Objective. “Quantile-dependent expressivity” occurs when the effect size of a genetic variant depends upon whether the phenotype (e.g., serum uric acid) is high or low relative to its distribution. Analyses were performed to test whether serum uric acid heritability is quantile-specific and whether this could explain some reported gene-environment interactions. Methods. Serum uric acid concentrations were analyzed from 2151 sibships and 12,068 offspring-parent pairs from the Framingham Heart Study. Quantile-specific heritability from offspring-parent regression slopes () and full-sib regression slopes () was robustly estimated by quantile regression with nonparametric significance assigned from 1000 bootstrap samples. Results. Quantile-specific (±SE) increased with increasing percentiles of the offspring’s sex- and age-adjusted uric acid distribution when estimated from at the 10^th, at the 25^th, at the 50^th, at the 75^th, and at the 90^th percentile and when estimated from . This is consistent with the larger genetic effect size of (1) the SLC2A9 rs11722228 polymorphism in gout patients vs. controls, (2) the ABCG2 rs2231142 polymorphism in men vs. women, (3) the SLC2A9 rs13113918 polymorphism in obese patients prior to bariatric surgery vs. two-year postsurgery following 29 kg weight loss, (4) the ABCG2 rs6855911 polymorphism in obese vs. nonobese women, and (5) the LRP2 rs2544390 polymorphism in heavier drinkers vs. abstainers. Quantile-dependent expressivity may also explain the larger genetic effect size of an SLC2A9/PKD2/ABCG2 haplotype for high vs. low intakes of alcohol, chicken, or processed meats. Conclusions. Heritability of serum uric acid concentrations is quantile-specific.

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血清尿酸浓度的分位数依赖性表达

目标。当遗传变异的影响大小取决于表型（例如血清尿酸）相对于其分布是高还是低时，就会出现“分位数依赖性表达”。进行了分析以测试血清尿酸遗传力是否具有分位数特异性以及这是否可以解释一些报道的基因-环境相互作用。方法。来自弗雷明汉心脏研究的 2151 对同胞和 12,068 对后代-父母对的血清尿酸浓度进行了分析。来自后代 - 父母回归斜率的分位数特定遗传力（)和全同胞回归斜率 ()是通过分位数回归稳健估计的，从 1000 个引导样本中分配了非参数显着性。结果。分位数特异性(±SE) 随着后代性别和年龄调整的尿酸分布百分位数的增加而增加10^日，25^日，在第 50^次，在第 75^次，和在第 90^个百分位数处，当估计来自. 这与 (1)痛风患者与对照组的SLC2A9 rs11722228 多态性，(2)男性与女性的ABCG2 rs2231142 多态性，(3)肥胖患者肥胖前的SLC2A9 rs13113918 多态性的较大遗传效应大小一致手术与减重 29 公斤后两年手术后的对比，(4)肥胖女性与非肥胖女性的ABCG2 rs6855911 多态性，以及 (5)酗酒者与戒酒者的LRP2 rs2544390 多态性。分位数依赖性表达也可以解释SLC2A9 / PKD2 / ABCG2更大的遗传效应大小酒精、鸡肉或加工肉类的高摄入量与低摄入量的单倍型。结论。血清尿酸浓度的遗传性是分位数特异性的。