{"doi":"10.1093/g3journal/jkab394","title":"Analysis of independent cohorts of outbred CFW mice reveals novel loci for behavioral and physiological traits and identifies factors determining reproducibility","abstract":"Combining samples for genetic association is standard practice in human genetic analysis of complex traits, but is rarely undertaken in rodent genetics. Here, using 23 phenotypes and genotypes from two independent laboratories, we obtained a sample size of 3076 commercially available outbred mice and identified 70 loci, more than double the number of loci identified in the component studies. Fine-mapping in the combined sample reduced the number of likely causal variants, with a median reduction in set size of 51%, and indicated novel gene associations, including Pnpo, Ttll6, and GM11545 with bone mineral density, and Psmb9 with weight. However, replication at a nominal threshold of 0.05 between the two component studies was low, with less than one-third of loci identified in one study replicated in the second. In addition to overestimates in the effect size in the discovery sample (Winner's Curse), we also found that heterogeneity between studies explained the poor replication, but the contribution of these two factors varied among traits. Leveraging these observations, we integrated information about replication rates, study-specific heterogeneity, and Winner's Curse corrected estimates of power to assign variants to one of four confidence levels. Our approach addresses concerns about reproducibility and demonstrates how to obtain robust results from mapping complex traits in any genome-wide association study.","journal":"G3 Genes Genomes Genetics","year":2021,"id":191413,"datarank":0.4866727836650776,"base_score":2.639057329615259,"endowment":2.639057329615259,"self_citation_contribution":0.3958585994422889,"citation_network_contribution":0.09081418422278872,"self_endowment_contribution":0.3958585994422889,"citer_contribution":0.09081418422278872,"corpus_percentile":60.655991335963485,"corpus_rank":5087,"citation_count":13,"citer_count":5,"citers_with_citation_signal":4,"citers_with_endowment":4,"datacite_reuse_total":0,"is_dataset":true,"is_dataset_confidence":0.5852,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":58.3333,"fair_percentile":72.8829104249465,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":572286,"name":"Shyam Gopalakrishnan","orcid":"0000-0002-2004-6810","position":1,"is_corresponding":false},{"id":395614,"name":"Clarissa C. Parker","orcid":"0000-0002-0361-7095","position":2,"is_corresponding":false},{"id":676695,"name":"Jérôme Nicod","orcid":"0000-0003-2459-3480","position":3,"is_corresponding":false},{"id":757008,"name":"Richard Mott","orcid":"0000-0002-1022-9330","position":4,"is_corresponding":false},{"id":5204,"name":"Na Cai","orcid":"0000-0001-7496-2075","position":5,"is_corresponding":false},{"id":757009,"name":"Arimantas Lionikas","orcid":"0000-0002-0052-6171","position":6,"is_corresponding":false},{"id":552533,"name":"R. W. Davies","orcid":"0000-0002-2252-0862","position":7,"is_corresponding":false},{"id":230002,"name":"Abraham A. Palmer","orcid":"0000-0003-3634-0747","position":8,"is_corresponding":false},{"id":70594,"name":"Jonathan Flint","orcid":"0000-0002-9427-4429","position":9,"is_corresponding":false},{"id":757007,"name":"Jennifer Zou","orcid":"0000-0002-2045-3272","position":0,"is_corresponding":true}],"reference_count":59,"raw_metadata":null,"created_at":"2026-07-18T23:49:35.285023Z","pmid":"34791208","pmcid":"PMC8728023","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":20.0,"fair_r":50.0,"fair_zscore":0.9454,"fair_rationale":{"fair_score":58.33,"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":0.5,"verdict":"partial","evidence":"Raw data from our study is deposited in Dryad: https://datadryad.org/stash/share/P3DJwz6Ligfti43XmQcQAWzLQaN7a3Rt8S7y5KMx90g","grounded":true,"rationale":"The identifier is a web URL, not a persistent identifier scheme (DOI, Handle, ARK, or repository accession). [majority verdict 'partial' (4/5 passes agreed)]","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":"Dryad","grounded":true,"rationale":"The paper names Dryad, a recognized data repository, as the holder of the data. [majority verdict 'yes' (4/5 passes agreed)]","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":1.0,"verdict":"yes","evidence":"The authors affirm that all data necessary for confirming the conclusions of the article are present within the article, figures, and tables. The data and results presented in this paper require no additional permissions for use. Raw data from our study is deposited in Dryad: https://datadryad.org/stash/share/P3DJwz6Ligfti43XmQcQAWzLQaN7a3Rt8S7y5KMx90g","grounded":true,"rationale":"The statement points at a repository