Background:The increase in serum triglyceride (TG) concentrations in response to a meal is considered a risk factor for cardiovascular disease. We aimed to elucidate the genetics of the postprandial TG response through genome-wide association studies (GWAS).Methods:Participants of the NEO (Netherlands Epidemiology of Obesity) study (n=5630) consumed a liquid mixed meal after an overnight fast. GWAS of fasting and postprandial serum TG at 150 minutes were performed. To identify genetic variation of postprandial TG independent of fasting TG, we calculated the TG response at 150 minutes by the residuals of a nonlinear regression that predicted TG at 150 minutes as a function of fasting TG. Association analyses were adjusted for age, sex, and principal components in a linear regression model. Next, using the identified variants as determinants, we performed linear regression analyses on the residuals of the postprandial response of 149 nuclear magnetic resonance–based metabolite measures.Results:GWAS of fasting TG and postprandial serum TG at 150 minutes resulted in completely overlapping loci, replicating previous GWAS. From GWAS of the TG response, we identified rs7350789-A (allele frequency=0.36), mapping to hepatic lipase (LIPC), to be associated with a smaller increase in TG concentrations at 150 minutes (β=−0.11; P-value=5.1×10⁻⁸). Rs7350789-A was associated with responses of 33 metabolite measures (P-value <1.34×10⁻³), mainly smaller increases of the TG-component in almost all HDL (high-density lipoprotein) subparticles (HDL-TG), a smaller decrease of HDL diameter and smaller increases of most components of VLDL (very low density lipoprotein) subparticles.Conclusions:GWAS of the TG response identified a variant near LIPC as a main contributor to postprandial TG metabolism independent of fasting TG concentrations, resulting in smaller increases of HDL-TG and VLDL subparticles.

中文翻译：

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餐后甘油三酯反应的全基因组关联研究导致 LIPC（肝脂肪酶）的常见遗传变异。

背景：餐后血清甘油三酯 (TG) 浓度升高被认为是心血管疾病的危险因素。我们旨在通过全基因组关联研究 (GWAS) 阐明餐后 TG 反应的遗传学。方法：NEO（荷兰肥胖流行病学）研究 (n=5630) 的参与者在禁食一夜后食用了液体混合餐。在 150 分钟时进行空腹和餐后血清 TG 的 GWAS。为了识别与空腹 TG 无关的餐后 TG 的遗传变异，我们通过非线性回归的残差计算了 150 分钟时的 TG 响应，该非线性回归预测了 150 分钟时的 TG 作为空腹 TG 的函数。在线性回归模型中针对年龄、性别和主要成分调整了关联分析。接下来，使用已识别的变体作为决定因素，我们对 149 项基于核磁共振的代谢物测量的餐后反应残差进行了线性回归分析。结果：空腹 TG 和餐后血清 TG 在 150 分钟的 GWAS 导致完全重叠的基因座，复制了之前的 GWAS。从 TG 反应的 GWAS，我们确定了 rs7350789-A（等位基因频率 = 0.36），映射到肝脂肪酶（LIPC），与 150 分钟时 TG 浓度的较小增加相关（β=-0.11；P值=5.1×10 ^-8）。Rs7350789-A 与 33 种代谢物测量（P值 <1.34×10 ^-3）的反应相关，主要是几乎所有 HDL（高密度脂蛋白）亚颗粒 (HDL-TG) 中 TG 成分的较小增加，较小的降低HDL直径和VLDL（极低密度脂蛋白）的subparticles.Conclusions大多数组件的较小的增加：识别为靠近一个变型中，响应TG的GWAS LIPC作为主要贡献者餐后TG代谢独立空腹TG浓度，导致更小的增加HDL-TG 和 VLDL 亚颗粒。