{"doi":"10.1038/s41586-024-07708-2","title":"Sources of gene expression variation in a globally diverse human cohort","abstract":"Abstract Genetic variation that influences gene expression and splicing is a key source of phenotypic diversity 1–5 . Although invaluable, studies investigating these links in humans have been strongly biased towards participants of European ancestries, which constrains generalizability and hinders evolutionary research. Here to address these limitations, we developed MAGE, an open-access RNA sequencing dataset of lymphoblastoid cell lines from 731 individuals from the 1000 Genomes Project 6 , spread across 5 continental groups and 26 populations. Most variation in gene expression (92%) and splicing (95%) was distributed within versus between populations, which mirrored the variation in DNA sequence. We mapped associations between genetic variants and expression and splicing of nearby genes ( cis -expression quantitative trait loci (eQTLs) and cis -splicing QTLs (sQTLs), respectively). We identified more than 15,000 putatively causal eQTLs and more than 16,000 putatively causal sQTLs that are enriched for relevant epigenomic signatures. These include 1,310 eQTLs and 1,657 sQTLs that are largely private to underrepresented populations. Our data further indicate that the magnitude and direction of causal eQTL effects are highly consistent across populations. Moreover, the apparent ‘population-specific’ effects observed in previous studies were largely driven by low resolution or additional independent eQTLs of the same genes that were not detected. Together, our study expands our understanding of human gene expression diversity and provides an inclusive resource for studying the evolution and function of human genomes.","journal":"Nature","year":2024,"id":417356,"datarank":1.4987820992601222,"base_score":4.290459441148391,"endowment":4.290459441148391,"self_citation_contribution":0.6435689161722588,"citation_network_contribution":0.8552131830878635,"self_endowment_contribution":0.6435689161722588,"citer_contribution":0.8552131830878635,"corpus_percentile":86.15301307341224,"corpus_rank":1791,"citation_count":72,"citer_count":69,"citers_with_citation_signal":43,"citers_with_endowment":43,"datacite_reuse_total":0,"is_dataset":true,"is_dataset_confidence":0.7655,"is_data_producer":true,"deposit_databanks":{"SRA":["PRJNA851328"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":70.8333,"fair_percentile":91.99021705900336,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":244011,"name":"Surya B. Chhetri","orcid":null,"position":1,"is_corresponding":false},{"id":51365,"name":"Michael G. Tassia","orcid":"0000-0002-5485-8155","position":2,"is_corresponding":false},{"id":51328,"name":"Arjun Biddanda","orcid":"0000-0003-1861-1523","position":3,"is_corresponding":false},{"id":49042,"name":"Stephanie M. Yan","orcid":"0000-0002-6880-465X","position":4,"is_corresponding":false},{"id":247496,"name":"Genevieve L. Wojcik","orcid":"0000-0001-7206-8088","position":5,"is_corresponding":false},{"id":103605,"name":"Alexis Battle","orcid":"0000-0002-5287-627X","position":6,"is_corresponding":false},{"id":49046,"name":"Rajiv C. McCoy","orcid":"0000-0003-0615-146X","position":7,"is_corresponding":false},{"id":53912,"name":"Dylan J. Taylor","orcid":"0000-0001-5806-4494","position":0,"is_corresponding":true}],"reference_count":72,"raw_metadata":null,"created_at":"2026-07-19T01:56:50.743370Z","pmid":"39020179","pmcid":"PMC11291278","fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":61.1111,"fair_a":75.0,"fair_i":60.0,"fair_r":33.3333,"fair_zscore":1.4401,"fair_rationale":{"fair_score":70.83,"has_llm":true,"taxonomy_version":"fair_taxonomy_v5","dimensions":{"F":{"name":"Findable","score":61.11,"criteria":[{"key":"f_dataset_pid","label":"Persistent identifier for the data","kind":"llm","weight":2.0,"fraction":1.0,"verdict":"yes","evidence":"https://doi.org/10.5281/zenodo.10535719","grounded":true,"rationale":"The paper provides a DOI for the processed data, which is a persistent identifier scheme.","anchors":["RDA-F1-01D — FAIR Data Maturity Model: 'Data is identified by a persistent identifier' (priorit","RDA-F1-02D — FAIR Data Maturity