{"doi":"10.1159/000527048","title":"Quantile-Specific Heritability of Mean Platelet Volume, Leukocyte Count, and Other Blood Cell Phenotypes","abstract":"<b><i>Introduction:</i></b> “Quantile-dependent expressivity” occurs when the effect size of a genetic variant depends upon whether the phenotype (e.g., mean platelet volume, MPV) is high or low relative to its distribution. <b><i>Methods:</i></b> Offspring-parent regression slopes (β<sub>OP</sub>) were estimated by quantile regression, from which quantile-specific heritabilities (<i>h</i><sup>2</sup>) were calculated (<i>h</i><sup>2</sup> = 2β<sub>OP</sub>/[1 + <i>r</i><sub>spouse</sub>]) for blood cell phenotypes in 3,929 parent-offspring pairs from the Framingham Heart Study. <b><i>Results:</i></b> Quantile-specific <i>h</i><sup>2</sup> (±SE) increased with increasing percentiles of the offspring’s age- and sex-adjusted MPV distribution (<i>p</i><sub>linear</sub> = 0.0001): 0.48 ± 0.09 at the 10th, 0.53 ± 0.04 at the 25th, 0.70 ± 0.06 at the 50th, 0.74 ± 0.06 at the 75th, and 0.90 ± 0.12 at the 90th percentile. Quantile-specific <i>h</i><sup>2</sup> also increased with increasing percentiles of the offspring’s white blood cell (WBC, <i>p</i><sub>linear</sub> = 0.002), monocyte (<i>p</i><sub>linear</sub> = 0.01), and eosinophil distributions (<i>p</i><sub>linear</sub> = 0.0005). In contrast, heritibilities of red blood cell (RBC) count, hematocrit (HCT), and hemoglobin (HGB) showed little evidence of quantile dependence. Quantile-dependent expressivity is consistent with gene-environment interactions reported by others, including (1) greater increases in WBC and PLT concentrations in subjects who are glutathione-S-transferase Mu1 (<i>GSTM1</i>) null homozygotes than <i>GSTM1</i> sufficient when exposed to endotoxin; (2) significantly higher WBC count in AA homozygotes than carriers of the G-allele of the glutathione S-transferase P1 (<i>GSTP1</i>) rs1695 polymorphism at low but not high benzene exposure in shoe factory workers; (3) higher WBC counts in TT homozygotes than C-allele carriers of the interleukin-1β (<i>IL1B</i>) c.315C>T polymorphism after undergoing surgery for infective endocarditis but not before surgery. <b><i>Discussion/Conclusion:</i></b> Quantile-dependent expressivity may explain several purported gene-environment interactions involving blood cell phenotypes.","journal":"Lifestyle Genomics","year":2022,"id":294705,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9393,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":356366,"name":"Paul T. Williams","orcid":"0000-0002-4872-4556","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T00:31:01.450041Z","pmid":"36137513","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":[]}