{"title":"血清生长因子浓度的分位数特异性遗传力。","authors":"Paul T Williams","doi":"10.1080/08977194.2022.2049261","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>\"Quantile-dependent expressivity\" occurs when the effect size of a genetic variant depends upon whether the phenotype (e.g. growth factor concentration) is high or low relative to its distribution.</p><p><strong>Methods: </strong>Quantile-regression analysis was applied to family sets from the Framingham Heart Study to determine whether the heritability (<i>h<sup>2</sup></i>) of vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), angiopoietin-2, and angiopoietin-2 (sTie-2) and VEGFR1 (sFlt-1) receptor concentrations were quantile-specific.</p><p><strong>Results: </strong>Quantile-specific <i>h<sup>2</sup></i> (±SE) increased with increasing percentiles of the age- and sex-adjusted VEGF (<i>P</i><sub>trend</sub><10<sup>-16</sup>), HGF (<i>P</i><sub>trend</sub>=0.0004), angiopoietin-2 (<i>P</i><sub>trend</sub>=0.0002), sTie-2 (<i>P</i><sub>trend</sub>=1.2 × 10<sup>-5</sup>), and sFlt-1 distributions (<i>P</i><sub>trend</sub>=0.04).</p><p><strong>Conclusion: </strong>Heritabilities of VEGF, HGF, angiopoitein-2, sTie-2 and sFlt-1 concentrations are quantile dependent. This may explain reported interactions of genetic loci (rs10738760, rs9472159, rs833061, rs3025039, rs2280789, rs1570360, rs2010963) with metabolic syndrome, diet, recurrent miscarriage, hepatocellular carcinoma, erysipelas, diabetic retinopathy, and bevacizumab treatment in their effect on VEGF concentrations.</p>","PeriodicalId":12782,"journal":{"name":"Growth factors","volume":null,"pages":null},"PeriodicalIF":1.8000,"publicationDate":"2021-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10101221/pdf/nihms-1845547.pdf","citationCount":"1","resultStr":"{\"title\":\"Quantile-specific heritability of serum growth factor concentrations.\",\"authors\":\"Paul T Williams\",\"doi\":\"10.1080/08977194.2022.2049261\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>\\\"Quantile-dependent expressivity\\\" occurs when the effect size of a genetic variant depends upon whether the phenotype (e.g. growth factor concentration) is high or low relative to its distribution.</p><p><strong>Methods: </strong>Quantile-regression analysis was applied to family sets from the Framingham Heart Study to determine whether the heritability (<i>h<sup>2</sup></i>) of vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), angiopoietin-2, and angiopoietin-2 (sTie-2) and VEGFR1 (sFlt-1) receptor concentrations were quantile-specific.</p><p><strong>Results: </strong>Quantile-specific <i>h<sup>2</sup></i> (±SE) increased with increasing percentiles of the age- and sex-adjusted VEGF (<i>P</i><sub>trend</sub><10<sup>-16</sup>), HGF (<i>P</i><sub>trend</sub>=0.0004), angiopoietin-2 (<i>P</i><sub>trend</sub>=0.0002), sTie-2 (<i>P</i><sub>trend</sub>=1.2 × 10<sup>-5</sup>), and sFlt-1 distributions (<i>P</i><sub>trend</sub>=0.04).</p><p><strong>Conclusion: </strong>Heritabilities of VEGF, HGF, angiopoitein-2, sTie-2 and sFlt-1 concentrations are quantile dependent. This may explain reported interactions of genetic loci (rs10738760, rs9472159, rs833061, rs3025039, rs2280789, rs1570360, rs2010963) with metabolic syndrome, diet, recurrent miscarriage, hepatocellular carcinoma, erysipelas, diabetic retinopathy, and bevacizumab treatment in their effect on VEGF concentrations.</p>\",\"PeriodicalId\":12782,\"journal\":{\"name\":\"Growth factors\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.8000,\"publicationDate\":\"2021-02-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10101221/pdf/nihms-1845547.pdf\",\"citationCount\":\"1\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Growth factors\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1080/08977194.2022.2049261\",\"RegionNum\":4,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Growth factors","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1080/08977194.2022.2049261","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
Quantile-specific heritability of serum growth factor concentrations.
Background: "Quantile-dependent expressivity" occurs when the effect size of a genetic variant depends upon whether the phenotype (e.g. growth factor concentration) is high or low relative to its distribution.
Methods: Quantile-regression analysis was applied to family sets from the Framingham Heart Study to determine whether the heritability (h2) of vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), angiopoietin-2, and angiopoietin-2 (sTie-2) and VEGFR1 (sFlt-1) receptor concentrations were quantile-specific.
Results: Quantile-specific h2 (±SE) increased with increasing percentiles of the age- and sex-adjusted VEGF (Ptrend<10-16), HGF (Ptrend=0.0004), angiopoietin-2 (Ptrend=0.0002), sTie-2 (Ptrend=1.2 × 10-5), and sFlt-1 distributions (Ptrend=0.04).
Conclusion: Heritabilities of VEGF, HGF, angiopoitein-2, sTie-2 and sFlt-1 concentrations are quantile dependent. This may explain reported interactions of genetic loci (rs10738760, rs9472159, rs833061, rs3025039, rs2280789, rs1570360, rs2010963) with metabolic syndrome, diet, recurrent miscarriage, hepatocellular carcinoma, erysipelas, diabetic retinopathy, and bevacizumab treatment in their effect on VEGF concentrations.
期刊介绍:
Growth Factors is an international and interdisciplinary vehicle publishing new knowledge and findings on the regulators of cell proliferation, differentiation and survival. The Journal will publish research papers, short communications and reviews on current developments in cell biology, biochemistry, physiology or pharmacology of growth factors, cytokines or hormones which improve our understanding of biology or medicine. Among the various fields of study topics of particular interest include: •Stem cell biology •Growth factor physiology •Structure-activity relationships •Drug development studies •Clinical applications