{"doi":"10.1371/journal.pone.0022070","title":"The Use of Genome-Wide eQTL Associations in Lymphoblastoid Cell Lines to Identify Novel Genetic Pathways Involved in Complex Traits","abstract":null,"journal":"PLoS ONE","year":2011,"id":632006,"datarank":1.9952285286591287,"base_score":3.6635616461296463,"endowment":3.6635616461296463,"self_citation_contribution":0.5495342469194471,"citation_network_contribution":1.4456942817396816,"self_endowment_contribution":0.5495342469194471,"citer_contribution":1.4456942817396816,"corpus_percentile":null,"corpus_rank":null,"citation_count":38,"citer_count":36,"citers_with_citation_signal":33,"citers_with_endowment":33,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":439494,"name":"Jennifer M. Taylor","orcid":"0000-0001-8595-8805","position":1,"is_corresponding":false},{"id":37303,"name":"J. Brent Richards","orcid":"0000-0002-3746-9086","position":2,"is_corresponding":false},{"id":1638084,"name":"Tim Watts","orcid":null,"position":3,"is_corresponding":false},{"id":1638085,"name":"Fredrik H. Pettersson","orcid":null,"position":4,"is_corresponding":false},{"id":840015,"name":"John Broxholme","orcid":"0000-0001-5638-0258","position":5,"is_corresponding":false},{"id":1638086,"name":"Kourosh R. Ahmadi","orcid":null,"position":6,"is_corresponding":false},{"id":90115,"name":"Gabriela L. Surdulescu","orcid":null,"position":7,"is_corresponding":false},{"id":678728,"name":"Ernesto Lowy","orcid":"0000-0001-9312-1159","position":8,"is_corresponding":false},{"id":2351,"name":"Christian Gieger","orcid":"0000-0001-6986-9554","position":9,"is_corresponding":false},{"id":1638087,"name":"Chris Newton-Cheh","orcid":null,"position":10,"is_corresponding":false},{"id":21973,"name":"Markus Perola","orcid":"0000-0003-4842-1667","position":11,"is_corresponding":false},{"id":24551,"name":"Nicole Soranzo","orcid":"0000-0003-1095-3852","position":12,"is_corresponding":false},{"id":24664,"name":"Ida Surakka","orcid":"0000-0002-6669-5541","position":13,"is_corresponding":false},{"id":21993,"name":"Cecilia M. Lindgren","orcid":"0000-0002-4903-9374","position":14,"is_corresponding":false},{"id":40170,"name":"Jiannis Ragoussis","orcid":"0000-0002-8515-0934","position":15,"is_corresponding":false},{"id":16092,"name":"Andrew P. Morris","orcid":"0000-0002-6805-6014","position":16,"is_corresponding":false},{"id":6120,"name":"Lon R. Cardon","orcid":null,"position":17,"is_corresponding":false},{"id":104582,"name":"Tim D. Spector","orcid":"0000-0002-9795-0365","position":18,"is_corresponding":false},{"id":270859,"name":"Krina T. Zondervan","orcid":"0000-0002-0275-9905","position":19,"is_corresponding":false},{"id":544189,"name":"Josine L. Min","orcid":"0000-0003-4456-9824","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"The Use of Genome-Wide eQTL Associations in Lymphoblastoid Cell Lines to Identify Novel Genetic Pathways Involved in Complex Traits","abstract":"The integrated analysis of genotypic and expression data for association with complex traits could identify novel genetic pathways involved in complex traits. We profiled 19,573 expression probes in Epstein-Barr virus-transformed lymphoblastoid cell lines (LCLs) from 299 twins and correlated these with 44 quantitative traits (QTs). For 939 expressed probes correlating with more than one QT, we investigated the presence of eQTL associations in three datasets of 57 CEU HapMap founders and 86 unrelated twins. Genome-wide association analysis of these probes with 2.2 m SNPs revealed 131 potential eQTLs (1,989 eQTL SNPs) overlapping between the HapMap datasets, five of which were in cis (58 eQTL SNPs). We then tested 535 SNPs tagging the eQTL SNPs, for association with the relevant QT in 2,905 twins. We identified nine potential SNP-QT associations (P<0.01) but none significantly replicated in five large consortia of 1,097-16,129 subjects. We also failed to replicate previous reported eQTL associations with body mass index, plasma low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides levels derived from lymphocytes, adipose and liver tissue. Our results and additional power calculations suggest that proponents may have been overoptimistic in the power of LCLs in eQTL approaches to elucidate regulatory genetic effects on complex traits using the small datasets generated to date. Nevertheless, larger tissue-specific expression data sets relevant to specific traits are becoming available, and should enable the adoption of similar integrated analyses in the near future.","is_dataset_classified":null,"base_score":3.6635616461296463,"endowment":3.6635616461296463,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"21789213","pmcid":"PMC3137612","openalex_id":"https://openalex.org/W1971104826","authors":[],"funders":[{"funder_name":"Wellcome Trust","grant_id":"064890","title":null},{"funder_name":"Wellcome Trust","grant_id":"090532","title":null},{"funder_name":"Wellcome Trust","grant_id":"085235","title":null},{"funder_name":"Wellcome Trust","grant_id":"081682","title":null},{"funder_name":"Wellcome