{"title":"平均血小板体积、白细胞计数和其他血细胞表型的分位数特异性遗传性。","authors":"Paul T Williams","doi":"10.1159/000527048","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>\"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.</p><p><strong>Methods: </strong>Offspring-parent regression slopes (βOP) were estimated by quantile regression, from which quantile-specific heritabilities (h2) were calculated (h2 = 2βOP/[1 + rspouse]) for blood cell phenotypes in 3,929 parent-offspring pairs from the Framingham Heart Study.</p><p><strong>Results: </strong>Quantile-specific h2 (±SE) increased with increasing percentiles of the offspring's age- and sex-adjusted MPV distribution (plinear = 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 h2 also increased with increasing percentiles of the offspring's white blood cell (WBC, plinear = 0.002), monocyte (plinear = 0.01), and eosinophil distributions (plinear = 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 (GSTM1) null homozygotes than GSTM1 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 (GSTP1) 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 (IL1B) c.315C>T polymorphism after undergoing surgery for infective endocarditis but not before surgery.</p><p><strong>Discussion/conclusion: </strong>Quantile-dependent expressivity may explain several purported gene-environment interactions involving blood cell phenotypes.</p>","PeriodicalId":18030,"journal":{"name":"Lifestyle Genomics","volume":"15 4","pages":"111-123"},"PeriodicalIF":2.0000,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"1","resultStr":"{\"title\":\"Quantile-Specific Heritability of Mean Platelet Volume, Leukocyte Count, and Other Blood Cell Phenotypes.\",\"authors\":\"Paul T Williams\",\"doi\":\"10.1159/000527048\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>\\\"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.</p><p><strong>Methods: </strong>Offspring-parent regression slopes (βOP) were estimated by quantile regression, from which quantile-specific heritabilities (h2) were calculated (h2 = 2βOP/[1 + rspouse]) for blood cell phenotypes in 3,929 parent-offspring pairs from the Framingham Heart Study.</p><p><strong>Results: </strong>Quantile-specific h2 (±SE) increased with increasing percentiles of the offspring's age- and sex-adjusted MPV distribution (plinear = 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 h2 also increased with increasing percentiles of the offspring's white blood cell (WBC, plinear = 0.002), monocyte (plinear = 0.01), and eosinophil distributions (plinear = 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 (GSTM1) null homozygotes than GSTM1 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 (GSTP1) 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 (IL1B) c.315C>T polymorphism after undergoing surgery for infective endocarditis but not before surgery.</p><p><strong>Discussion/conclusion: </strong>Quantile-dependent expressivity may explain several purported gene-environment interactions involving blood cell phenotypes.</p>\",\"PeriodicalId\":18030,\"journal\":{\"name\":\"Lifestyle Genomics\",\"volume\":\"15 4\",\"pages\":\"111-123\"},\"PeriodicalIF\":2.0000,\"publicationDate\":\"2022-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"1\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Lifestyle Genomics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1159/000527048\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"GENETICS & HEREDITY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Lifestyle Genomics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1159/000527048","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
Quantile-Specific Heritability of Mean Platelet Volume, Leukocyte Count, and Other Blood Cell Phenotypes.
Introduction: "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.
Methods: Offspring-parent regression slopes (βOP) were estimated by quantile regression, from which quantile-specific heritabilities (h2) were calculated (h2 = 2βOP/[1 + rspouse]) for blood cell phenotypes in 3,929 parent-offspring pairs from the Framingham Heart Study.
Results: Quantile-specific h2 (±SE) increased with increasing percentiles of the offspring's age- and sex-adjusted MPV distribution (plinear = 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 h2 also increased with increasing percentiles of the offspring's white blood cell (WBC, plinear = 0.002), monocyte (plinear = 0.01), and eosinophil distributions (plinear = 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 (GSTM1) null homozygotes than GSTM1 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 (GSTP1) 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 (IL1B) c.315C>T polymorphism after undergoing surgery for infective endocarditis but not before surgery.
Discussion/conclusion: Quantile-dependent expressivity may explain several purported gene-environment interactions involving blood cell phenotypes.
期刊介绍：
Lifestyle Genomics aims to provide a forum for highlighting new advances in the broad area of lifestyle-gene interactions and their influence on health and disease. The journal welcomes novel contributions that investigate how genetics may influence a person’s response to lifestyle factors, such as diet and nutrition, natural health products, physical activity, and sleep, amongst others. Additionally, contributions examining how lifestyle factors influence the expression/abundance of genes, proteins and metabolites in cell and animal models as well as in humans are also of interest. The journal will publish high-quality original research papers, brief research communications, reviews outlining timely advances in the field, and brief research methods pertaining to lifestyle genomics. It will also include a unique section under the heading “Market Place” presenting articles of companies active in the area of lifestyle genomics. Research articles will undergo rigorous scientific as well as statistical/bioinformatic review to ensure excellence.
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