血清生长因子浓度的分位数特异性遗传力。
Quantile-specific heritability of serum growth factor concentrations.
机构信息
Lawrence Berkeley National Laboratory, Molecular Biophysics & Integrated Bioimaging Division, Berkeley, CA, USA.
出版信息
Growth Factors. 2021 Feb-Jul;39(1-6):45-58. doi: 10.1080/08977194.2022.2049261. Epub 2022 Mar 21.
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 () 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 (±SE) increased with increasing percentiles of the age- and sex-adjusted VEGF (<10), HGF (=0.0004), angiopoietin-2 (=0.0002), sTie-2 (=1.2 × 10), and sFlt-1 distributions (=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.
背景
“分位数依赖表达性”是指遗传变异的效应大小取决于表型（例如生长因子浓度）相对于其分布是高还是低。
方法
应用分位数回归分析对弗雷明汉心脏研究的家系进行分析，以确定血管内皮生长因子（VEGF）、肝细胞生长因子（HGF）、血管生成素-2 和血管生成素-2（sTie-2）以及血管内皮生长因子受体 1（sFlt-1）浓度的遗传性（）是否具有分位数特异性。
结果
随着年龄和性别调整后的 VEGF（<10）、HGF（=0.0004）、血管生成素-2（=0.0002）、sTie-2（=1.2×10）和 sFlt-1 分布的分位数（%）的增加，分位数特异性（±SE）增加（=0.04）。
结论
VEGF、HGF、血管生成素-2、sTie-2 和 sFlt-1 浓度的遗传性与分位数有关。这可能解释了遗传位点（rs10738760、rs9472159、rs833061、rs3025039、rs2280789、rs1570360、rs2010963）与代谢综合征、饮食、复发性流产、肝细胞癌、丹毒、糖尿病性视网膜病变和贝伐单抗治疗对 VEGF 浓度的影响的相互作用。
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