Trust","grant_id":"unidentified","title":"unidentified"}],"total_grants":5,"fwci":3.7047,"citation_percentile":0.93170009,"influential_citations":0,"citation_trend":[{"year":2012,"count":6},{"year":2013,"count":9},{"year":2014,"count":5},{"year":2015,"count":5},{"year":2016,"count":1},{"year":2017,"count":1},{"year":2018,"count":3},{"year":2019,"count":4},{"year":2020,"count":2},{"year":2021,"count":1},{"year":2023,"count":1}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0022070&type=printable","host_type":"journal"},{"url":"https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0022070&type=printable","host_type":"publisher"},{"url":"http://dx.plos.org/10.1371/journal.pone.0022070","host_type":"publisher"},{"url":"https://doi.org/10.1371/journal.pone.0022070","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/21789213","host_type":"repository"},{"url":"http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.349.3639","host_type":""},{"url":"https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0022070","host_type":"repository"},{"url":"https://doaj.org/article/982c18574fb2437d82a27dcf7bdb2ea8","host_type":"repository"},{"url":"http://epubs.surrey.ac.uk/825176/","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/3137612","host_type":"repository"},{"url":"https://figshare.com/articles/The_Use_of_Genome_Wide_eQTL_Associations_in_Lymphoblastoid_Cell_Lines_to_Identify_Novel_Genetic_Pathways_Involved_in_Complex_Traits/135140","host_type":"repository"},{"url":"http://hdl.handle.net/10138/165674","host_type":"journal"},{"url":"https://kclpure.kcl.ac.uk/portal/en/publications/586ba84c-02f4-4f9f-84f6-b8f518192017","host_type":"repository"},{"url":"https://push-zb.helmholtz-muenchen.de/frontdoor.php?source_opus=6162","host_type":"repository"},{"url":"https://ora.ox.ac.uk/objects/uuid:4af8403d-8b2c-4129-9e0c-95f35946615e","host_type":"repository"},{"url":"http://www.julkari.fi/handle/10024/107635","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC3137612","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC3137612?pdf=render","host_type":"Europe_PMC"},{"url":"http://dx.doi.org/10.1371/journal.pone.0022070","host_type":""},{"url":"https://dx.doi.org/10.1371/journal.pone.0022070","host_type":""},{"url":"https://openresearch.surrey.ac.uk/esploro/outputs/journalArticle/The-use-of-genome-wide-eQTL-associations/99512656202346","host_type":""},{"url":"https://publications.scilifelab.se/publication/dc16b55f3b534d71ad478a06bb55ee88","host_type":""},{"url":"https://doi.org/https://doi.org/10.1371/journal.pone.0022070","host_type":""}],"fields_of_study":["Genetic Associations and Epidemiology","Epigenetics and DNA Methylation","Genetic Syndromes and Imprinting","0301 basic medicine","0303 health sciences","03 medical and health sciences","Adult","Aged","Aged, 80 and over","Cell Line","Cohort Studies","Databases, Genetic","Female","Gene Expression Regulation","Gene Regulatory Networks","Genome, Human","Genome-Wide Association Study","Haplotypes","Humans","Inheritance Patterns","Lymphocytes","Middle Aged","Polymorphism, Single Nucleotide","Principal Component Analysis","Quantitative Trait Loci","Quantitative Trait, Heritable","Reproducibility of Results","Sample Size","Young Adult"],"mesh_terms":["Adult","Aged","Aged, 80 and over","Cell Line","Female","Gene Expression Regulation","Haplotypes","Humans","Lymphocytes","Middle Aged","Reproducibility of Results","Cohort Studies","Genome, Human","Sample Size","Quantitative Trait, Heritable","Polymorphism, Single Nucleotide","Principal Component Analysis","Databases, Genetic","Inheritance Patterns","Quantitative Trait Loci","Gene Regulatory Networks","Genome-Wide Association Study","Young Adult"],"keywords":["Expression quantitative trait loci","International HapMap Project","Biology","Single-nucleotide polymorphism","Genome-wide association study","Genetic association","Genetics","Quantitative trait locus","Computational biology","SNP","Genotype","Gene","LOCI","Inheritance Patterns","DISEASE","Cohort Studies","Databases, Genetic","80 and over","Gene Regulatory Networks","Lymphocytes","RISK","Aged, 80 and over","Principal Component Analysis","Genome","Q","R","COMMON VARIANTS","Single Nucleotide","Middle Aged","POPULATIONS","Medicine","Female","MICROARRAY PLATFORMS","Human","Research Article","Adult","NUCLEOTIDE","Science","Quantitative Trait Loci","PHENOTYPES","Polymorphism, Single Nucleotide","576","Cell Line","Databases","Quantitative Trait","Young Adult","Quantitative Trait, Heritable","Genetic","616","Humans","Polymorphism","Heritable","METAANALYSIS","Aged","Genome, Human","Reproducibility of Results","Biomedicine","Gene Expression Regulation","Haplotypes","Sample Size","EXPRESSION ANALYSES"],"sdg_mappings":[{"sdg_number":2,"sdg_label":"2. Zero hunger"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"geo"},{"name":"refsnp"},{"name":"go"},{"name":"igsr"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-06T01:22:58.618371Z","pmid":null,"pmcid":null,"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":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}