Genetic variants in human CLOCK associate with total energy intake and cytokine sleep factors in overweight subjects (GOLDN population)

Marta Garaulet; Yu Chi Lee; Jian Shen; Laurence D. Parnell; Donna K. Arnett; Michael Y. Tsai; Chao Qiang Lai; Jose M. Ordovas

doi:10.1038/ejhg.2009.176

Genetic variants in human CLOCK associate with total energy intake and cytokine sleep factors in overweight subjects (GOLDN population)

Marta Garaulet, Yu Chi Lee, Jian Shen, Laurence D. Parnell, Donna K. Arnett, Michael Y. Tsai, Chao Qiang Lai, Jose M. Ordovas

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

85 Scopus citations

Abstract

Despite the importance of total energy intake in circadian system regulation, no study has related human CLOCK gene polymorphisms and food-intake measures. The aim of this study was to analyze the associations of CLOCK single-nucleotide polymorphisms (SNPs) with food intake and to explore the specific role of the cytokine system. A total of 1100 individual participants in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study were included. Dietary intake was estimated with a validated questionnaire. Interleukin-6 (IL-6), monocyte chemotactic protein 1 (MCP1), tumor necrosis factor-α (TNF-α), IL-2 soluble receptor-α (IL-2sR-α) and adiponectin plasma concentrations were measured. Our results showed that four of five CLOCK SNPs selected were significantly associated with total energy intake (P0.05). For SNP rs3749474, the energy intake and total fat, protein and carbohydrate intakes were significantly higher in minor allele carriers than in non-carriers. Frequency of the minor allele was greater in subjects with high energy intake than in those with low intake. Subjects with the minor allele were 1.33 times more likely to have high energy intake than non-carriers (95% CI 1.09-1.72, P0.0350). All CLOCK SNPs were associated with plasma cytokine values, in particular with those that were highly correlated with energy intake: MCP1, IL-6 and adiponectin. Interestingly, minor allele carriers with high energy intake showed decreased cytokine values, which could be related with a lower anorectic effect and decreased sleep in these subjects. In conclusion, we show a novel association of genetic variation at CLOCK with total energy intake, which was particularly relevant for SNP rs3749474. Associations could be mediated through the alteration of cytokine levels that may influence energy intake and sleep pattern.

Original language	English
Pages (from-to)	364-369
Number of pages	6
Journal	European Journal of Human Genetics
Volume	18
Issue number	3
DOIs	https://doi.org/10.1038/ejhg.2009.176
State	Published - Mar 2010

Bibliographical note

Funding Information:
The study sample consisted of 540 men and 560 women who participated in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study. GOLDN is part of the Program for Genetic Interactions Network and is funded by the NIH through the University of Alabama at Birmingham and in collaboration with the University of Utah, Washington University, Tufts University, University of Texas, University of Michigan, University of Minnesota and Fairview University of Minnesota Medical Center. The majority of participants were re-recruited from three-generational pedigrees from two National Heart, Lung, and Blood Institute Family Heart Study field centers (Minneapolis, Minnesota, and Salt Lake City, Utah).17 Nearly all individuals were of European descent. The details of the study are available at https:// dsgweb.wustl.edu/goldn/. The protocol was approved by the institutional review boards of the University of Alabama, the University of Minnesota, the University of Utah and the Tufts University. To avoid using data from under-reporters of total energy intake, all subjects who reported less than 600 kcal/day of energy intake were excluded from the study, resulting in a final sample size of 1100 individuals.

Funding Information:
This work was supported by the Seneca Foundation from the Government of Murcia (project 02934/PI/05 to MG), the Government of Education, Science and Research of Murcia (Project BIO/FFA 07/01-0004) and by The Spanish Government of Science and Innovation (projects AGL2008-01655/ALI) and by Grants U01 HL72524 and HL-54776 from the National Institutes of Health, and DK075030 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), and contracts 53-K06-5-10 and 58-1950-9-001 from the US Department of Agriculture Research Service. JMO.

Funding

The study sample consisted of 540 men and 560 women who participated in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study. GOLDN is part of the Program for Genetic Interactions Network and is funded by the NIH through the University of Alabama at Birmingham and in collaboration with the University of Utah, Washington University, Tufts University, University of Texas, University of Michigan, University of Minnesota and Fairview University of Minnesota Medical Center. The majority of participants were re-recruited from three-generational pedigrees from two National Heart, Lung, and Blood Institute Family Heart Study field centers (Minneapolis, Minnesota, and Salt Lake City, Utah).17 Nearly all individuals were of European descent. The details of the study are available at https:// dsgweb.wustl.edu/goldn/. The protocol was approved by the institutional review boards of the University of Alabama, the University of Minnesota, the University of Utah and the Tufts University. To avoid using data from under-reporters of total energy intake, all subjects who reported less than 600 kcal/day of energy intake were excluded from the study, resulting in a final sample size of 1100 individuals. This work was supported by the Seneca Foundation from the Government of Murcia (project 02934/PI/05 to MG), the Government of Education, Science and Research of Murcia (Project BIO/FFA 07/01-0004) and by The Spanish Government of Science and Innovation (projects AGL2008-01655/ALI) and by Grants U01 HL72524 and HL-54776 from the National Institutes of Health, and DK075030 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), and contracts 53-K06-5-10 and 58-1950-9-001 from the US Department of Agriculture Research Service. JMO.

