Williams Paul T
Molecular Biophysics & Integrated Bioimaging, Lawrence Berkeley National Laboratory, Berkeley, CA, United States of America.
PeerJ. 2020 Oct 14;8:e10099. doi: 10.7717/peerj.10099. eCollection 2020.
"Quantile-dependent expressivity" occurs when the effect size of a genetic variant depends upon whether the phenotype (e.g. adiponectin) is high or low relative to its distribution. We have previously shown that the heritability ( ) of adiposity, lipoproteins, postprandial lipemia, pulmonary function, and coffee and alcohol consumption are quantile-specific. Whether adiponectin heritability is quantile specific remains to be determined.
Plasma adiponectin concentrations from 4,182 offspring-parent pairs and 1,662 sibships from the Framingham Heart Study were analyzed. Quantile-specific heritability from offspring-parent ( , = 2 /(1 + r)) and full-sib regression slopes ( , = {(1 + 8r )-1}/(2r)) were robustly estimated by quantile regression with nonparametric significance assigned from 1,000 bootstrap samples.
Quantile-specific (± SE) increased with increasing percentiles of the offspring's age- and sex-adjusted adiponectin distribution when estimated from ( = 2.2 × 10): 0.30 ± 0.03 at the 10th, 0.33 ± 0.04 at the 25th, 0.43 ± 0.04 at the 50th, 0.55 ± 0.05 at the 75th, and 0.57 ± 0.08 at the 90th percentile, and when estimated from ( = 7.6 × 10): 0.42 ± 0.03 at the 10th, 0.44 ± 0.04 at the 25th, 0.56 ± 0.05 at the 50th, 0.73 ± 0.08 at the 75th, and 0.79 ± 0.11 at the 90th percentile. Consistent with quantile-dependent expressivity, adiponectin's: (1) heritability was greater in women in accordance with their higher adiponection concentrations; (2) relationships to polymorphisms were modified by adiposity in accordance with its adiponectin-lowering effect; (3) response to rosiglitazone was predicted by the 45T> G polymorphism; (4) difference by haplotypes increased linearly with increasing postprandial adiponectin concentrations.
Adiponectin heritability is quantile dependent, which may explain sex-specific heritability, gene-environment and gene-drug interactions, and postprandial response by haplotypes.
当基因变异的效应大小取决于表型（如脂联素）相对于其分布是高还是低时，就会出现“分位数依赖表达性”。我们之前已经表明，肥胖、脂蛋白、餐后血脂、肺功能以及咖啡和酒精消费的遗传力（ ）是特定分位数的。脂联素的遗传力是否是特定分位数的仍有待确定。
分析了来自弗雷明汉心脏研究的4182对后代-父母对和1662个同胞关系中的血浆脂联素浓度。通过分位数回归稳健地估计了后代-父母（ ， = 2 /(1 + r)）和全同胞回归斜率（ ， = {(1 + 8r )-1}/(2r)）的特定分位数遗传力，并从1000个自举样本中分配非参数显著性。
当根据 （ = 2.2 × 10）估计时，特定分位数的 （±标准误）随着后代年龄和性别调整后的脂联素分布百分位数的增加而增加：第10百分位数为0.30 ± 0.03，第25百分位数为0.33 ± 0.04，第50百分位数为0.43 ± 0.04，第75百分位数为0.55 ± 0.05，第90百分位数为0.57 ± 0.08；当根据 （ = 7.6 × 10）估计时：第10百分位数为0.42 ± 0.03，第25百分位数为0.44 ± 0.04，第50百分位数为0.56 ± 0.05，第75百分位数为0.73 ± 0.08，第90百分位数为0.79 ± 0.11。与分位数依赖表达性一致，脂联素的：（1）遗传力在女性中更大，这与其较高的脂联素浓度一致；（2）与 多态性的关系根据其降低脂联素的作用而被肥胖所改变；（3）对罗格列酮的反应由45T>G 多态性预测；（4） 单倍型之间的差异随着餐后脂联素浓度的增加而线性增加。
脂联素遗传力是分位数依赖的，这可能解释了性别特异性遗传力、基因-环境和基因-药物相互作用以及单倍型的餐后反应。
