BACKGROUND The phenotypic expression of a high-density lipoprotein (HDL) genetic risk score has been shown to depend upon whether the phenotype (HDL-cholesterol) is high or low relative to its distribution in the population (quantile-dependent expressivity). This may be due to the effects of genetic mutations on HDL-metabolism being concentration dependent. METHOD The purpose of this article is to assess whether some previously reported HDL gene-lifestyle interactions could potentially be attributable to quantile-dependent expressivity. SUMMARY Seventy-three published examples of HDL gene-lifestyle interactions were interpreted from the perspective of quantile-dependent expressivity. These included interactive effects of diet, alcohol, physical activity, adiposity, and smoking with genetic variants associated with the ABCA1, ADH3, ANGPTL4, APOA1, APOA4, APOA5, APOC3, APOE, CETP, CLASP1, CYP7A1, GALNT2, LDLR, LHX1, LIPC, LIPG, LPL, MVK-MMAB, PLTP, PON1, PPARα, SIRT1, SNTA1,and UCP1genes. The selected examples showed larger genetic effect sizes for lifestyle conditions associated with higher vis-à-vis lower average HDL-cholesterol concentrations. This suggests these reported interactions could be the result of selecting subjects for conditions that differentiate high from low HDL-cholesterol (e.g., lean vs. overweight, active vs. sedentary, high-fat vs. high-carbohydrate diets, alcohol drinkers vs. abstainers, nonsmokers vs. smokers) producing larger versus smaller genetic effect sizes. Key Message: Quantile-dependent expressivity provides a potential explanation for some reported gene-lifestyle interactions for HDL-cholesterol. Although overall genetic heritability appears to be quantile specific, this may vary by genetic variant and environmental exposure.

中文翻译：

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涉及高密度脂蛋白胆固醇的分位数依赖性表达和基因生活方式相互作用

背景 高密度脂蛋白 (HDL) 遗传风险评分的表型表达已被证明取决于表型（HDL-胆固醇）相对于其在人群中的分布（分位数依赖性表达）是高还是低。这可能是由于基因突变对 HDL 代谢的影响是浓度依赖性的。方法 本文的目的是评估一些先前报道的 HDL 基因-生活方式相互作用是否可能归因于分位数依赖性表达。总结 从分位数依赖性表达的角度解释了 73 个已发表的 HDL 基因-生活方式相互作用的例子。这些包括饮食、酒精、体力活动、肥胖和吸烟与与 ABCA1、ADH3、ANGPTL4、APOA1、APOA4、APOA5、APOC3、APOE、CETP、CLASP1、CYP7A1、GALNT2、LDLR、LHX1、LIPC、LIPG、LPL、MVK-MMAB、PLTP、PON1、PPARα、SIRT1、SNTA1 和 UCP1 基因。选定的例子表明，与较高的 HDL-胆固醇平均浓度相比，生活方式条件的遗传效应更大。这表明这些报道的相互作用可能是针对区分高与低 HDL 胆固醇的条件（例如，瘦与超重、活跃与久坐、高脂肪与高碳水化合物饮食、饮酒者与戒酒者）选择的结果, 不吸烟者与吸烟者）产生更大与更小的遗传效应大小。关键信息：依赖于分位数的表达能力为一些报道的 HDL-胆固醇的基因-生活方式相互作用提供了一个潜在的解释。