английский

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Causal effects on complex traits are similar for common variants across segments of different continental ancestries within admixed individuals

Nature Genetics, Journal Year: 2023, Volume and Issue: 55(4), P. 549 - 558

Published: March 20, 2023

Language: Английский

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Glucagon-like Peptide-1 Receptor Agonists Associated Gastrointestinal Adverse Events: A Cross-Sectional Analysis of the National Institutes of Health All of Us Cohort

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(2), P. 199 - 199

Published: Feb. 2, 2024

Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are commonly used diabetes and obesity medications but have been associated with gastrointestinal (GI) adverse events. However, real-world evidence on comparative GI reaction profiles is limited. Objectives: This study aimed to evaluate events among GLP-1 RA users compare semaglutide, dulaglutide, liraglutide, exenatide safety regarding the profile. Methods: retrospective cross-sectional analysis utilized data 10,328 adults diabetes/obesity in National Institutes of Health All Us cohort. New were identified, examined. Logistic regression determined factors Results: The mean age population was 61.4 ± 12.6 years, 65.7% female, 51.3% White, they had a high comorbidity burden. Abdominal pain (57.6%) most common event, followed by constipation (30.4%), diarrhea (32.7%), nausea vomiting (23.4%), bleeding (15.9%), gastroparesis (5.1%), pancreatitis (3.4%). Dulaglutide liraglutide higher rates abdominal pain, constipation, diarrhea, than semaglutide exenatide. Liraglutide highest (4.0% 3.8%, respectively). Compared dulaglutide odds vomiting. They also semaglutide. No significant differences existed or risks between RAs. Conclusions: In this cohort, Differences agents, appearing safer other RAs, except for gastroparesis. These findings can inform selection considering risk factors. Further studies needed causal relationship concomitant medication use.

Language: Английский

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The frequency of pathogenic variation in the All of Us cohort reveals ancestry-driven disparities

Communications Biology, Journal Year: 2024, Volume and Issue: 7(1)

Published: Feb. 19, 2024

Abstract Disparities in data underlying clinical genomic interpretation is an acknowledged problem, but there a paucity of demonstrating it. The All Us Research Program collecting including whole-genome sequences, health records, and surveys for at least million participants with diverse ancestry access to healthcare, representing one the largest biomedical research repositories its kind. Here, we examine pathogenic likely variants that were identified cohort. European subgroup showed highest overall rate variation, 2.26% having variant. Other groups had lower rates 1.62% African group 1.32% Latino/Admixed American group. Pathogenic most frequently observed genes related Breast/Ovarian Cancer or Hypercholesterolemia. Variant frequencies many consistent from public gnomAD database, some notable exceptions resolved using subsets. Differences variant frequency between ancestral generally indicate biases ascertainment knowledge about those variants, deviations may be indicative differences disease prevalence. This work will allow targeted precision medicine efforts revealed disparities.

Language: Английский

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Impact of population screening for Lynch syndrome insights from the All of Us data

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 9, 2025

Language: Английский

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Bias recognition and mitigation strategies in artificial intelligence healthcare applications

npj Digital Medicine, Journal Year: 2025, Volume and Issue: 8(1)

Published: March 11, 2025

Artificial intelligence (AI) is delivering value across all aspects of clinical practice. However, bias may exacerbate healthcare disparities. This review examines the origins in AI, strategies for mitigation, and responsibilities relevant stakeholders towards achieving fair equitable use. We highlight importance systematically identifying engaging mitigation activities throughout AI model lifecycle, from conception through to deployment longitudinal surveillance.

Language: Английский

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