Quantile-Dependent Expressivity and Gene-Lifestyle Interactions Involving High-Density Lipoprotein Cholesterol.
Quantile-Dependent Expressivity and Gene-Lifestyle Interactions Involving High-Density Lipoprotein Cholesterol.
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DOI：
10.1159/000511421
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发表时间：
2021
影响因子：
2.6
通讯作者：
Williams PT
中科院分区：
文献类型：
--
作者：
Williams PT
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是高还是低（分位数依赖性表达度）。这可能是由于基因突变对HDL代谢的影响具有浓度依赖性。这篇文章的目的是评估一些以前报道的HDL基因-生活方式的相互作用是否可能归因于分位数依赖的表达。76个已发表的HDL基因与生活方式相互作用的例子从分位数依赖表达的角度进行了解释。这些包括饮食、酒精、体力活动、肥胖和吸烟与ABCA 1、ADH 3、ANGPTL 4、APOA 1、APOA 4、APOA 5、APOC 3、APOE、CETP、CLASP 1、CYP 7A 1、GALNT 2、LDLR、LHX 1、LIPC、LIPG、LPL、MVK-MMAB、PLTP、PON 1、PPARα、SIRT 1、SNTA 1和UCP 1基因相关遗传变异的相互作用。所选的例子表明，与较高的平均HDL-胆固醇浓度相比，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选择区分高HDL-胆固醇和低HDL-胆固醇的受试者的结果（例如，瘦与超重、活动与久坐、高脂肪与高碳水化合物饮食、饮酒者与戒酒者、不吸烟者与吸烟者）产生较大与较小的遗传效应大小。分位数依赖的表达性为一些报道的HDL-胆固醇基因-生活方式相互作用提供了一个潜在的解释。虽然总体遗传遗传力似乎是分位数特异性的，但这可能因遗传变异和环境暴露而异。
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 it distribution in the population (quantile-dependent expressivity). This may be due to the effects of genetic mutations on HDL-metabolism being concentration dependent. The purpose of this article is to assess whether some previously reported HDL gene-lifestyle interactions could potentially be attributable to quantile-dependent expressivity. Seventy-six 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 UCP1 genes. 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, non-smokers vs. smokers) producing larger vs. smaller genetic effect sizes. 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.
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