An epigenome-wide association study of metabolic syndrome and its components

The role of metabolic syndrome (MetS) as a preceding metabolic state for type 2 diabetes and cardiovascular disease is widely recognised. To accumulate knowledge of the pathological mechanisms behind the condition at the methylation level, we conducted an epigenome-wide association study (EWAS) of M...

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Vydané v:Scientific reports Ročník 10; číslo 1; s. 20567 - 12
Hlavní autori: Nuotio, Marja-Liisa, Pervjakova, Natalia, Joensuu, Anni, Karhunen, Ville, Hiekkalinna, Tero, Milani, Lili, Kettunen, Johannes, Järvelin, Marjo-Riitta, Jousilahti, Pekka, Metspalu, Andres, Salomaa, Veikko, Kristiansson, Kati, Perola, Markus
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: London Nature Publishing Group UK 25.11.2020
Nature Publishing Group
Nature Portfolio
Predmet:
631/208/176/1988
692/308/2056
Adult
Aged
ATP Binding Cassette Transporter, Subfamily G, Member 1 - genetics
Cardiovascular diseases
Carrier Proteins - genetics
Chromosome 1
Chromosome 21
Diabetes
Diabetes mellitus (non-insulin dependent)
Diabetes Mellitus, Type 2 - genetics
DNA methylation
DNA Methylation - genetics
Epigenesis, Genetic - genetics
Epigenome - genetics
Epigenomics - methods
Female
Finland - epidemiology
Genome - genetics
Genome-Wide Association Study - methods
Genomes
Glucose
Glucose - metabolism
High density lipoprotein
Humanities and Social Sciences
Humans
Lipid metabolism
Lipid Metabolism - genetics
Lipids - genetics
Male
Metabolic disorders
Metabolic syndrome
Metabolic Syndrome - genetics
Metabolic Syndrome - metabolism
Methylation
Middle Aged
multidisciplinary
Polymorphism, Single Nucleotide - genetics
Science
Science (multidisciplinary)
Triglycerides
White People - genetics
Finland
ISSN:2045-2322, 2045-2322
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Abstract The role of metabolic syndrome (MetS) as a preceding metabolic state for type 2 diabetes and cardiovascular disease is widely recognised. To accumulate knowledge of the pathological mechanisms behind the condition at the methylation level, we conducted an epigenome-wide association study (EWAS) of MetS and its components, testing 1187 individuals of European ancestry for approximately 470 000 methylation sites throughout the genome. Methylation site cg19693031 in gene TXNIP —previously associated with type 2 diabetes, glucose and lipid metabolism, associated with fasting glucose level ( P  = 1.80 × 10 −8 ). Cg06500161 in gene ABCG1 associated both with serum triglycerides ( P  = 5.36 × 10 −9 ) and waist circumference ( P  = 5.21 × 10 −9 ). The previously identified type 2 diabetes–associated locus cg08309687 in chromosome 21 associated with waist circumference for the first time ( P  = 2.24 × 10 −7 ). Furthermore, a novel HDL association with cg17901584 in chromosome 1 was identified ( P  = 7.81 × 10 −8 ). Our study supports previous genetic studies of MetS, finding that lipid metabolism plays a key role in pathology of the syndrome. We provide evidence regarding a close interplay with glucose metabolism. Finally, we suggest that in attempts to identify methylation loci linking separate MetS components, cg19693031 appears to represent a strong candidate.
AbstractList The role of metabolic syndrome (MetS) as a preceding metabolic state for type 2 diabetes and cardiovascular disease is widely recognised. To accumulate knowledge of the pathological mechanisms behind the condition at the methylation level, we conducted an epigenome-wide association study (EWAS) of MetS and its components, testing 1187 individuals of European ancestry for approximately 470 000 methylation sites throughout the genome. Methylation site cg19693031 in gene TXNIP —previously associated with type 2 diabetes, glucose and lipid metabolism, associated with fasting glucose level (P = 1.80 × 10−8). Cg06500161 in gene ABCG1 associated both with serum triglycerides (P = 5.36 × 10−9) and waist circumference (P = 5.21 × 10−9). The previously identified type 2 diabetes–associated locus cg08309687 in chromosome 21 associated with waist circumference for the first time (P = 2.24 × 10−7). Furthermore, a novel HDL association with cg17901584 in chromosome 1 was identified (P = 7.81 × 10−8). Our study supports previous genetic studies of MetS, finding that lipid metabolism plays a key role in pathology of the syndrome. We provide evidence regarding a close interplay with glucose metabolism. Finally, we suggest that in attempts to identify methylation loci linking separate MetS components, cg19693031 appears to represent a strong candidate.