Model: 'Data is identified by a globally unique identifier'","FsF-F1-02D — F-UJI/FAIRsFAIR: 'Data is assigned a persistent identifier'"],"scored":true,"signal":null},{"key":"f_repository_named","label":"Named repository","kind":"llm","weight":2.0,"fraction":1.0,"verdict":"yes","evidence":"Newly generated RNA-seq data for the 731 individuals (779 total libraries) are available from the Sequence Read Archive (accession: PRJNA851328)","grounded":true,"rationale":"The paper names the Sequence Read Archive (SRA) as a repository, which is a curated archive listed in re3data/FAIRsharing.","anchors":["RDA-F4-01M — FAIR Data Maturity Model: metadata is offered so it can be harvested and indexed (","NIH DMS Policy Element 4 (NOT-OD-21-014) — name the repository where data will be archived","NSTC Desirable Characteristics of Data Repositories (2022) — 'Long-Term Sustainability', 'Reten"],"scored":true,"signal":null},{"key":"f_data_availability_statement","label":"Data-availability statement","kind":"llm","weight":2.0,"fraction":0.5,"verdict":"partial","evidence":"Newly generated RNA-seq data for the 731 individuals (779 total libraries) are available from the Sequence Read Archive (accession: PRJNA851328). Processed gene expression matrices and QTL mapping results are available from Zenodo (https://doi.org/10.5281/zenodo.10535719).","grounded":false,"rationale":"The statement points to repository records with accessions (Colavizza category 3). [downgraded to 'partial' — no verifiable quote from the paper] [majority verdict 'partial' (2/4 passes agreed)]","anchors":["Colavizza, Hrynaszkiewicz, Staden, Whitaker & McGillivray (2020), 'The citation advantage of li","Springer Nature research data policy — Data Availability Statements: standard statement templat","RDA-F3-01M — metadata clearly and explicitly includes the identifier of the data it describes"],"scored":false,"signal":null},{"key":"f_discovery_metadata","label":"Description of the dataset as an object","kind":"llm","weight":2.0,"fraction":0.0,"verdict":"no","evidence":"We performed RNA-seq of LCLs from 731 individuals from the 1000 Genomes Project6 (1KGP), which represented 26 globally distributed populations (27–30 individuals per population) across 5 continental groups.","grounded":false,"rationale":"The dataset content is described in running prose (sample size, populations) but there is no itemised inventory of files or variables. [downgraded to 'no' — no verifiable quote from the paper] [majority verdict 'no' (3/4 passes agreed)]","anchors":["RDA-F2-01M — 'Rich metadata is provided to allow discovery' (priority Essential)","FsF-F2-01M — F-UJI: 'Metadata includes descriptive core elements to support data findability'","FsF-R1-01MD — F-UJI: 'Metadata specifies the content of the data'"],"scored":false,"signal":null},{"key":"f_dataset_cited","label":"Dataset formally cited","kind":"llm","weight":1.0,"fraction":0.5,"verdict":"partial","evidence":"Newly generated RNA-seq data for the 731 individuals (779 total libraries) are available from the Sequence Read Archive (accession: PRJNA851328).","grounded":true,"rationale":"The dataset identifier appears only in the body text (data availability statement), not in the reference list. [majority verdict 'partial' (2/4 passes agreed)]","anchors":["FORCE11 Joint Declaration of Data Citation Principles (2014) — data should be cited as a first-","RDA-F3-01M — metadata clearly and explicitly includes the identifier of the data it describes","FsF-F3-01M — F-UJI: 'Metadata includes the identifier of the data it describes'"],"scored":true,"signal":null}]},"A":{"name":"Accessible","score":75.0,"criteria":[{"key":"a_data_openly_accessible","label":"Access route free of preconditions","kind":"llm","weight":2.0,"fraction":1.0,"verdict":"yes","evidence":"Newly generated RNA-seq data for the 731 individuals (779 total libraries) are available from the Sequence Read Archive (accession: PRJNA851328). Processed gene expression matrices and QTL mapping results are available from Zenodo (https://doi.org/10.5281/zenodo.10535719)","grounded":true,"rationale":"The data availability statement gives direct repository access with no precondition, and the abstract calls it 