record with a link, corresponding to Colavizza category 3. [majority verdict 'yes' (4/5 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":null,"grounded":false,"rationale":"No sentence in the text states what the dataset contains or how large it is; only the study's methods and findings are described. [majority verdict 'no' (4/5 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":"Raw data from our study is deposited in Dryad: https://datadryad.org/stash/share/P3DJwz6Ligfti43XmQcQAWzLQaN7a3Rt8S7y5KMx90g","grounded":true,"rationale":"The dataset's identifier (URL) appears only in the body text, not in the reference list. [majority verdict 'partial' (4/5 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":"The data and results presented in this paper require no additional permissions for use. Raw data from our study is deposited in Dryad: https://datadryad.org/stash/share/P3DJwz6Ligfti43XmQcQAWzLQaN7a3Rt8S7y5KMx90g","grounded":true,"rationale":"The data are deposited in an open repository with no stated precondition.","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":"The data and results presented in this paper require no additional permissions for use.","grounded":true,"rationale":"The paper states that the data require no additional permissions, which is a natural-language label for open access.","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 study does not involve sensitive or human-subject data, and no gatekeeper is named.","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 remain available or when they become obtainable. [majority verdict 'no' (3/5 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":20.0,"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 token is named for the released data.","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":0.0,"verdict":"no","evidence":null,"grounded":false,"rationale":"No data or metadata community standard (e.g., MIAME, BIDS, or an ontology) is named in the text. [majority verdict 'no' (4/5 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":"Code used to perform the analyses in this paper can be found at https://github.com/jzou1115/CFW_code","grounded":true,"rationale":"The paper provides a URL identifier for the code, which is a resource other than the dataset. [majority verdict 'yes' (4/5 passes agreed)]","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":50.0,"criteria":[{"key":"r_reuse_license","label":"Reuse licence","kind":"llm","weight":2.0,"fraction":0.0,"verdict":"no","evidence":null,"grounded":false,"rationale":"No reuse license or terms document is named for the data.","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":1.0,"verdict":"yes","evidence":"The activity of the OX mice was recorded at 16 weeks after placement into a new plastic home cage (46 cm×15 cm×21 cm) using a photoactivity system from San Diego Instruments","grounded":true,"rationale":"The paper names specific instruments and software used to produce the data. [majority verdict 'yes' (4/5 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":0.5,"verdict":"partial","evidence":"Supplementary Data S1 lists the mean and standard deviation of all measures obtained in both studies and the covariates included in the linear model to calculate the residuals.","grounded":true,"rationale":"Variable definitions are provided in a supplementary table inside the article, not as a documentation file shipped with the data. [majority verdict 'partial' (3/5 passes agreed)]","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":0.0,"verdict":"no","evidence":null,"grounded":false,"rationale":"Neither a version token nor a date is given to pin the snapshot of the data. [majority verdict 'no' (3/5 passes agreed)]","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":"Code used to perform the analyses in this paper can be found at https://github.com/jzou1115/CFW_code","grounded":true,"rationale":"A machine-resolvable code repository URL is provided. [majority verdict 'yes' (3/5 passes agreed)]","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":"National Institutes of Health grants [R01MH115979 (J.F.), R01GM097737 and P50DA037844 (A.A.P)]","grounded":true,"rationale":"Grant numbers are attached to named funders. [majority verdict 'yes' (4/5 passes agreed)]","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 reuse license or terms document is named for the data.","gain":16.67,"priority":"essential","scored":true},{"key":"f_dataset_pid","dimension":"F","label":"Persistent identifier for the data","action":"Mint or cite a persistent identifier for the dataset — a repository DOI or an accession from a registered repository — and print it in the paper. A bare URL is not persistent: it is the single most common cause of a dead data link five years after publication. For