Williams Paul T
Molecular Biophysics & Integrated Bioimaging, Lawrence Berkeley National Laboratory, Berkeley, CA, United States of America.
PeerJ. 2020 May 15;8:e9145. doi: 10.7717/peerj.9145. eCollection 2020.
"Quantile-dependent expressivity" refers to a genetic effect that is dependent upon whether the phenotype (e.g., spirometric data) is high or low relative to its population distribution. Forced vital capacity (FVC), forced expiratory volume in 1 second (FEV), and the FEV/FVC ratio are moderately heritable spirometric traits. The aim of the analyses is to test whether their heritability ( ) is constant over all quantiles of their distribution.
Quantile regression was applied to the mean age, sex, height and smoking-adjusted spirometric data over multiple visits in 9,993 offspring-parent pairs and 1,930 sibships from the Framingham Heart Study to obtain robust estimates of offspring-parent (β), offspring-midparent (β), and full-sib regression slopes (β). Nonparametric significance levels were obtained from 1,000 bootstrap samples. βs were used as simple indicators of quantile-specific heritability (i.e., = 2β/(1+r), where r was the correlation between spouses).
β ± standard error (SE) decreased by 0.0009 ± 0.0003 ( = 0.003) with every one-percent increment in the population distribution of FEV/FVC, i.e., β ± SE were: 0.182 ± 0.031, 0.152 ± 0.015; 0.136 ± 0.011; 0.121 ± 0.013; and 0.099 ± 0.013 at the 10th, 25th, 50th, 75th, and 90th percentiles of the FEV/FVC distribution, respectively. These correspond to ± SEs of 0.350 ± 0.060 at the 10th, 0.292 ± 0.029 at the 25th, 0.262 ± 0.020 at the 50th, 0.234 ± 0.025 at the 75th, and 0.191 ± 0.025 at the 90th percentiles of the FEV/FVC ratio. Maximum mid-expiratory flow (MMEF) ± SEs increased 0.0025 ± 0.0007 ( = 0.0004) with every one-percent increment in its distribution, i.e.: 0.467 ± 0.046, 0.467 ± 0.033, 0.554 ± 0.038, 0.615 ± 0.042, and 0.675 ± 0.060 at the 10th, 25th, 50th, 75th, and 90th percentiles of its distribution. This was due to forced expiratory flow at 75% of FVC (FEF75%), whose quantile-specific increased an average of 0.0042 ± 0.0008 for every one-percent increment in its distribution. It is speculated that previously reported gene-environment interactions may be partially attributable to quantile-specific , i.e., greater heritability in individuals with lower FEV/FVC due to smoking or airborne particles exposure vs. nonsmoking, unexposed individuals.
Heritabilities of FEV/FVC, MMEF, and FEF75% from quantile-regression of offspring-parent and sibling spirometric data suggest their quantile-dependent expressivity.
“分位数依赖表达性”指的是一种遗传效应，该效应取决于表型（如肺功能数据）相对于其总体分布是高还是低。用力肺活量（FVC）、第1秒用力呼气量（FEV）以及FEV/FVC比值是具有中等遗传性的肺功能指标。分析的目的是检验它们的遗传率（ ）在其分布的所有分位数上是否恒定。
对来自弗雷明汉心脏研究的9993对亲子对和1930个同胞组多次访视的平均年龄、性别、身高和经吸烟调整后的肺功能数据应用分位数回归，以获得亲子（β）、子代 - 中亲（β）和全同胞回归斜率（β）的稳健估计值。非参数显著性水平来自1000个自助抽样样本。β用作分位数特异性遗传率的简单指标（即 = 2β/(1 + r)，其中r是配偶之间的相关性）。
随着FEV/FVC总体分布每增加1%，β ± 标准误（SE）降低0.0009 ± 0.0003（ = 0.003），即FEV/FVC分布的第10、25、50、75和90百分位数处的β ± SE分别为：0.182 ± 0.031、0.152 ± 0.015、0.136 ± 0.011、0.121 ± 0.013和90.099 ± 0.013。这些分别对应于FEV/FVC比值第10、25、50、75和90百分位数处的 ± SE为0.350 ± 0.060、0.292 ± 0.029、0.262 ± 0.020、0.234 ± 0.025和0.191 ± 0.025。最大呼气中期流速（MMEF） ± SE随着其分布每增加1%而增加0.0025 ± 0.0007（ = 0.0004），即在其分布的第10、25、50、75和90百分位数处分别为：0.467 ± 0.046、0.467 ± 0.033、0.554 ± 0.038、0.615 ± 0.042和0.675 ± 0.060。这是由于FVC的75%时的用力呼气流量（FEF75%），其分位数特异性 随着其分布每增加1%平均增加0.0042 ± 0.0008。据推测，先前报道的基因 - 环境相互作用可能部分归因于分位数特异性 ，即与未吸烟、未暴露个体相比，由于吸烟或接触空气传播颗粒导致FEV/FVC较低的个体具有更高的遗传率。
来自亲子和同胞肺功能数据分位数回归的FEV/FVC、MMEF和FEF75%的遗传率表明它们具有分位数依赖表达性。
