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SNPs were selected based on functional effects and gene coverage, and assays were completed on the Illumina Goldengate platform. Age-, smoking-, and nutrient-adjusted genotype--phenotype associations were estimated in regression models.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Using a nominal P \u2264 0.005 threshold for statistical significance, 20 SNPs were associated with plasma homocysteine, 8 with Alu methylation, and 1 with LINE-1 methylation. Using a more stringent false discovery rate threshold, SNPs in<jats:italic>FTCD<\/jats:italic>,<jats:italic>SLC19A1<\/jats:italic>, and<jats:italic>SLC19A3<\/jats:italic>genes remained associated with plasma homocysteine. Gene by vitamin B-6 interactions were identified for both Alu and LINE-1 methylation, and epistatic interactions with the<jats:italic>MTHFR<\/jats:italic>rs1801133 SNP were identified for the plasma homocysteine phenotype. Pleiotropy involving the<jats:italic>MTHFD1L<\/jats:italic>and<jats:italic>SARDH<\/jats:italic>genes for both plasma homocysteine and Alu methylation phenotypes was identified.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>No single gene was associated with all three phenotypes, and the set of the most statistically significant SNPs predictive of homocysteine or Alu or LINE-1 methylation was unique to each phenotype. Genetic variation in folate-mediated one-carbon metabolism, other than the well-known effects of the<jats:italic>MTHFR<\/jats:italic>c.665C&gt;T (known as c.677 C&gt;T, rs1801133, p.Ala222Val), is predictive of cardiovascular disease biomarkers.<\/jats:p><\/jats:sec>","DOI":"10.1186\/1471-2350-12-150","type":"journal-article","created":{"date-parts":[[2011,11,22]],"date-time":"2011-11-22T07:28:00Z","timestamp":1321946880000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Folate network genetic variation, plasma homocysteine, and global genomic methylation content: a genetic association study"],"prefix":"10.1186","volume":"12","author":[{"given":"Susan M","family":"Wernimont","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew G","family":"Clark","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick J","family":"Stover","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin T","family":"Wells","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Augusto A","family":"Litonjua","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott T","family":"Weiss","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J Michael","family":"Gaziano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katherine L","family":"Tucker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Baccarelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joel","family":"Schwartz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valentina","family":"Bollati","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricia A","family":"Cassano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2011,11,21]]},"reference":[{"key":"891_CR1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/S0083-6729(08)00401-9","volume":"79","author":"JT Fox","year":"2008","unstructured":"Fox JT, Stover PJ: Folate-mediated one-carbon metabolism. 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