ArticleProceedings of the National Academy of Sciences of the United States of America2020
Multiomic blood correlates of genetic risk identify presymptomatic disease alterations.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
23 citing papers in PubMed.
- Review
- Early life adversity and risk for non-communicable health outcomes: challenges and opportunities for a maturing field.BMC medicine · 2025Review
- Placental network differences among obstetric syndromes identified with an integrated multiomics approach.Communications biology · 2025Article
- The Circulating Proteome─Technological Developments, Current Challenges, and Future Trends.Journal of proteome research · 2024Article
- The relationship between 11 different polygenic longevity scores, parental lifespan, and disease diagnosis in the UK Biobank.GeroScience · 2024Article
- A Multiomics, Molecular Atlas of Breast Cancer Survivors.Metabolites · 2024Article
- The transition from genomics to phenomics in personalized population health.Nature reviews. Genetics · 2024Review
- Cross-sectional network analysis of plasma proteins/metabolites correlated with pathogenesis and therapeutic response in acute promyelocytic leukemia.Frontiers of medicine · 2024Article
- Analytical challenges in omics research on asthma and allergy: A National Institute of Allergy and Infectious Diseases workshop.The Journal of allergy and clinical immunology · 2024Article
- A data-driven approach to improve wellness and reduce recurrence in cancer survivors.Frontiers in oncology · 2024Article
- Animal Wellness: The Power of Multiomics and Integrative Strategies: Multiomics in Improving Animal Health.Veterinary medicine international · 2024Review
- An epidemiological introduction to human metabolomic investigations.Trends in endocrinology and metabolism: TEM · 2023Review
- Cumulative Genetic Score andNeurology. Genetics · 2023Article
- Multiomic signatures of body mass index identify heterogeneous health phenotypes and responses to a lifestyle intervention.Nature medicine · 2023Article
- APOE ɛ4 allele and TOMM40-APOC1 variants jointly contribute to survival to older ages.Aging cell · 2022Article
- Distribution of 54 polygenic risk scores for common diseases in long lived individuals and their offspring.GeroScience · 2022Article
- Multi-omics reveals microbiome, host gene expression, and immune landscape in gastric carcinogenesis.iScience · 2022Article
- Blood-based biomarkers of inflammation in amyotrophic lateral sclerosis.Molecular neurodegeneration · 2022Review
- Artificial intelligence for precision medicine in autoimmune liver disease.Frontiers in immunology · 2022Review
- The Coaching for Cognition in Alzheimer's (COCOA) trial: Study design.Alzheimer's & dementia (New York, N. Y.) · 2022Article
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
Transitions from health to disease are characterized by dysregulation of biological networks under the influence of genetic and environmental factors, often over the course of years to decades before clinical symptoms appear. Understanding these dynamics has important implications for preventive medicine. However, progress has been hindered both by the difficulty of identifying individuals who will eventually go on to develop a particular disease and by the inaccessibility of most disease-relevant tissues in living individuals. Here we developed an alternative approach using polygenic risk scores (PRSs) based on genome-wide association studies (GWAS) for 54 diseases and complex traits coupled with multiomic profiling and found that these PRSs were associated with 766 detectable alterations in proteomic, metabolomic, and standard clinical laboratory measurements (clinical labs) from blood plasma across several thousand mostly healthy individuals. We recapitulated a variety of known relationships (e.g., glutamatergic neurotransmission and inflammation with depression, IL-33 with asthma) and found associations directly suggesting therapeutic strategies (e.g., Ω-6 supplementation and IL-13 inhibition for amyotrophic lateral sclerosis) and influences on longevity (leukemia inhibitory factor, ceramides). Analytes altered in high-genetic-risk individuals showed concordant changes in disease cases, supporting the notion that PRS-associated analytes represent presymptomatic disease alterations. Our results provide insights into the molecular pathophysiology of a range of traits and suggest avenues for the prevention of health-to-disease transitions.
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