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

doi:10.1093/hmg/ddr296

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

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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 language	English (US)
Article number	ddr296
Pages (from-to)	3876-3883
Number of pages	8
Journal	Human molecular genetics
Volume	20
Issue number	19
DOIs	https://doi.org/10.1093/hmg/ddr296
State	Published - Oct 2011

Bibliographical note

Funding Information:
This work was supported in part by the Intramural Research Program of the National Institutes of Health and the National Cancer Institute. Additionally, the research was supported by Public Health Service contracts (N01-CN-45165, N01-RC-45035, N01-RC-37004 and HHSN261201000006C) from the National Cancer Institute, Department of Health and Human Services. S.H. is supported in part by training grant NIH 5 T32 CA09001-35. H.E. is supported in part by grant NIH R01 CA131218.

Funding Information:
Funding to pay the Open Access publication charges for this article was provided by the Intramural Program of the US National Cancer Institute, National Institutes of Health, Department of Health and Human Services.

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10.1093/hmg/ddr296

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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. Article ddr296. https://doi.org/10.1093/hmg/ddr296

Major, JM, Yu, K, Wheeler, W, Zhang, H, Cornelis, MC, Wright, ME, Yeager, M, Snyder, K, Weinstein, SJ, Mondul, A, Eliassen, H, Purdue, M, Hazra, A, McCarty, CA, 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, vol. 20, no. 19, ddr296, pp. 3876-3883. https://doi.org/10.1093/hmg/ddr296

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title = "Genome-wide association study identifies common variants associated with circulating vitamin E levels",

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.",

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

note = "Funding Information: This work was supported in part by the Intramural Research Program of the National Institutes of Health and the National Cancer Institute. Additionally, the research was supported by Public Health Service contracts (N01-CN-45165, N01-RC-45035, N01-RC-37004 and HHSN261201000006C) from the National Cancer Institute, Department of Health and Human Services. S.H. is supported in part by training grant NIH 5 T32 CA09001-35. H.E. is supported in part by grant NIH R01 CA131218. Funding Information: Funding to pay the Open Access publication charges for this article was provided by the Intramural Program of the US National Cancer Institute, National Institutes of Health, Department of Health and Human Services.",

year = "2011",

month = oct,

doi = "10.1093/hmg/ddr296",

language = "English (US)",

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AU - Major, Jacqueline M.

AU - Yu, Kai

AU - Wheeler, William

AU - Zhang, Hong

AU - Cornelis, Marilyn C.

AU - Wright, Margaret E.

AU - Yeager, Meredith

AU - Snyder, Kirk

AU - Weinstein, Stephanie J.

AU - Mondul, Alison

AU - Eliassen, Heather

AU - Purdue, Mark

AU - Hazra, Aditi

AU - McCarty, Catherine A.

AU - Hendrickson, Sara

AU - Virtamo, Jarmo

AU - Hunter, David

AU - Chanock, Stephen

AU - Kraft, Peter

AU - Albanes, Demetrius

N1 - Funding Information: This work was supported in part by the Intramural Research Program of the National Institutes of Health and the National Cancer Institute. Additionally, the research was supported by Public Health Service contracts (N01-CN-45165, N01-RC-45035, N01-RC-37004 and HHSN261201000006C) from the National Cancer Institute, Department of Health and Human Services. S.H. is supported in part by training grant NIH 5 T32 CA09001-35. H.E. is supported in part by grant NIH R01 CA131218. Funding Information: Funding to pay the Open Access publication charges for this article was provided by the Intramural Program of the US National Cancer Institute, National Institutes of Health, Department of Health and Human Services.

PY - 2011/10

Y1 - 2011/10

N2 - 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.

AB - 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.

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

Abstract

Bibliographical note

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