'open-access'. [majority verdict 'yes' (3/4 passes agreed)]","anchors":["RDA-A1.1-01D — 'Data is accessible through a free access protocol'","FsF-A1-01M — F-UJI: 'Metadata contains access level and access conditions of the data'","NSTC Desirable Characteristics of Data Repositories (2022) — 'Free and Easy Access'"],"scored":true,"signal":null},{"key":"a_access_conditions_stated","label":"Access level labelled","kind":"llm","weight":1.0,"fraction":1.0,"verdict":"yes","evidence":"we developed MAGE, an open-access RNA sequencing dataset","grounded":true,"rationale":"The paper explicitly labels the MAGE dataset as 'open-access' in the abstract, which is a standard access-level label. [majority verdict 'yes' (3/4 passes agreed)]","anchors":["FsF-A1-01M — F-UJI: 'Metadata contains access level and access conditions of the data'","RDA-A1-01M — metadata contains information to enable the user to get access to the data","COAR Controlled Vocabularies — Access Rights v1.0 (open / embargoed / restricted / metadata-onl"],"scored":false,"signal":null},{"key":"a_controlled_access_for_sensitive","label":"Gatekeeper for sensitive data","kind":"llm","weight":0.5,"fraction":0.0,"verdict":"no","evidence":null,"grounded":false,"rationale":"The data are from human subjects but are openly accessible with no gatekeeper named; the paper states the work was deemed not human subjects research and access is open.","anchors":["NIH Genomic Data Sharing Policy (NOT-OD-14-124) — controlled-access via a Data Access Committee","RDA-A1.2-01D — 'Data is accessible through an access protocol that supports authentication and ","NIH DMS Policy Element 5 (NOT-OD-21-014) — Access, Distribution, or Reuse Considerations (conse"],"scored":false,"signal":null},{"key":"a_timeline_retention","label":"Availability timing & retention","kind":"llm","weight":0.5,"fraction":0.0,"verdict":"no","evidence":null,"grounded":false,"rationale":"No sentence in the paper states how long the data will be retained or when they become available beyond the current publication. [majority verdict 'no' (2/4 passes agreed)]","anchors":["NIH DMS Plan Element 4 (NOT-OD-21-014) — Data Preservation, Access, and Associated Timelines","NSTC Desirable Characteristics (2022), Organizational Infrastructure: 'Retention Policy'","RDA-A2-01M — 'Metadata is guaranteed to remain available after data is no longer available'"],"scored":false,"signal":null}]},"I":{"name":"Interoperable","score":60.0,"criteria":[{"key":"i_open_nonproprietary_format","label":"Open file format","kind":"llm","weight":1.0,"fraction":0.0,"verdict":"no","evidence":null,"grounded":false,"rationale":"No file format is named for the released data; the raw data are in SRA (format not specified) and processed matrices are not described by format.","anchors":["FsF-R1.3-02D — F-UJI: 'Data is available in a file format recommended by the target research co","RDA-R1.3-02D — data is expressed in a machine-understandable community standard","RDA-I1-01D — data uses a knowledge representation expressed in a standardised format"],"scored":true,"signal":null},{"key":"i_community_standard_vocabulary","label":"Community standard / vocabulary","kind":"llm","weight":1.0,"fraction":1.0,"verdict":"yes","evidence":"We quantified gene expression levels using gene annotations from GENCODE (v.38)","grounded":true,"rationale":"GENCODE is a community-standard gene annotation resource, i.e., a data standard. [majority verdict 'yes' (3/4 passes agreed)]","anchors":["RDA-R1.3-01M — 'Metadata complies with a community standard' (priority Essential)","RDA-R1.3-01D — 'Data complies with a community standard'","RDA-I2-01M — '(Meta)data use vocabularies that follow FAIR principles'"],"scored":false,"signal":null},{"key":"i_qualified_references","label":"Identifiers for the resources the data depend on","kind":"llm","weight":0.5,"fraction":1.0,"verdict":"yes","evidence":"Compared with GTEx (dbGaP accession: phs000424.v9.p2)","grounded":true,"rationale":"The paper provides a qualified reference to an external dataset (GTEx) via its dbGaP accession.","anchors":["RDA-I3-01M — '(meta)data include references to other (meta)data'","RDA-I3-03M — 'metadata includes qualified references to other