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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Veröffentlicht in:	Scientific reports Jg. 10; H. 1; S. 20567 - 12
Hauptverfasser:	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
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	London Nature Publishing Group UK 25.11.2020 Nature Publishing Group Nature Portfolio
Schlagworte:	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
Online-Zugang:	Volltext
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Zusammenfassung:	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.
Bibliographie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	2045-2322 2045-2322
DOI:	10.1038/s41598-020-77506-z