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Genome-wide meta-analysis of phytosterols reveals five novel loci and a detrimental effect on coronary atherosclerosis

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 s...

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Main Authors: Scholz, Markus (Author) , Horn, Katrin (Author) , Pott, Janne (Author) , Gross, Arnd (Author) , Kleber, Marcus E. (Author) , Delgado Gonzales de Kleber, Graciela (Author) , Mishra, Pashupati Prasad (Author) , Kirsten, Holger (Author) , Gieger, Christian (Author) , Müller-Nurasyid, Martina (Author) , Tönjes, Anke (Author) , Kovacs, Peter (Author) , Lehtimäki, Terho (Author) , Raitakari, Olli (Author) , Kähönen, Mika (Author) , Gylling, Helena (Author) , Baber, Ronny (Author) , Isermann, Berend (Author) , Stumvoll, Michael (Author) , Loeffler, Markus (Author) , März, Winfried (Author) , Meitinger, Thomas (Author) , Peters, Annette (Author) , Thiery, Joachim (Author) , Teupser, Daniel (Author) , Ceglarek, Uta (Author)
Format: Article (Journal)
Language:English
Published: 10 January 2022
In: Nature Communications
Year: 2022, Volume: 13, Pages: 1-12
ISSN:2041-1723
DOI:10.1038/s41467-021-27706-6
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s41467-021-27706-6
Verlag, kostenfrei, Volltext: https://www.nature.com/articles/s41467-021-27706-6
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Author Notes:Markus Scholz, Katrin Horn, Janne Pott, Arnd Gross, Marcus E. Kleber, Graciela E. Delgado, Pashupati Prasad Mishra, Holger Kirsten, Christian Gieger, Martina Müller-Nurasyid, Anke Tönjes, Peter Kovacs, Terho Lehtimäki, Olli Raitakari, Mika Kähönen, Helena Gylling, Ronny Baber, Berend Isermann, Michael Stumvoll, Markus Loeffler, Winfried März, Thomas Meitinger, Annette Peters, Joachim Thiery, Daniel Teupser & Uta Ceglarek
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Summary: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.
Item Description:Gesehen am 27.06.2023
Physical Description:Online Resource
ISSN:2041-1723
DOI:10.1038/s41467-021-27706-6

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