Genome-wide association study of circulating retinol levels

Alison M. Mondul; Kai Yu; William Wheeler; Hong Zhang; Stephanie J. Weinstein; Jacqueline M. Major; Marilyn C. Cornelis; Satu Männistö; Aditi Hazra; Ann W. Hsing; Kevin B. Jacobs; Heather Eliassen; Toshiko Tanaka; Douglas J. Reding; Sara Hendrickson; Luigi Ferrucci; Jarmo Virtamo; David J. Hunter; Stephen J. Chanock; Peter Kraft; Demetrius Albanes

doi:10.1093/hmg/ddr387

Genome-wide association study of circulating retinol levels

Alison M. Mondul, Kai Yu, William Wheeler, Hong Zhang, Stephanie J. Weinstein, Jacqueline M. Major, Marilyn C. Cornelis, Satu Männistö, Aditi Hazra, Ann W. Hsing, Kevin B. Jacobs, Heather Eliassen, Toshiko Tanaka, Douglas J. Reding, Sara Hendrickson, Luigi Ferrucci, Jarmo Virtamo, David J. Hunter, Stephen J. Chanock, Peter KraftDemetrius Albanes

Research output: Contribution to journal › Article › peer-review

40 Scopus citations

Abstract

Retinol is one of the most biologically active forms of vitamin A and is hypothesized to influence a wide range of human diseases including asthma, cardiovascular disease, infectious diseases and cancer. We conducted a genome-wide association study of 5006 Caucasian individuals drawn from two cohorts of men: the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study and the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. We identified two independent single-nucleotide polymorphisms associated with circulating retinol levels, which are located near the transthyretin (TTR) and retinol binding protein 4 (RBP4) genes which encode major carrier proteins of retinol: rs1667255 (P =2.30× 10 ^-17) and rs10882272 (P =6.04× 10 ^-12). We replicated the association with rs10882272 in RBP4 in independent samples from the Nurses' Health Study and the Invecchiare in Chianti Study (InCHIANTI) that included 3792 women and 504 men (P =9.49× 10 ^-5), but found no association for retinol with rs1667255 in TTR among women, thus suggesting evidence for gender dimorphism (P-interaction=1.31× 10 ^-5). Discovery of common genetic variants associated with serum retinol levels may provide further insight into the contribution of retinol and other vitamin A compounds to the development of cancer and other complex diseases.

Original language	English (US)
Article number	ddr387
Pages (from-to)	4724-4731
Number of pages	8
Journal	Human molecular genetics
Volume	20
Issue number	23
DOIs	https://doi.org/10.1093/hmg/ddr387
State	Published - Dec 2011
Externally published	Yes

ASJC Scopus subject areas

Molecular Biology
Genetics
Genetics(clinical)

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10.1093/hmg/ddr387

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Mondul, A. M., Yu, K., Wheeler, W., Zhang, H., Weinstein, S. J., Major, J. M., Cornelis, M. C., Männistö, S., Hazra, A., Hsing, A. W., Jacobs, K. B., Eliassen, H., Tanaka, T., Reding, D. J., Hendrickson, S., Ferrucci, L., Virtamo, J., Hunter, D. J., Chanock, S. J., ... Albanes, D. (2011). Genome-wide association study of circulating retinol levels. Human molecular genetics, 20(23), 4724-4731. Article ddr387. https://doi.org/10.1093/hmg/ddr387

Mondul, AM, Yu, K, Wheeler, W, Zhang, H, Weinstein, SJ, Major, JM, Cornelis, MC, Männistö, S, Hazra, A, Hsing, AW, Jacobs, KB, Eliassen, H, Tanaka, T, Reding, DJ, Hendrickson, S, Ferrucci, L, Virtamo, J, Hunter, DJ, Chanock, SJ, Kraft, P & Albanes, D 2011, 'Genome-wide association study of circulating retinol levels', Human molecular genetics, vol. 20, no. 23, ddr387, pp. 4724-4731. https://doi.org/10.1093/hmg/ddr387

@article{593f56a6222a4e70ab10fa01606dc95f,

title = "Genome-wide association study of circulating retinol levels",

abstract = "Retinol is one of the most biologically active forms of vitamin A and is hypothesized to influence a wide range of human diseases including asthma, cardiovascular disease, infectious diseases and cancer. We conducted a genome-wide association study of 5006 Caucasian individuals drawn from two cohorts of men: the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study and the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. We identified two independent single-nucleotide polymorphisms associated with circulating retinol levels, which are located near the transthyretin (TTR) and retinol binding protein 4 (RBP4) genes which encode major carrier proteins of retinol: rs1667255 (P =2.30× 10 -17) and rs10882272 (P =6.04× 10 -12). We replicated the association with rs10882272 in RBP4 in independent samples from the Nurses' Health Study and the Invecchiare in Chianti Study (InCHIANTI) that included 3792 women and 504 men (P =9.49× 10 -5), but found no association for retinol with rs1667255 in TTR among women, thus suggesting evidence for gender dimorphism (P-interaction=1.31× 10 -5). Discovery of common genetic variants associated with serum retinol levels may provide further insight into the contribution of retinol and other vitamin A compounds to the development of cancer and other complex diseases.",