neuroimaging data, deposit in OpenNeuro or NeuroVault.","anchors":["yes","partial","no"],"verdict":"partial","current":0.5,"evidence":"Raw data from our study is deposited in Dryad: https://datadryad.org/stash/share/P3DJwz6Ligfti43XmQcQAWzLQaN7a3Rt8S7y5KMx90g","why":"The identifier is a web URL, not a persistent identifier scheme (DOI, Handle, ARK, or repository accession). [majority verdict 'partial' (4/5 passes agreed)]","gain":8.33,"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. Prefer open neuroimaging formats such as NIfTI or BIDS.","anchors":["yes","partial","no"],"verdict":"no","current":0.0,"evidence":null,"why":"No file format token is named for the released data.","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 neuroimaging repository accession (e.g. from OpenNeuro or NeuroVault) in the reference list.","anchors":["yes","partial","no"],"verdict":"partial","current":0.5,"evidence":"Raw data from our study is deposited in Dryad: https://datadryad.org/stash/share/P3DJwz6Ligfti43XmQcQAWzLQaN7a3Rt8S7y5KMx90g","why":"The dataset's identifier (URL) appears only in the body text, not in the reference list. [majority verdict 'partial' (4/5 passes agreed)]","gain":4.17,"priority":"important","scored":true},{"key":"r_versioning","dimension":"R","label":"Snapshot identified","action":"Version the deposit and cite the exact version analysed (a version-specific DOI, or an accession with its version suffix). A reader reproducing your work against 'the current release' is reproducing it against a different dataset.","anchors":["yes","partial","no"],"verdict":"no","current":0.0,"evidence":null,"why":"Neither a version token nor a date is given to pin the snapshot of the data. [majority verdict 'no' (3/5 passes agreed)]","gain":4.17,"priority":"useful","scored":true},{"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":null,"why":"No sentence in the text states what the dataset contains or how large it is; only the study's methods and findings are described. [majority verdict 'no' (4/5 passes agreed)]","gain":0.0,"priority":"essential","scored":false},{"key":"i_community_standard_vocabulary","dimension":"I","label":"Community standard / vocabulary","action":"Adopt and NAME your domain's data standard — the minimum-information checklist, metadata schema, or ontology your community uses (MIAME/MINSEQE, ISA-Tab, BIDS, an OBO ontology, HL7 FHIR/OMOP) — and say which one you followed. A reporting checklist standardises your paper; it does nothing for your data. In neuroimaging, describe the data with BIDS, NIfTI or DICOM.","anchors":["yes","partial","no"],"verdict":"no","current":0.0,"evidence":null,"why":"No data or metadata community standard (e.g., MIAME, BIDS, or an ontology) is named in the text. [majority verdict 'no' (4/5 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":"partial","current":0.5,"evidence":"Supplementary Data S1 lists the mean and standard deviation of all measures obtained in both studies and the covariates included in the linear model to calculate the residuals.","why":"Variable definitions are provided in a supplementary table inside the article, not as a documentation file shipped with the data. [majority verdict 'partial' (3/5 passes agreed)]","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.","anchors":["yes","partial","no"],"verdict":"no","current":0.0,"evidence":null,"why":"The study does not involve sensitive or human-subject data, and no gatekeeper is named.","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 remain available or when they become obtainable. [majority verdict 'no' (3/5 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.","Mint or cite a persistent identifier for the dataset — a repository DOI or an accession from a registered repository — and print it in the paper. A bare URL is not persistent: it is the single most common cause of a dead data link five years after publication. For neuroimaging data, deposit in OpenNeuro or NeuroVault.","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. Prefer open neuroimaging formats such as NIfTI or BIDS.","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 neuroimaging repository accession (e.g. from OpenNeuro or NeuroVault) in the reference list.","Version the deposit and cite the exact version analysed (a version-specific DOI, or an accession with its version suffix). A reader reproducing your work against 'the current release' is reproducing it against a different dataset."],"model":"deepseek/deepseek-v4-flash","agent_version":"fair_agent_v8","fulltext_source":"epmc_xml"},"fair_model":"deepseek/deepseek-v4-flash","fair_agent_version":"fair_agent_v8","fair_fulltext_source":"epmc_xml","fair_has_llm":true,"fair_computed_at":"2026-07-20T12:13:25.317909Z","clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}