The role of metabolic syndrome (MetS) as a preceding metabolic state for type 2 diabetes and cardiovascular disease is widely recognised. To accumulate knowledge of the pathological mechanisms behind the condition at the methylation level, we conducted an epigenome-wide association study (EWAS) of MetS and its components, testing 1187 individuals of European ancestry for approximately 470 000 methylation sites throughout the genome. Methylation site cg19693031 in gene TXNIP —previously associated with type 2 diabetes, glucose and lipid metabolism, associated with fasting glucose level ( P  = 1.80 × 10 −8 ). Cg06500161 in gene ABCG1 associated both with serum triglycerides ( P  = 5.36 × 10 −9 ) and waist circumference ( P  = 5.21 × 10 −9 ). The previously identified type 2 diabetes–associated locus cg08309687 in chromosome 21 associated with waist circumference for the first time ( P  = 2.24 × 10 −7 ). Furthermore, a novel HDL association with cg17901584 in chromosome 1 was identified ( P  = 7.81 × 10 −8 ). Our study supports previous genetic studies of MetS, finding that lipid metabolism plays a key role in pathology of the syndrome. We provide evidence regarding a close interplay with glucose metabolism. Finally, we suggest that in attempts to identify methylation loci linking separate MetS components, cg19693031 appears to represent a strong candidate.
The role of metabolic syndrome (MetS) as a preceding metabolic state for type 2 diabetes and cardiovascular disease is widely recognised. To accumulate knowledge of the pathological mechanisms behind the condition at the methylation level, we conducted an epigenome-wide association study (EWAS) of MetS and its components, testing 1187 individuals of European ancestry for approximately 470 000 methylation sites throughout the genome. Methylation site cg19693031 in gene TXNIP -previously associated with type 2 diabetes, glucose and lipid metabolism, associated with fasting glucose level (P = 1.80 × 10-8). Cg06500161 in gene ABCG1 associated both with serum triglycerides (P = 5.36 × 10-9) and waist circumference (P = 5.21 × 10-9). The previously identified type 2 diabetes-associated locus cg08309687 in chromosome 21 associated with waist circumference for the first time (P = 2.24 × 10-7). Furthermore, a novel HDL association with cg17901584 in chromosome 1 was identified (P = 7.81 × 10-8). Our study supports previous genetic studies of MetS, finding that lipid metabolism plays a key role in pathology of the syndrome. We provide evidence regarding a close interplay with glucose metabolism. Finally, we suggest that in attempts to identify methylation loci linking separate MetS components, cg19693031 appears to represent a strong candidate.The role of metabolic syndrome (MetS) as a preceding metabolic state for type 2 diabetes and cardiovascular disease is widely recognised. To accumulate knowledge of the pathological mechanisms behind the condition at the methylation level, we conducted an epigenome-wide association study (EWAS) of MetS and its components, testing 1187 individuals of European ancestry for approximately 470 000 methylation sites throughout the genome. Methylation site cg19693031 in gene TXNIP -previously associated with type 2 diabetes, glucose and lipid metabolism, associated with fasting glucose level (P = 1.80 × 10-8). Cg06500161 in gene ABCG1 associated both with serum triglycerides (P = 5.36 × 10-9) and waist circumference (P = 5.21 × 10-9). The previously identified type 2 diabetes-associated locus cg08309687 in chromosome 21 associated with waist circumference for the first time (P = 2.24 × 10-7). Furthermore, a novel HDL association with cg17901584 in chromosome 1 was identified (P = 7.81 × 10-8). Our study supports previous genetic studies of MetS, finding that lipid metabolism plays a key role in pathology of the syndrome. We provide evidence regarding a close interplay with glucose metabolism. Finally, we suggest that in attempts to identify methylation loci linking separate MetS components, cg19693031 appears to represent a strong candidate.
The role of metabolic syndrome (MetS) as a preceding metabolic state for type 2 diabetes and cardiovascular disease is widely recognised. To accumulate knowledge of the pathological mechanisms behind the condition at the methylation level, we conducted an epigenome-wide association study (EWAS) of MetS and its components, testing 1187 individuals of European ancestry for approximately 470 000 methylation sites throughout the genome. Methylation site cg19693031 in gene TXNIP -previously associated with type 2 diabetes, glucose and lipid metabolism, associated with fasting glucose level (P = 1.80 × 10 ). Cg06500161 in gene ABCG1 associated both with serum triglycerides (P = 5.36 × 10 ) and waist circumference (P = 5.21 × 10 ). The previously identified type 2 diabetes-associated locus cg08309687 in chromosome 21 associated with waist circumference for the first time (P = 2.24 × 10 ). Furthermore, a novel HDL association with cg17901584 in chromosome 1 was identified (P = 7.81 × 10 ). Our study supports previous genetic studies of MetS, finding that lipid metabolism plays a key role in pathology of the syndrome. We provide evidence regarding a close interplay with glucose metabolism. Finally, we suggest that in attempts to identify methylation loci linking separate MetS components, cg19693031 appears to represent a strong candidate.