author = "Mondul, {Alison M.} and Kai Yu and William Wheeler and Hong Zhang and Weinstein, {Stephanie J.} and Major, {Jacqueline M.} and Cornelis, {Marilyn C.} and Satu M{\"a}nnist{\"o} and Aditi Hazra and Hsing, {Ann W.} and Jacobs, {Kevin B.} and Heather Eliassen and Toshiko Tanaka and Reding, {Douglas J.} and Sara Hendrickson and Luigi Ferrucci and Jarmo Virtamo and Hunter, {David J.} and Chanock, {Stephen J.} and Peter Kraft and Demetrius Albanes",

note = "Funding Information: The ATBC Study was supported by US 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, and by funding from the Intramural Research Program of the National Cancer Institute. S.H. is supported in part by training grant NIH 5 T32 CA09001-35. 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 = dec,

doi = "10.1093/hmg/ddr387",

language = "English (US)",

volume = "20",

pages = "4724--4731",

journal = "Human molecular genetics",

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T1 - Genome-wide association study of circulating retinol levels

AU - Mondul, Alison M.

AU - Yu, Kai

AU - Wheeler, William

AU - Zhang, Hong

AU - Weinstein, Stephanie J.

AU - Major, Jacqueline M.

AU - Cornelis, Marilyn C.

AU - Männistö, Satu

AU - Hazra, Aditi

AU - Hsing, Ann W.

AU - Jacobs, Kevin B.

AU - Eliassen, Heather

AU - Tanaka, Toshiko

AU - Reding, Douglas J.

AU - Hendrickson, Sara

AU - Ferrucci, Luigi

AU - Virtamo, Jarmo

AU - Hunter, David J.

AU - Chanock, Stephen J.

AU - Kraft, Peter

AU - Albanes, Demetrius

N1 - Funding Information: The ATBC Study was supported by US 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, and by funding from the Intramural Research Program of the National Cancer Institute. S.H. is supported in part by training grant NIH 5 T32 CA09001-35. 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 - 2011/12

Y1 - 2011/12

N2 - Retinol is one of the most biologically active forms of vitamin A and is hypothesized to influence a wide range of human diseases including asthma, cardiovascular disease, infectious diseases and cancer. We conducted a genome-wide association study of 5006 Caucasian individuals drawn from two cohorts of men: the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study and the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. We identified two independent single-nucleotide polymorphisms associated with circulating retinol levels, which are located near the transthyretin (TTR) and retinol binding protein 4 (RBP4) genes which encode major carrier proteins of retinol: rs1667255 (P =2.30× 10 -17) and rs10882272 (P =6.04× 10 -12). We replicated the association with rs10882272 in RBP4 in independent samples from the Nurses' Health Study and the Invecchiare in Chianti Study (InCHIANTI) that included 3792 women and 504 men (P =9.49× 10 -5), but found no association for retinol with rs1667255 in TTR among women, thus suggesting evidence for gender dimorphism (P-interaction=1.31× 10 -5). Discovery of common genetic variants associated with serum retinol levels may provide further insight into the contribution of retinol and other vitamin A compounds to the development of cancer and other complex diseases.

AB - Retinol is one of the most biologically active forms of vitamin A and is hypothesized to influence a wide range of human diseases including asthma, cardiovascular disease, infectious diseases and cancer. We conducted a genome-wide association study of 5006 Caucasian individuals drawn from two cohorts of men: the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study and the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. We identified two independent single-nucleotide polymorphisms associated with circulating retinol levels, which are located near the transthyretin (TTR) and retinol binding protein 4 (RBP4) genes which encode major carrier proteins of retinol: rs1667255 (P =2.30× 10 -17) and rs10882272 (P =6.04× 10 -12). We replicated the association with rs10882272 in RBP4 in independent samples from the Nurses' Health Study and the Invecchiare in Chianti Study (InCHIANTI) that included 3792 women and 504 men (P =9.49× 10 -5), but found no association for retinol with rs1667255 in TTR among women, thus suggesting evidence for gender dimorphism (P-interaction=1.31× 10 -5). Discovery of common genetic variants associated with serum retinol levels may provide further insight into the contribution of retinol and other vitamin A compounds to the development of cancer and other complex diseases.

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Genome-wide association study of circulating retinol levels

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