Genome-wide association study identifies common variants associated with circulating vitamin E levels

Jacqueline M. Major, Kai Yu, William Wheeler, Hong Zhang, Marilyn C. Cornelis, Margaret E. Wright, Meredith Yeager, Kirk Snyder, Stephanie J. Weinstein, Alison Mondul, Heather Eliassen, Mark Purdue, Aditi Hazra, Catherine A. McCarty, Sara Hendrickson, Jarmo Virtamo, David Hunter, Stephen Chanock, Peter Kraft, Demetrius Albanes

Research output: Contribution to journalArticle

Abstract

In genome-wide association studies (GWAS) of common genetic variants associated with circulating alphaand gamma-tocopherol concentrations in two adult cohorts comprising 5006 men of European descent, we observed three loci associated with alpha-tocopherol levels, two novel single-nucleotide polymorphisms (SNPs), rs2108622 on 19pter-p13.11 (P = 1.7 × 10 -8) and rs11057830 on 12q24.31 (P = 2.0 × 10 -8) and confirmed a previously reported locus marked by rs964184 on 11q23.3 (P = 2.7 × 10 -10). The three SNPs have been reported to be associated with lipid metabolism and/or regulation. We replicated these findings in a combined meta-analysis with two independent samples, P = 7.8 × 10 -12 (rs964184 on 11q23.3 near BUD13, ZNF259 and APOA1/C3/A4/A5), P = 1.4 × 10 -10 (rs2108622 on 19pter-p13.11 near CYP4F2) and P = 8.2 × 10 -9 (rs11057830 on 12q24.31 near SCARB1). Combined, these SNPs explain 1.7% of the residual variance in log alpha-tocopherol levels. In one of the two male GWAS cohorts (n = 992), no SNPs were significantly associated with gamma-tocopherol concentrations after including data from the replication sample for 71 independent SNPs with P < 1 × 10 -4 identified. Published by Oxford University Press 2011.

Original languageEnglish (US)
Article numberddr296
Pages (from-to)3876-3883
Number of pages8
JournalHuman molecular genetics
Volume20
Issue number19
DOIs
StatePublished - Oct 2011

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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    Major, J. M., Yu, K., Wheeler, W., Zhang, H., Cornelis, M. C., Wright, M. E., Yeager, M., Snyder, K., Weinstein, S. J., Mondul, A., Eliassen, H., Purdue, M., Hazra, A., McCarty, C. A., Hendrickson, S., Virtamo, J., Hunter, D., Chanock, S., Kraft, P., & Albanes, D. (2011). Genome-wide association study identifies common variants associated with circulating vitamin E levels. Human molecular genetics, 20(19), 3876-3883. [ddr296]. https://doi.org/10.1093/hmg/ddr296