Quantile-specific heritability of serum growth factor concentrations

“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.
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.
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).
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.

“分位数依赖性表达（Quantile-dependent expressivity）”指当遗传变异的效应大小取决于表型（如生长因子浓度）相对于其分布的高低水平时的现象。
本研究对弗雷明汉心脏研究（Framingham Heart Study）的家系样本应用分位数回归分析，旨在明确血管内皮生长因子（vascular endothelial growth factor, VEGF）、肝细胞生长因子（hepatocyte growth factor, HGF）、血管生成素-2、可溶性Tie-2受体（sTie-2）以及VEGFR1（可溶性Flt-1受体，sFlt-1）的浓度遗传力（h²）是否具有分位数特异性。
经年龄与性别校正后，分位数特异性遗传力（±标准误）随VEGF（趋势检验P<10⁻¹⁶）、HGF（趋势检验P=0.0004）、血管生成素-2（趋势检验P=0.0002）、sTie-2（趋势检验P=1.2×10⁻⁵）及sFlt-1（趋势检验P=0.04）的分布百分位数升高而递增。
VEGF、HGF、血管生成素-2、sTie-2及sFlt-1的浓度遗传力具有分位数依赖性。这或可解释此前报道的遗传位点（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、糖尿病视网膜病变以及贝伐珠单抗治疗在影响VEGF浓度过程中存在的交互作用。