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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Published inNature communications Vol. 13; no. 1; pp. 143 - 12
Main 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
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 10.01.2022
Nature Publishing Group
Nature Portfolio
Subjects
45/43
631/208/205/2138
692/308/2056
692/4017
692/699/75
ABO Blood-Group System - blood
ABO Blood-Group System - genetics
Adult
Apolipoprotein E
Apolipoproteins E - blood
Apolipoproteins E - genetics
Arteriosclerosis
Atherosclerosis
ATP Binding Cassette Transporter, Subfamily G, Member 5 - blood
ATP Binding Cassette Transporter, Subfamily G, Member 5 - genetics
ATP Binding Cassette Transporter, Subfamily G, Member 8 - blood
ATP Binding Cassette Transporter, Subfamily G, Member 8 - genetics
Cardiovascular disease
Cholesterol
Cholesterol - blood
Coronary artery
Coronary artery disease
Coronary Artery Disease - blood
Coronary Artery Disease - genetics
Coronary Artery Disease - pathology
Coronary vessels
Esterification
Female
Gene Expression Regulation
Gene loci
Genetic control
Genetic Loci
Genetic Predisposition to Disease
Genome-Wide Association Study
Genomes
Heart diseases
Heterogeneity
Homology
Humanities and Social Sciences
Humans
Hydroxymethylglutaryl CoA Reductases - blood
Hydroxymethylglutaryl CoA Reductases - genetics
Lipase - blood
Lipase - genetics
Lipid Metabolism - genetics
Lipoproteins - blood
Lipoproteins - genetics
Male
Membrane Transport Proteins - blood
Membrane Transport Proteins - genetics
Mendelian Randomization Analysis
Meta-analysis
multidisciplinary
Multifactorial Inheritance
Phytosterols
Phytosterols - blood
Polygenic inheritance
Polymorphism, Single Nucleotide
Scavenger Receptors, Class B - blood
Scavenger Receptors, Class B - genetics
Science
Science (multidisciplinary)
Single-nucleotide polymorphism
Vein & artery diseases
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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 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. Physterols are cholesterol homologs derived from plants, which are found in humans through consumption of plant products. Here the authors have performed a genome-wide meta-analysis of 32 serum phytosterol traits, with evidence suggesting causality between sitosterol and coronary artery disease.
AbstractList 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.
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. Physterols are cholesterol homologs derived from plants, which are found in humans through consumption of plant products. Here the authors have performed a genome-wide meta-analysis of 32 serum phytosterol traits, with evidence suggesting causality between sitosterol 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 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.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.
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.Physterols are cholesterol homologs derived from plants, which are found in humans through consumption of plant products. Here the authors have performed a genome-wide meta-analysis of 32 serum phytosterol traits, with evidence suggesting causality between sitosterol and coronary artery disease.
Physterols are cholesterol homologs derived from plants, which are found in humans through consumption of plant products. Here the authors have performed a genome-wide meta-analysis of 32 serum phytosterol traits, with evidence suggesting causality between sitosterol 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 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.
ArticleNumber 143
Author Baber, Ronny
Thiery, Joachim
Gross, Arnd
Kähönen, Mika
Tönjes, Anke
Mishra, Pashupati Prasad
Kirsten, Holger
Meitinger, Thomas
März, Winfried
Gieger, Christian
Delgado, Graciela E.
Gylling, Helena
Isermann, Berend
Scholz, Markus
Raitakari, Olli
Peters, Annette
Müller-Nurasyid, Martina
Ceglarek, Uta
Horn, Katrin
Pott, Janne
Kovacs, Peter
Lehtimäki, Terho
Kleber, Marcus E.
Stumvoll, Michael
Loeffler, Markus
Teupser, Daniel
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/35013273$$D View this record in MEDLINE/PubMed
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– reference: 35217655 - Nat Commun. 2022 Feb 25;13(1):1122
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Snippet Phytosterol serum concentrations are under tight genetic control. The relationship between phytosterols and coronary artery disease (CAD) is controversially...
Physterols are cholesterol homologs derived from plants, which are found in humans through consumption of plant products. Here the authors have performed a...
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SubjectTerms 45/43
631/208/205/2138
692/308/2056
692/4017
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ABO Blood-Group System - blood
ABO Blood-Group System - genetics
Adult
Apolipoprotein E
Apolipoproteins E - blood
Apolipoproteins E - genetics
Arteriosclerosis
Atherosclerosis
ATP Binding Cassette Transporter, Subfamily G, Member 5 - blood
ATP Binding Cassette Transporter, Subfamily G, Member 5 - genetics
ATP Binding Cassette Transporter, Subfamily G, Member 8 - blood
ATP Binding Cassette Transporter, Subfamily G, Member 8 - genetics
Cardiovascular disease
Cholesterol
Cholesterol - blood
Coronary artery
Coronary artery disease
Coronary Artery Disease - blood
Coronary Artery Disease - genetics
Coronary Artery Disease - pathology
Coronary vessels
Esterification
Female
Gene Expression Regulation
Gene loci
Genetic control
Genetic Loci
Genetic Predisposition to Disease
Genome-Wide Association Study
Genomes
Heart diseases
Heterogeneity
Homology
Humanities and Social Sciences
Humans
Hydroxymethylglutaryl CoA Reductases - blood
Hydroxymethylglutaryl CoA Reductases - genetics
Lipase - blood
Lipase - genetics
Lipid Metabolism - genetics
Lipoproteins - blood
Lipoproteins - genetics
Male
Membrane Transport Proteins - blood
Membrane Transport Proteins - genetics
Mendelian Randomization Analysis
Meta-analysis
multidisciplinary
Multifactorial Inheritance
Phytosterols
Phytosterols - blood
Polygenic inheritance
Polymorphism, Single Nucleotide
Scavenger Receptors, Class B - blood
Scavenger Receptors, Class B - genetics
Science
Science (multidisciplinary)
Single-nucleotide polymorphism
Vein & artery diseases
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Title Genome-wide meta-analysis of phytosterols reveals five novel loci and a detrimental effect on coronary atherosclerosis
URI https://link.springer.com/article/10.1038/s41467-021-27706-6
https://www.ncbi.nlm.nih.gov/pubmed/35013273
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Volume 13
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