metadata'","FsF-I3-01M — F-UJI: 'Metadata includes links between the data and its related entities'"],"scored":false,"signal":null}]},"R":{"name":"Reusable","score":33.33,"criteria":[{"key":"r_reuse_license","label":"Reuse licence","kind":"llm","weight":2.0,"fraction":0.0,"verdict":"no","evidence":null,"grounded":false,"rationale":"No licence for the data is stated; the CC BY 4.0 licence applies only to the article text, not the dataset.","anchors":["RDA-R1.1-01M — 'Metadata includes information about the licence under which the data can be reu","RDA-R1.1-02M — 'Metadata refers to a standard reuse licence'","RDA-R1.1-03M — 'Metadata refers to a machine-understandable reuse licence'"],"scored":true,"signal":null},{"key":"r_provenance_methods","label":"Provenance of the data","kind":"llm","weight":1.0,"fraction":0.0,"verdict":"no","evidence":null,"grounded":false,"rationale":"The paper does not name the specific sequencing instrument, platform, or kit used to generate the RNA-seq data; only software tools are named for analysis. [majority verdict 'no' (2/4 passes agreed)]","anchors":["RDA-R1.2-01M — 'Metadata includes provenance information according to community- specific standa","FsF-R1.2-01M — F-UJI: 'Metadata includes provenance information about data creation or generati","W3C PROV-O (W3C Recommendation, 2013) — the entity/activity/agent model of provenance"],"scored":false,"signal":null},{"key":"r_documentation_codebook","label":"Documentation / codebook","kind":"llm","weight":1.0,"fraction":0.0,"verdict":"no","evidence":null,"grounded":false,"rationale":"No README, data dictionary, or codebook is named as accompanying the data; variable definitions are not provided inside the article either.","anchors":["RDA-R1-01M — '(Meta)data are richly described with a plurality of accurate and relevant attribu","FsF-R1-01MD — F-UJI: 'Metadata specifies the content of the data'","NIH DMS Policy Element 3 (NOT-OD-21-014) — Standards (documentation and metadata to accompany t"],"scored":false,"signal":null},{"key":"r_versioning","label":"Snapshot identified","kind":"llm","weight":0.5,"fraction":1.0,"verdict":"yes","evidence":"MAGE: Multi-ancestry Analysis of Gene Expression v1.0","grounded":true,"rationale":"The dataset is referred to with a version token 'v1.0' in the reference-list entry.","anchors":["DataCite Metadata Schema 4.6 — the 'Version' property","RDA-R1.2-01M — provenance information (which version was used is provenance)","NSTC Desirable Characteristics of Data Repositories (2022) — 'Provenance', 'Retention Policy'"],"scored":true,"signal":null},{"key":"x_code_availability","label":"Analysis code available","kind":"llm","weight":1.0,"fraction":1.0,"verdict":"yes","evidence":"available on GitHub (https://github.com/mccoy-lab/MAGE) and archived on Zenodo (https://doi.org/10.5281/zenodo.10072080)","grounded":true,"rationale":"The paper gives both a code repository URL and an archive DOI for the code, which are machine-resolvable locators.","anchors":["NIH DMS Policy Element 2 (NOT-OD-21-014) — 'Related Tools, Software and/or Code'","FAIR4RS Principles v1.0 (Chue Hong et al., 2022; RDA/FORCE11/ReSA) — FAIR Principles for Resear","FORCE11 Software Citation Principles (Smith, Katz & Niemeyer, 2016, PeerJ CS 2:e86)"],"scored":true,"signal":null},{"key":"x_funding_attribution","label":"Funder and award number","kind":"llm","weight":0.5,"fraction":1.0,"verdict":"yes","evidence":"R35GM133747","grounded":true,"rationale":"A specific NIH grant number (R35GM133747) is listed in the Acknowledgements.","anchors":["DataCite Metadata Schema 4.6 — 'FundingReference' property (funderName, funderIdentifier, award","Crossref Funder Registry — canonical funder identifiers for funding metadata","RDA-F2-01M — rich metadata provided to allow discovery (funding is part of the descriptive reco"],"scored":true,"signal":null}]}},"actions":[{"key":"r_reuse_license","dimension":"R","label":"Reuse licence","action":"Attach a standard, machine-readable open licence to the deposit — CC0 or CC BY, which is what Horizon Europe and most funders expect — and print the licence identifier in the paper. 