Abstract The role of metabolic syndrome (MetS) as a preceding metabolic state for type 2 diabetes and cardiovascular disease is widely recognised. To accumulate knowledge of the pathological mechanisms behind the condition at the methylation level, we conducted an epigenome-wide association study (EWAS) of MetS and its components, testing 1187 individuals of European ancestry for approximately 470 000 methylation sites throughout the genome. Methylation site cg19693031 in gene TXNIP —previously associated with type 2 diabetes, glucose and lipid metabolism, associated with fasting glucose level (P = 1.80 × 10−8). Cg06500161 in gene ABCG1 associated both with serum triglycerides (P = 5.36 × 10−9) and waist circumference (P = 5.21 × 10−9). The previously identified type 2 diabetes–associated locus cg08309687 in chromosome 21 associated with waist circumference for the first time (P = 2.24 × 10−7). Furthermore, a novel HDL association with cg17901584 in chromosome 1 was identified (P = 7.81 × 10−8). Our study supports previous genetic studies of MetS, finding that lipid metabolism plays a key role in pathology of the syndrome. We provide evidence regarding a close interplay with glucose metabolism. Finally, we suggest that in attempts to identify methylation loci linking separate MetS components, cg19693031 appears to represent a strong candidate.
The role of metabolic syndrome (MetS) as a preceding metabolic state for type 2 diabetes and cardiovascular disease is widely recognised. To accumulate knowledge of the pathological mechanisms behind the condition at the methylation level, we conducted an epigenome-wide association study (EWAS) of MetS and its components, testing 1187 individuals of European ancestry for approximately 470 000 methylation sites throughout the genome. Methylation site cg19693031 in gene TXNIP —previously associated with type 2 diabetes, glucose and lipid metabolism, associated with fasting glucose level (P = 1.80 × 10−8). Cg06500161 in gene ABCG1 associated both with serum triglycerides (P = 5.36 × 10−9) and waist circumference (P = 5.21 × 10−9). The previously identified type 2 diabetes–associated locus cg08309687 in chromosome 21 associated with waist circumference for the first time (P = 2.24 × 10−7). Furthermore, a novel HDL association with cg17901584 in chromosome 1 was identified (P = 7.81 × 10−8). Our study supports previous genetic studies of MetS, finding that lipid metabolism plays a key role in pathology of the syndrome. We provide evidence regarding a close interplay with glucose metabolism. Finally, we suggest that in attempts to identify methylation loci linking separate MetS components, cg19693031 appears to represent a strong candidate.
ArticleNumber 20567
Author Järvelin, Marjo-Riitta
Joensuu, Anni
Jousilahti, Pekka
Milani, Lili
Pervjakova, Natalia
Kristiansson, Kati
Nuotio, Marja-Liisa
Karhunen, Ville
Kettunen, Johannes
Perola, Markus
Hiekkalinna, Tero
Salomaa, Veikko
Metspalu, Andres
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  organization: Center for Life Course Health Research, University of Oulu, Biocenter Oulu, University of Oulu, Unit of Primary Health Care, Oulu University Hospital, Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London
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  organization: Genomics and Biobank Unit, Department of Public Health Solutions, National Institute for Health and Welfare, Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki
BackLink https://www.ncbi.nlm.nih.gov/pubmed/33239708$$D View this record in MEDLINE/PubMed
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– volume: 10
  start-page: 49
  year: 2018
  ident: 77506_CR10
  publication-title: ClinEpigenet.
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Snippet The role of metabolic syndrome (MetS) as a preceding metabolic state for type 2 diabetes and cardiovascular disease is widely recognised. To accumulate...
Abstract The role of metabolic syndrome (MetS) as a preceding metabolic state for type 2 diabetes and cardiovascular disease is widely recognised. To...
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SubjectTerms 631/208/176/1988
692/308/2056
Adult
Aged
ATP Binding Cassette Transporter, Subfamily G, Member 1 - genetics
Cardiovascular diseases
Carrier Proteins - genetics
Chromosome 1
Chromosome 21
Diabetes
Diabetes mellitus (non-insulin dependent)
Diabetes Mellitus, Type 2 - genetics
DNA methylation
DNA Methylation - genetics
Epigenesis, Genetic - genetics
Epigenome - genetics
Epigenomics - methods
Female
Finland - epidemiology
Genome - genetics
Genome-Wide Association Study - methods
Genomes
Glucose
Glucose - metabolism
High density lipoprotein
Humanities and Social Sciences
Humans
Lipid metabolism
Lipid Metabolism - genetics
Lipids - genetics
Male
Metabolic disorders
Metabolic syndrome
Metabolic Syndrome - genetics
Metabolic Syndrome - metabolism
Methylation
Middle Aged
multidisciplinary
Polymorphism, Single Nucleotide - genetics
Science
Science (multidisciplinary)
Triglycerides
White People - genetics
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Title An epigenome-wide association study of metabolic syndrome and its components
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