Selected Publication:

SHR Neuro Cancer Cardio Lipid Metab Microb

Scholz, M; Horn, K; Pott, J; Gross, A; Kleber, ME; Delgado, GE; Mishra, PP; Kirsten, H; Gieger, C; Muller-Nurasyid, M; Tonjes, A; Kovacs, P; Lehtimaki, T; Raitakari, O; Kahonen, M; Gylling, H; Baber, R; Isermann, B; Stumvoll, M; Loeffler, M; Marz, W; Meitinger, T; Peters, A; Thiery, J; Teupser, D; Ceglarek, U.
Genome-wide meta-analysis of phytosterols reveals five novel loci and a detrimental effect on coronary atherosclerosis
NAT COMMUN. 2022; 13(1): 143 Doi: 10.1038/s41467-021-27706-6 [OPEN ACCESS]
Web of Science PubMed FullText FullText_MUG

 

Co-authors Med Uni Graz

März Winfried

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Abstract:

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 genomewide 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.

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