'Free to use' is not a licence: it grants nothing a reuser's institution can rely on.","anchors":["yes","partial","no"],"verdict":"no","current":0.0,"evidence":null,"why":"No licence for the data is stated; the CC BY 4.0 licence applies only to the article text, not the dataset.","gain":16.67,"priority":"essential","scored":true},{"key":"i_open_nonproprietary_format","dimension":"I","label":"Open file format","action":"Release the data in an open, community-standard format (CSV/TSV, JSON, HDF5, NetCDF, FASTQ, VCF, NIfTI…) instead of — or alongside — any proprietary or instrument-native format, and name the format in the paper. A dataset that needs a €2,000 licence to open is not reusable.","anchors":["yes","partial","no"],"verdict":"no","current":0.0,"evidence":null,"why":"No file format is named for the released data; the raw data are in SRA (format not specified) and processed matrices are not described by format.","gain":8.33,"priority":"important","scored":true},{"key":"f_dataset_cited","dimension":"F","label":"Dataset formally cited","action":"Cite the dataset in the reference list like a publication — creator, year, title, repository, DOI/accession — and cite it in-text where it is used. Only a reference- list entry is machine-readable to Crossref/DataCite, and only a citation lets the data earn credit. Cite the clinical / human-subjects repository accession (e.g. from dbGaP or the European Genome-phenome Archive (EGA)) in the reference list.","anchors":["yes","partial","no"],"verdict":"partial","current":0.5,"evidence":"Newly generated RNA-seq data for the 731 individuals (779 total libraries) are available from the Sequence Read Archive (accession: PRJNA851328).","why":"The dataset identifier appears only in the body text (data availability statement), not in the reference list. [majority verdict 'partial' (2/4 passes agreed)]","gain":4.17,"priority":"important","scored":true},{"key":"f_data_availability_statement","dimension":"F","label":"Data-availability statement","action":"Replace the statement with the repository template: name the repository and give the accession or DOI (Colavizza category 3). This is the only DAS class associated with a measured citation advantage; 'available on reasonable request' and 'within the article' are not.","anchors":["yes","partial","no"],"verdict":"partial","current":0.5,"evidence":"Newly generated RNA-seq data for the 731 individuals (779 total libraries) are available from the Sequence Read Archive (accession: PRJNA851328). Processed gene expression matrices and QTL mapping results are available from Zenodo (https://doi.org/10.5281/zenodo.10535719).","why":"The statement points to repository records with accessions (Colavizza category 3). [downgraded to 'partial' — no verifiable quote from the paper] [majority verdict 'partial' (2/4 passes agreed)]","gain":0.0,"priority":"essential","scored":false},{"key":"f_discovery_metadata","dimension":"F","label":"Description of the dataset as an object","action":"Add a 'Data Records' section: itemise every file in the deposit and every variable or sample it holds, with counts and units. Describe the dataset as an object in its own right, not as a by-product of the findings — this is what makes it discoverable to someone who is not looking for your paper.","anchors":["yes","partial","no"],"verdict":"no","current":0.0,"evidence":"We performed RNA-seq of LCLs from 731 individuals from the 1000 Genomes Project6 (1KGP), which represented 26 globally distributed populations (27–30 individuals per population) across 5 continental groups.","why":"The dataset content is described in running prose (sample size, populations) but there is no itemised inventory of files or variables. [downgraded to 'no' — no verifiable quote from the paper] [majority verdict 'no' (3/4 passes agreed)]","gain":0.0,"priority":"essential","scored":false},{"key":"r_provenance_methods","dimension":"R","label":"Provenance of the data","action":"Name the instruments, kits, and software — with versions — that produced the data, not just the verbs. 