Genetic Determinants of Circulating Glycine Levels and Risk of Coronary Artery Disease

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Jia , Q , Han , Y , Huang , P , Woodward , N C , Gukasyan , J , Kettunen , J , Ala-Korpela , M , Anufrieva , O , Wang , Q , Perola , M , Raitakari , O , Lehtimaki , T , Viikari , J , Jarvelin , M-R , Boehnke , M , Laakso , M , Mohlke , K L , Fiehn , O , Wang , Z , Tang , W H W , Hazen , S L , Hartiala , J A & Allayee , H 2019 , ' Genetic Determinants of Circulating Glycine Levels and Risk of Coronary Artery Disease ' , Journal of the American Heart Association , vol. 8 , no. 10 , 011922 . https://doi.org/10.1161/JAHA.119.011922

Title: Genetic Determinants of Circulating Glycine Levels and Risk of Coronary Artery Disease
Author: Jia, Qiong; Han, Yi; Huang, Pin; Woodward, Nicholas C.; Gukasyan, Janet; Kettunen, Johannes; Ala-Korpela, Mika; Anufrieva, Olga; Wang, Qin; Perola, Markus; Raitakari, Olli; Lehtimaki, Terho; Viikari, Jorma; Jarvelin, Marjo-Riitta; Boehnke, Michael; Laakso, Markku; Mohlke, Karen L.; Fiehn, Oliver; Wang, Zeneng; Tang, W. H. Wilson; Hazen, Stanley L.; Hartiala, Jaana A.; Allayee, Hooman
Contributor: University of Helsinki, Institute for Molecular Medicine Finland
Date: 2019-05-21
Number of pages: 27
Belongs to series: Journal of the American Heart Association
ISSN: 2047-9980
URI: http://hdl.handle.net/10138/311673
Abstract: Background-Recent studies have revealed sexually dimorphic associations between the carbamoyl-phosphate synthase 1 locus, intermediates of the metabolic pathway leading from choline to urea, and risk of coronary artery disease (CAD) in women. Based on evidence from the literature, the atheroprotective association with carbamoyl-phosphate synthase 1 could be mediated by the strong genetic effect of this locus on increased circulating glycine levels. Methods and Results-We sought to identify additional genetic determinants of circulating glycine levels by carrying out a metaanalysis of genome-wide association study data in up to 30 118 subjects of European ancestry. Mendelian randomization and other analytical approaches were used to determine whether glycine-associated variants were associated with CAD and traditional risk factors. Twelve loci were significantly associated with circulating glycine levels, 7 of which were not previously known to be involved in glycine metabolism (ACADM, PHGDH, COX1 8-ADAMTS3, PSPH, TRIB 1 , PTPRD, and ABO). Glycine-raising alleles at several loci individually exhibited directionally consistent associations with decreased risk of CAD. However, these effects could not be attributed directly to glycine because of associations with other CAD-related traits. By comparison, genetic models that only included the 2 variants directly involved in glycine degradation and for which there were no other pleiotropic associations were not associated with risk of CAD or blood pressure, lipid levels, and obesity-related traits. Conclusions-These results provide additional insight into the genetic architecture of glycine metabolism, but do not yield conclusive evidence for a causal relationship between circulating levels of this amino acid and risk of CAD in humans.
Subject: causality
coronary artery disease
genome-wide association study
glycine
Mendelian randomization
meta-analysis
GENOME-WIDE ASSOCIATION
3-PHOSPHOGLYCERATE DEHYDROGENASE-DEFICIENCY
PLASMA HOMOCYSTEINE
CARDIOVASCULAR RISK
RARE VARIANTS
LOCI
METABOLISM
WOMEN
CPS1
PHOSPHATIDYLCHOLINE
3121 Internal medicine
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