{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T23:24:30Z","timestamp":1789946670191,"version":"4.0.1"},"reference-count":60,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2019,5,21]]},"abstract":"\n Background<\/jats:title>\n \n Recent studies have revealed sexually dimorphic associations between the carbamoyl\u2010phosphate synthase 1 locus, intermediates of the metabolic pathway leading from choline to urea, and risk of coronary artery disease (\n CAD<\/jats:styled-content>\n ) in women. Based on evidence from the literature, the atheroprotective association with carbamoyl\u2010phosphate synthase 1 could be mediated by the strong genetic effect of this locus on increased circulating glycine levels.\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n We sought to identify additional genetic determinants of circulating glycine levels by carrying out a meta\u2010analysis of genome\u2010wide association study data in up to 30\u00a0118 subjects of European ancestry. Mendelian randomization and other analytical approaches were used to determine whether glycine\u2010associated variants were associated with\n CAD<\/jats:styled-content>\n 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 (\n \n ACADM<\/jats:styled-content>\n <\/jats:italic>\n ,\n \n PHGDH<\/jats:styled-content>\n <\/jats:italic>\n ,\n \n COX<\/jats:styled-content>\n 18\u2010\n ADAMTS<\/jats:styled-content>\n 3\n <\/jats:italic>\n ,\n \n PSPH<\/jats:styled-content>\n <\/jats:italic>\n ,\n \n TRIB<\/jats:styled-content>\n 1\n <\/jats:italic>\n ,\n \n PTPRD<\/jats:styled-content>\n <\/jats:italic>\n , and\n \n ABO<\/jats:styled-content>\n <\/jats:italic>\n ). Glycine\u2010raising alleles at several loci individually exhibited directionally consistent associations with decreased risk of\n CAD<\/jats:styled-content>\n . However, these effects could not be attributed directly to glycine because of associations with other\n CAD<\/jats:styled-content>\n \u2010related 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\n CAD<\/jats:styled-content>\n or blood pressure, lipid levels, and obesity\u2010related traits.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n 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\n CAD<\/jats:styled-content>\n in humans.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.119.011922","type":"journal-article","created":{"date-parts":[[2019,5,9]],"date-time":"2019-05-09T09:14:20Z","timestamp":1557393260000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":24,"title":["Genetic Determinants of Circulating Glycine Levels and Risk of Coronary Artery Disease"],"prefix":"10.1161","volume":"8","author":[{"given":"Qiong","family":"Jia","sequence":"first","affiliation":[{"name":"Department of Preventive Medicine Keck School of Medicine, University of Southern California Los Angeles CA"},{"name":"Department of Biochemistry & Molecular Medicine Keck School of Medicine, University of Southern California Los Angeles CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine Keck School of Medicine, University of Southern California Los Angeles CA"},{"name":"Department of Biochemistry & Molecular Medicine Keck School of Medicine, University of Southern California Los Angeles CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pin","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine Keck School of Medicine, University of Southern California Los Angeles 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