Journal
NATURE COMMUNICATIONS
Volume 13, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41467-021-27706-6
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Funding
- German Federal Ministry of Education, Science, Research and Technology
- State of Bavaria
- German National Genome Research Network (NGFN)
- Munich Center of Health Sciences (MC Health), LMUinnovativ
- Leipzig Research Center for Civilization Diseases (LIFE)
- European Union
- European Regional Development Fund (ERDF)
- Free State of Saxony
- Collaborative Research Center - German Research Foundation [CRC 1052, SPP 1629 TO 718/2]
- German Diabetes Association
- DHFD (Diabetes Hilfs- und Forschungsfonds Deutschland)
- German Center for Diabetes Research
- European Union [201668, 305739]
- Academy of Finland [322098, 286284, 134309, 126925, 121584, 124282, 129378, 117787, 41071]
- Social Insurance Institution of Finland
- Expert Responsibility area of Kuopio University Hospital [X51001]
- Juho Vainio Foundation
- Paavo Nurmi Foundation
- Finnish Foundation for Cardiovascular Research
- Finnish Cultural Foundation
- Sigrid Juselius Foundation
- Tampere Tuberculosis Foundation
- Emil Aaltonen Foundation
- Yrjo Jahnsson Foundation
- Signe and Ane Gyllenberg Foundation
- Diabetes Research Foundation of Finnish Diabetes Association
- EU Horizon 2020 [755320, 848146]
- European Research Council [742927]
- Tampere University Hospital Supporting Foundation
- Finnish Society of Clinical Chemistry
- German Federal Ministry of Education and Research (BMBF) [01ZX1906B]
- Expert Responsibility area of Tampere University Hospital [X51001]
- Expert Responsibility area of Turku University Hospital [X51001]
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Phytosterol serum concentrations are genetically controlled and have a controversial relationship with coronary artery disease. Genome-wide analyses identify multiple genetic loci associated with phytosterol traits and demonstrate a causal relationship between sitosterol concentrations and coronary artery disease.
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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