'Reads were aligned' is not provenance; 'aligned with STAR v2.7.9a to GRCh38' is, because someone else can rerun it.","anchors":["yes","partial","no"],"verdict":"no","current":0.0,"evidence":null,"why":"The paper does not name the specific sequencing instrument, platform, or kit used to generate the RNA-seq data; only software tools are named for analysis. [majority verdict 'no' (2/4 passes agreed)]","gain":0.0,"priority":"important","scored":false},{"key":"r_documentation_codebook","dimension":"R","label":"Documentation / codebook","action":"Ship a README and a data dictionary IN the deposit — every file, every variable, its units, its allowed values, its missing-value codes. It is the cheapest single thing that makes a dataset usable by someone who was not in the lab, and a table buried in the article does not travel with the data.","anchors":["yes","partial","no"],"verdict":"no","current":0.0,"evidence":null,"why":"No README, data dictionary, or codebook is named as accompanying the data; variable definitions are not provided inside the article either.","gain":0.0,"priority":"important","scored":false},{"key":"a_controlled_access_for_sensitive","dimension":"A","label":"Gatekeeper for sensitive data","action":"Route sensitive data through an institutional gatekeeper — deposit in a controlled- access repository (dbGaP, EGA) with a Data Access Committee and a published DUA — rather than through the corresponding author's inbox. An author-gated dataset dies with the author's email address, and 'on reasonable request' has been shown repeatedly not to yield data. For sensitive/human clinical / human-subjects data, use a controlled-access repository such as dbGaP or EGA.","anchors":["yes","partial","no"],"verdict":"no","current":0.0,"evidence":null,"why":"The data are from human subjects but are openly accessible with no gatekeeper named; the paper states the work was deemed not human subjects research and access is open.","gain":0.0,"priority":"useful","scored":false},{"key":"a_timeline_retention","dimension":"A","label":"Availability timing & retention","action":"State when the data become available AND how long they will be retained — cite the repository's preservation policy. NIH DMS Element 4 asks for both; most papers give neither.","anchors":["yes","partial","no"],"verdict":"no","current":0.0,"evidence":null,"why":"No sentence in the paper states how long the data will be retained or when they become available beyond the current publication. [majority verdict 'no' (2/4 passes agreed)]","gain":0.0,"priority":"useful","scored":false}],"suggestions":["Attach a standard, machine-readable open licence to the deposit — CC0 or CC BY, which is what Horizon Europe and most funders expect — and print the licence identifier in the paper. 'Free to use' is not a licence: it grants nothing a reuser's institution can rely on.","Release the data in an open, community-standard format (CSV/TSV, JSON, HDF5, NetCDF, FASTQ, VCF, NIfTI…) instead of — or alongside — any proprietary or instrument-native format, and name the format in the paper. A dataset that needs a €2,000 licence to open is not reusable.","Cite the dataset in the reference list like a publication — creator, year, title, repository, DOI/accession — and cite it in-text where it is used. Only a reference- list entry is machine-readable to Crossref/DataCite, and only a citation lets the data earn credit. Cite the clinical / human-subjects repository accession (e.g. from dbGaP or the European Genome-phenome Archive (EGA)) in the reference list.","Replace the statement with the repository template: name the repository and give the accession or DOI (Colavizza category 3). This is the only DAS class associated with a measured citation advantage; 'available on reasonable request' and 'within the article' are not.","Add a 'Data Records' section: itemise every file in the deposit and every variable or sample it holds, with counts and units. Describe the dataset as an object in its own right, not as a by-product of the findings — this is what makes it discoverable to someone who is not looking for your paper."],"model":"deepseek/deepseek-v4-flash","agent_version":"fair_agent_v8","fulltext_source":"unpaywall_pdf"},"fair_model":"deepseek/deepseek-v4-flash","fair_agent_version":"fair_agent_v8","fair_fulltext_source":"unpaywall_pdf","fair_has_llm":true,"fair_computed_at":"2026-07-20T11:13:05.429516Z","clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}