{"doi":"10.1111/bjh.12366","title":"rs2072135, a low‐penetrance variant for chronic lymphocytic leukaemia?","abstract":"<jats:title>Summary</jats:title><jats:p>Recent multi‐stage genome‐wide association studies (<jats:styled-content style=\"fixed-case\">GWAS</jats:styled-content>) have identified single nucleotide polymorphisms (<jats:styled-content style=\"fixed-case\">SNP</jats:styled-content>s) that are robustly associated with chronic lymphocytic leukaemia (<jats:styled-content style=\"fixed-case\">CLL</jats:styled-content>) risk. Given that most of these <jats:styled-content style=\"fixed-case\">SNP</jats:styled-content>s map to non‐coding regions of the genome, it suggests that the functional basis of many <jats:styled-content style=\"fixed-case\">GWAS</jats:styled-content> signals will be through differential gene expression. By referencing publically accessible expression quantitative trait loci (<jats:styled-content style=\"fixed-case\">eQTL</jats:styled-content>) data on lymphoblastoid cells lines (<jats:styled-content style=\"fixed-case\">LCLs</jats:styled-content>) we have globally demonstrated an association between <jats:styled-content style=\"fixed-case\">GWAS </jats:styled-content><jats:italic>P</jats:italic>‐values and <jats:styled-content style=\"fixed-case\">eQTL</jats:styled-content>s, consistent with much of the variation in <jats:styled-content style=\"fixed-case\">CLL</jats:styled-content> risk being defined by variants impacting on gene expression. To explore using <jats:styled-content style=\"fixed-case\">eQTL</jats:styled-content> data to select <jats:styled-content style=\"fixed-case\">GWAS SNP</jats:styled-content>s for replication, we genotyped rs2072135 (<jats:styled-content style=\"fixed-case\">GWAS </jats:styled-content><jats:italic>P</jats:italic>‐value = 0·0024, <jats:styled-content style=\"fixed-case\">eQTL </jats:styled-content><jats:italic>P</jats:italic>‐value = 1·510<jats:sup>−19</jats:sup>) in five independent case‐control series totalling 1968 cases and 3538 controls. While not attaining statistical significance (combined <jats:italic>P</jats:italic>‐value = 1 × 10<jats:sup>−4</jats:sup>), rs2072135 defines a promising risk locus for <jats:styled-content style=\"fixed-case\">CLL</jats:styled-content>. Incorporating <jats:styled-content style=\"fixed-case\">eQTL</jats:styled-content> information offers an attractive strategy for selecting <jats:styled-content style=\"fixed-case\">SNP</jats:styled-content>s from <jats:styled-content style=\"fixed-case\">GWAS</jats:styled-content> for validation.</jats:p>","journal":"British Journal of Haematology","year":2013,"id":590370,"datarank":0.2759400863022917,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"self_citation_contribution":0.20794415416798362,"citation_network_contribution":0.06799593213430813,"self_endowment_contribution":0.20794415416798362,"citer_contribution":0.06799593213430813,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":3,"citers_with_citation_signal":2,"citers_with_endowment":2,"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":303033,"name":"Helen E. Speedy","orcid":null,"position":1,"is_corresponding":false},{"id":1510518,"name":"Maria Chiara Di Bernardo","orcid":null,"position":2,"is_corresponding":false},{"id":1265839,"name":"Silvia Deaglio","orcid":"0000-0003-0632-5036","position":3,"is_corresponding":false},{"id":21563,"name":"Lidia Karabon","orcid":"0000-0001-8172-0971","position":4,"is_corresponding":false},{"id":21550,"name":"Irena Frydecka","orcid":"0000-0002-4086-4538","position":5,"is_corresponding":false},{"id":1510519,"name":"Dariusz Woszczyk","orcid":null,"position":6,"is_corresponding":false},{"id":814398,"name":"Davide Rossi","orcid":"0000-0002-2837-1597","position":7,"is_corresponding":false},{"id":117799,"name":"Gianluca Gaidano","orcid":null,"position":8,"is_corresponding":false},{"id":614026,"name":"Larry Mansouri","orcid":null,"position":9,"is_corresponding":false},{"id":404954,"name":"Karin E. Smedby","orcid":"0000-0002-2104-3320","position":10,"is_corresponding":false},{"id":215237,"name":"Gunnar Juliusson","orcid":null,"position":11,"is_corresponding":false},{"id":612979,"name":"Richard Rosenquist","orcid":"0000-0002-0211-8788","position":12,"is_corresponding":false},{"id":613852,"name":"Daniel Catovsky","orcid":"0000-0001-6421-1075","position":13,"is_corresponding":false},{"id":254457,"name":"Richard S. Houlston","orcid":"0000-0002-5268-0242","position":14,"is_corresponding":false},{"id":613854,"name":"Georgina P. Sava","orcid":"0000-0001-5904-3978","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"rs2072135, a low‐penetrance variant for chronic lymphocytic leukaemia?","abstract":"<jats:title>Summary</jats:title><jats:p>Recent multi‐stage genome‐wide association studies (<jats:styled-content