A1 Refereed original research article in a scientific journal
Genome-wide meta-analysis of phytosterols reveals five novel loci and a detrimental effect on coronary atherosclerosis
Authors: Scholz Markus, Horn Katrin, Pott Janne, Gross Arnd, Kleber Marcus E., Delgado Graciela E., Mishra Pashupati Prasad, Kirsten Holger, Gieger Christian, Müller-Nurasyid Martina, Tönjes Anke, Kovacs Peter, Lehtimäki Terho, Raitakari Olli, Kähönen Mika, Gylling Helena, Baber Ronny, Isermann Berend, Stumvoll Michael, Loeffler Markus, März Winfried, Meitinger Thomas, Peters Annette, Thiery Joachim, Teupser Daniel, Ceglarek Uta
Publisher: Nature Portfolio
Publication year: 2022
Journal: Nature Communications
Journal name in source: NATURE COMMUNICATIONS
Journal acronym: NAT COMMUN
Article number: 143
Volume: 13
Number of pages: 12
eISSN: 2041-1723
DOI: https://doi.org/10.1038/s41467-021-27706-6
Web address : https://doi.org/10.1038/s41467-021-27706-6
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/176965077
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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