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Common variants of FUT2 are associated with plasma vitamin B12 levels

Abstract

We identified a strong association (P = 5.36 × 10−17) between rs492602 in FUT2 and plasma vitamin B12 levels in a genome-wide scan (n = 1,658) and an independent replication sample (n = 1,059) from the Nurses' Health Study. Women homozygous for the rs492602[G] allele had higher B12 levels. This allele is in strong linkage disequilibrium with the FUT2 nonsecretor variant encoding W143X, suggesting a plausible mechanism for altered B12 absorption and plasma levels.

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Figure 1: LD structure of chromosome 19.

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Acknowledgements

We thank H. Ranu, C. Chen and the staff at the Core Genotyping Facility at the National Cancer Institute for their expertise. This research is supported by the National Institutes of Health Research Grants U54 CA100971, P01 CA87969, P01 CA55075, U01 CA098233, R01 CA 065725 and CA070817. A.H. is supported in part by training grant NIH T-32 CA 09001-30.

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Contributions

This study is a joint effort of the Nurses' Health Study investigators (A.H., P.K., E.L.G. and D.J.H.) and Cancer Genetics Markers of Susceptibility study investigators (G.T., R.N.H., S.J.C. and D.J.H.). A.H. and D.J.H. designed the study; J.S. measured the plasma vitamin B12 and homocysteine levels; A.H. performed the analyses; P.K. supervised the statistical analyses; A.H. wrote the manuscript and prepared the tables, figures and supplementary material, with input from all co-authors.

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Correspondence to David J Hunter.

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Supplementary Methods, Supplementary Figures 1–3, Supplementary Tables 1 and 2 (PDF 328 kb)

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Hazra, A., Kraft, P., Selhub, J. et al. Common variants of FUT2 are associated with plasma vitamin B12 levels. Nat Genet 40, 1160–1162 (2008). https://doi.org/10.1038/ng.210

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