style=\"fixed-case\">GWAS</jats:styled-content>) have identified single nucleotide polymorphisms (<jats:styled-content style=\"fixed-case\">SNP</jats:styled-content>s) that are robustly associated with chronic lymphocytic leukaemia (<jats:styled-content style=\"fixed-case\">CLL</jats:styled-content>) risk. Given that most of these <jats:styled-content style=\"fixed-case\">SNP</jats:styled-content>s map to non‐coding regions of the genome, it suggests that the functional basis of many <jats:styled-content style=\"fixed-case\">GWAS</jats:styled-content> signals will be through differential gene expression. By referencing publically accessible expression quantitative trait loci (<jats:styled-content style=\"fixed-case\">eQTL</jats:styled-content>) data on lymphoblastoid cells lines (<jats:styled-content style=\"fixed-case\">LCLs</jats:styled-content>) we have globally demonstrated an association between <jats:styled-content style=\"fixed-case\">GWAS </jats:styled-content><jats:italic>P</jats:italic>‐values and <jats:styled-content style=\"fixed-case\">eQTL</jats:styled-content>s, consistent with much of the variation in <jats:styled-content style=\"fixed-case\">CLL</jats:styled-content> risk being defined by variants impacting on gene expression. To explore using <jats:styled-content style=\"fixed-case\">eQTL</jats:styled-content> data to select <jats:styled-content style=\"fixed-case\">GWAS SNP</jats:styled-content>s for replication, we genotyped rs2072135 (<jats:styled-content style=\"fixed-case\">GWAS </jats:styled-content><jats:italic>P</jats:italic>‐value = 0·0024, <jats:styled-content style=\"fixed-case\">eQTL </jats:styled-content><jats:italic>P</jats:italic>‐value = 1·510<jats:sup>−19</jats:sup>) in five independent case‐control series totalling 1968 cases and 3538 controls. While not attaining statistical significance (combined <jats:italic>P</jats:italic>‐value = 1 × 10<jats:sup>−4</jats:sup>), rs2072135 defines a promising risk locus for <jats:styled-content style=\"fixed-case\">CLL</jats:styled-content>. Incorporating <jats:styled-content style=\"fixed-case\">eQTL</jats:styled-content> information offers an attractive strategy for selecting <jats:styled-content style=\"fixed-case\">SNP</jats:styled-content>s from <jats:styled-content style=\"fixed-case\">GWAS</jats:styled-content> for validation.</jats:p>","is_dataset_classified":null,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"23668599","pmcid":null,"openalex_id":"https://openalex.org/W1995613491","authors":[],"funders":[{"funder_name":"Special Program Molecular Clinical Oncology","grant_id":"10007","title":null},{"funder_name":"First AIRC Grant 2012","grant_id":"","title":null},{"funder_name":"Associazione Italiana per la Ricerca sul Cancro Foundation","grant_id":"","title":null}],"total_grants":3,"fwci":0.1549,"citation_percentile":0.52154523,"influential_citations":0,"citation_trend":[{"year":2014,"count":1},{"year":2025,"count":1},{"year":2026,"count":1}],"oa_status":"bronze","license":"http://onlinelibrary.wiley.com/termsAndConditions#vor","oa_locations":[{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/bjh.12366","host_type":"journal"},{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/bjh.12366","host_type":"publisher"},{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1111%2Fbjh.12366","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1111/bjh.12366","host_type":"publisher"},{"url":"https://doi.org/10.1111/bjh.12366","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/23668599","host_type":"repository"},{"url":"https://lup.lub.lu.se/record/3975866","host_type":"repository"}],"fields_of_study":["Chronic Lymphocytic Leukemia Research","Glycosylation and Glycoproteins Research","Immunodeficiency and Autoimmune Disorders","Adult","Aged","Case-Control Studies","Female","Gene Expression","Genetic Predisposition to Disease","Genome-Wide Association Study","Genotype","Humans","Leukemia, Lymphocytic, Chronic, B-Cell","Male","Middle Aged","Penetrance","Polymorphism, Single Nucleotide","Quantitative Trait Loci"],"mesh_terms":["Adult","Aged","Female","Genotype","Humans","Male","Middle Aged","Leukemia, Lymphocytic, Chronic, B-Cell","Gene Expression","Case-Control Studies","Penetrance","Genetic Predisposition to Disease","Polymorphism, Single Nucleotide","Quantitative Trait Loci","Genome-Wide Association Study"],"keywords":["Expression quantitative trait loci","Genome-wide association study","Single-nucleotide polymorphism","Genetic association","Biology","Genetics","Computational biology","Gene","Genotype","Polymorphism","Gene Expression","risk","Chronic Lymphocytic Leukaemia"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"refsnp"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-24T19:03:39.335865Z","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":[]}