Institute for Medical Informatics, Statistics and Epidemiology, Medical Faculty, University of Leipzig, Leipzig, Germany.
LIFE Research Center for Civilization Diseases, Medical Faculty, University of Leipzig, Leipzig, Germany.
Nat Commun. 2022 Jan 10;13(1):143. doi: 10.1038/s41467-021-27706-6.
Phytosterol serum concentrations are under tight genetic control. The relationship between phytosterols and coronary artery disease (CAD) is controversially discussed. We perform a genome-wide meta-analysis of 32 phytosterol traits reflecting resorption, cholesterol synthesis and esterification in six studies with up to 9758 subjects and detect ten independent genome-wide significant SNPs at seven genomic loci. We confirm previously established associations at ABCG5/8 and ABO and demonstrate an extended locus heterogeneity at ABCG5/8 with different functional mechanisms. New loci comprise HMGCR, NPC1L1, PNLIPRP2, SCARB1 and APOE. Based on these results, we perform Mendelian Randomization analyses (MR) revealing a risk-increasing causal relationship of sitosterol serum concentrations and CAD, which is partly mediated by cholesterol. Here we report that phytosterols are polygenic traits. MR add evidence of both, direct and indirect causal effects of sitosterol on CAD.
植物固醇血清浓度受到严格的遗传控制。植物固醇与冠状动脉疾病（CAD）之间的关系存在争议。我们对六个研究中的 32 种反映吸收、胆固醇合成和酯化的植物固醇特征进行了全基因组荟萃分析，这些研究最多包含 9758 名受试者，在七个基因组位点检测到 10 个独立的全基因组显著 SNP。我们证实了 ABCG5/8 和 ABO 中先前已建立的关联，并证明 ABCG5/8 中的位点异质性具有不同的功能机制。新的位点包括 HMGCR、NPC1L1、PNLIPRP2、SCARB1 和 APOE。基于这些结果，我们进行了孟德尔随机化分析（MR），结果表明植物固醇血清浓度与 CAD 之间存在风险增加的因果关系，而胆固醇在其中起部分中介作用。我们的研究表明，植物固醇是多基因特征。MR 进一步证实了植物固醇对 CAD 的直接和间接因果关系。
