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Scholz, M.* ; Horn, K.* ; Pott, J.* ; Gross, A.* ; Kleber, M.E.* ; Delgado, G.E.* ; Mishra, P.P.* ; Kirsten, H.* ; Gieger, C. ; Müller-Nurasyid, M. ; Tönjes, A.* ; Kovacs, P.* ; Lehtimäki, T.* ; Raitakari, O.* ; Kähönen, M.* ; Gylling, H.* ; Baber, R.* ; Isermann, B.* ; Stumvoll, M.* ; Loeffler, M.* ; März, 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. 13:143 (2022)

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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.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

ISSN (print) / ISBN 2041-1723

e-ISSN 2041-1723

Journal Nature Communications

Quellenangaben Volume: 13, Issue: 1, Article Number: 143

Publisher Nature Publishing Group

Publishing Place London

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Epidemiology II (EPI2)
Institute of Genetic Epidemiology (IGE)

Grants Münchner Zentrum für Gesundheitswissenschaften, Ludwig-Maximilians-Universität München
Turun Yliopistollinen Keskussairaala
European Regional Development Fund
Paavo Nurmen Säätiö
Tampereen Tuberkuloosisäätiö
Sigrid Juséliuksen Säätiö
Sydäntutkimussäätiö
Emil Aaltosen Säätiö
Signe ja Ane Gyllenbergin Säätiö
Juho Vainion Säätiö
Suomen Kulttuurirahasto
Bundesministerium für Bildung und Forschung
EC | European Research Council (ERC)
European Commission
Yrjö Jahnssonin Säätiö
Pfizer
Tampere University Hospital Supporting Foundation
Nationales Genomforschungsnetz (NGFN)
MONICA
Helmholtz Zentrum München–National Research Center for Environmental Health
German National Genome Research Network
German Federal Ministry of Education, Science, Research and Technology
German Diabetes Association
German Center for Diabetes Research
Finnish Society of Clinical Chemistry
Diabetes Research Foundation of Finnish Diabetes Association
Diabetes Hilfs-und Forschungsfonds Deutschland
Projekt DEAL