{"doi":"10.1101/2025.06.05.25329055","title":"An atlas of exposome-phenome associations in health and disease risk","abstract":"Non-genetic exposures including nutrients, lifestyle factors, consumables, and pollutants substantially contribute to phenotypic variation. Most studies assess only a few exposures or phenotypes, yielding fragmented exposome-phenome relationships. Systematic approaches are needed to quantify how the exposome the totality of environmental exposures relates broadly to clinically relevant phenotypes. We developed a resource benchmarking the role of the exposome using data from the National Health and Nutrition Examination Survey (NHANES), cataloging 619 exposures and 278 phenotypes, and systematically testing associations (Phenotype-exposure-wide association study [P-ExWAS]). Among 119k associations, 5% (n=5,661) were Bonferroni significant, and 40% replicated across independent population samples. Single exposures explained modest variance (median R-squared=0.5%; interquartile range [IQR]: 0.27 - 1.10%). Twenty simultaneous exposome factors increased median variance explained to 3.5% (IQR: 1.8 - 7.8%), comparable to 1M genetic variants. The exposome-phenome atlas is available at: http://apps.chiragjpgroup.org/pe_atlas/.","journal":null,"year":2025,"id":6135,"datarank":0.15495386640610476,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.050981789322112954,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.050981789322112954,"corpus_percentile":42.88039056143206,"corpus_rank":703,"citation_count":2,"citer_count":1,"citers_with_citation_signal":1,"citers_with_endowment":1,"datacite_reuse_total":0,"is_dataset":true,"is_dataset_confidence":0.6837,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-06-06","fair_score":38.3333,"fair_percentile":19.217238346525946,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":148,"name":"John P. A. Ioannidis","orcid":"0000-0003-3118-6859","position":1,"is_corresponding":false},{"id":2424,"name":"Arjun Kumar Manrai","orcid":"0000-0001-9657-9800","position":2,"is_corresponding":false},{"id":833,"name":"Chirag J. Patel","orcid":"0000-0002-8756-8525","position":0,"is_corresponding":true}],"reference_count":54,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-03-01T18:20:47.508186Z","pmid":"40661264","pmcid":"PMC12259201","fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":"green","license":"cc-by-nc","views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":52.5,"fair_a":55.0,"fair_i":12.5,"fair_r":33.3333,"fair_zscore":-0.6222,"fair_rationale":{"fair_score":38.33,"has_llm":true,"dimensions":{"F":{"name":"Findable","score":52.5,"criteria":[{"key":"f_has_doi","label":"Has a persistent DOI","kind":"deterministic","weight":1.0,"fraction":1.0,"signal":"DOI present","rationale":null},{"key":"f_repository_presence","label":"Indexed in repositories / literature DBs","kind":"deterministic","weight":1.0,"fraction":1.0,"signal":"datacite=0, pmcid=True, pmid=True","rationale":null},{"key":"f_persistent_ids","label":"Resolvable scholarly identifiers (OpenAlex)","kind":"deterministic","weight":0.5,"fraction":0.0,"signal":"no OpenAlex id","rationale":null},{"key":"f_metadata_richness","label":"Rich, machine-readable metadata","kind":"llm","weight":1.0,"fraction":0.25,"signal":null,"rationale":"The paper provides a DOI and basic citation metadata but lacks explicit machine-readable metadata such as structured schema.org annotations or formal metadata standards."}]},"A":{"name":"Accessible","score":55.0,"criteria":[{"key":"a_open_access","label":"Open Access / files deposited","kind":"deterministic","weight":1.5,"fraction":1.0,"signal":"Open Access","rationale":null},{"key":"a_retrievable","label":"Free full text retrievable","kind":"deterministic","weight":1.0,"fraction":0.0,"signal":"0 OA location(s)","rationale":null},{"key":"a_access_protocol","label":"Clear data/code access protocol","kind":"llm","weight":1.0,"fraction":0.5,"signal":null,"rationale":"The paper provides URLs for the atlas and code, but the protocol for accessing the underlying processed data is not fully clear, as the data must be obtained separately from NHANES."}]},"I":{"name":"Interoperable","score":12.5,"criteria":[{"key":"i_linked_data","label":"Linked datasets / DataCite relations","kind":"deterministic","weight":1.0,"fraction":0.0,"signal":"linked_datasets=0, datacite=0","rationale":null},{"key":"i_standard_ids","label":"References data via standard accessions","kind":"deterministic","weight":1.0,"fraction":0.0,"signal":"accessions=0, trials=0","rationale":null},{"key":"i_standards","label":"Standard formats, vocabularies & identifiers","kind":"llm","weight":1.0,"fraction":0.25,"signal":null,"rationale":"The paper does not mention use of standard vocabularies, ontologies, or data formats (e.g., CSV, JSON) for exposures and phenotypes, limiting interoperability."}]},"R":{"name":"Reusable","score":33.33,"criteria":[{"key":"r_license","label":"Clear, open reuse license","kind":"deterministic","weight":1.5,"fraction":0.0,"signal":"no license","rationale":null},{"key":"r_downloads","label":"Demonstrated reuse (downloads)","kind":"deterministic","weight":0.5,"fraction":0.0,"signal":"downloads=0","rationale":null},{"key":"r_version","label":"Versioned / maintained","kind":"deterministic","weight":0.5,"fraction":0.0,"signal":"no version chain","rationale":null},{"key":"r_dataset","label":"Classified as a data resource","kind":"deterministic","weight":0.5,"fraction":1.0,"signal":"is_dataset","rationale":null},{"key":"r_reusability","label":"Data-availability statement, license & reproducibility","kind":"llm","weight":2.0,"fraction":0.5,"signal":null,"rationale":"The paper includes a CC BY-NC license, provides code and an interactive atlas, but does not directly provide the processed data or a full reproducible environment, and the license restricts commercial reuse."}]}},"suggestions":["Add machine-readable metadata (e.g., schema.org/Dataset markup) to the atlas website and paper.","Provide a direct download link for the processed summary statistics in a standard format (e.g., CSV) with a data dictionary.","Use standard ontologies (e.g., ExO, NCIT) to annotate exposures and phenotypes for better interoperability.","Include a container (e.g., Docker) or detailed computational environment specification to enhance reproducibility.","Consider a more permissive license (e.g., CC BY) to allow broader reuse."],"model":"deepseek/deepseek-v4-flash","agent_version":"fair_agent_v1","fulltext_source":"epmc_xml"},"fair_model":"deepseek/deepseek-v4-flash","fair_agent_version":"fair_agent_v1","fair_fulltext_source":"epmc_xml","fair_has_llm":true,"fair_computed_at":"2026-06-17T23:00:33.454538Z","clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}