Funders	Funder number
Fairview University of Minnesota Medical Center
Government of Education, Science and Research of Murcia	BIO/FFA 07/01-0004
Government of Murcia	02934/PI/05
US Department of Agriculture Research Service
University of Texas, University of Michigan
The George Washington University
National Institutes of Health (NIH)	DK075030
National Heart, Lung, and Blood Institute (NHLBI)	U01HL072524
National Institute of Diabetes and Digestive and Kidney Diseases	58-1950-9-001, 53-K06-5-10
Minnesota State University-Mankato
University of Utah Health
Fundación Séneca
Tufts University
University of Alabama, Birmingham
Ministerio de Ciencia e Innovación, Spain	HL-54776, U01 HL72524, AGL2008-01655/ALI

Keywords

CLOCK
Circadian
Energy intake
Interleukin-6
Metabolic syndrome
Obesity

ASJC Scopus subject areas

Genetics
Genetics(clinical)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/ejhg.2009.176

Cite this

@article{917b2e6a0104444b8e5f505e42b5cdd6,

title = "Genetic variants in human CLOCK associate with total energy intake and cytokine sleep factors in overweight subjects (GOLDN population)",

abstract = "Despite the importance of total energy intake in circadian system regulation, no study has related human CLOCK gene polymorphisms and food-intake measures. The aim of this study was to analyze the associations of CLOCK single-nucleotide polymorphisms (SNPs) with food intake and to explore the specific role of the cytokine system. A total of 1100 individual participants in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study were included. Dietary intake was estimated with a validated questionnaire. Interleukin-6 (IL-6), monocyte chemotactic protein 1 (MCP1), tumor necrosis factor-α (TNF-α), IL-2 soluble receptor-α (IL-2sR-α) and adiponectin plasma concentrations were measured. Our results showed that four of five CLOCK SNPs selected were significantly associated with total energy intake (P0.05). For SNP rs3749474, the energy intake and total fat, protein and carbohydrate intakes were significantly higher in minor allele carriers than in non-carriers. Frequency of the minor allele was greater in subjects with high energy intake than in those with low intake. Subjects with the minor allele were 1.33 times more likely to have high energy intake than non-carriers (95% CI 1.09-1.72, P0.0350). All CLOCK SNPs were associated with plasma cytokine values, in particular with those that were highly correlated with energy intake: MCP1, IL-6 and adiponectin. Interestingly, minor allele carriers with high energy intake showed decreased cytokine values, which could be related with a lower anorectic effect and decreased sleep in these subjects. In conclusion, we show a novel association of genetic variation at CLOCK with total energy intake, which was particularly relevant for SNP rs3749474. Associations could be mediated through the alteration of cytokine levels that may influence energy intake and sleep pattern.",

keywords = "CLOCK, Circadian, Energy intake, Interleukin-6, Metabolic syndrome, Obesity",

author = "Marta Garaulet and Lee, {Yu Chi} and Jian Shen and Parnell, {Laurence D.} and Arnett, {Donna K.} and Tsai, {Michael Y.} and Lai, {Chao Qiang} and Ordovas, {Jose M.}",

note = "Funding Information: The study sample consisted of 540 men and 560 women who participated in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study. GOLDN is part of the Program for Genetic Interactions Network and is funded by the NIH through the University of Alabama at Birmingham and in collaboration with the University of Utah, Washington University, Tufts University, University of Texas, University of Michigan, University of Minnesota and Fairview University of Minnesota Medical Center. The majority of participants were re-recruited from three-generational pedigrees from two National Heart, Lung, and Blood Institute Family Heart Study field centers (Minneapolis, Minnesota, and Salt Lake City, Utah).17 Nearly all individuals were of European descent. The details of the study are available at https:// dsgweb.wustl.edu/goldn/. The protocol was approved by the institutional review boards of the University of Alabama, the University of Minnesota, the University of Utah and the Tufts University. To avoid using data from under-reporters of total energy intake, all subjects who reported less than 600 kcal/day of energy intake were excluded from the study, resulting in a final sample size of 1100 individuals. Funding Information: This work was supported by the Seneca Foundation from the Government of Murcia (project 02934/PI/05 to MG), the Government of Education, Science and Research of Murcia (Project BIO/FFA 07/01-0004) and by The Spanish Government of Science and Innovation (projects AGL2008-01655/ALI) and by Grants U01 HL72524 and HL-54776 from the National Institutes of Health, and DK075030 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), and contracts 53-K06-5-10 and 58-1950-9-001 from the US Department of Agriculture Research Service. JMO.",

year = "2010",

month = mar,

doi = "10.1038/ejhg.2009.176",

language = "English",

volume = "18",

pages = "364--369",

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TY - JOUR

T1 - Genetic variants in human CLOCK associate with total energy intake and cytokine sleep factors in overweight subjects (GOLDN population)

AU - Garaulet, Marta

AU - Lee, Yu Chi

AU - Shen, Jian

AU - Parnell, Laurence D.

AU - Arnett, Donna K.

AU - Tsai, Michael Y.

AU - Lai, Chao Qiang

AU - Ordovas, Jose M.

N1 - Funding Information: The study sample consisted of 540 men and 560 women who participated in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study. GOLDN is part of the Program for Genetic Interactions Network and is funded by the NIH through the University of Alabama at Birmingham and in collaboration with the University of Utah, Washington University, Tufts University, University of Texas, University of Michigan, University of Minnesota and Fairview University of Minnesota Medical Center. The majority of participants were re-recruited from three-generational pedigrees from two National Heart, Lung, and Blood Institute Family Heart Study field centers (Minneapolis, Minnesota, and Salt Lake City, Utah).17 Nearly all individuals were of European descent. The details of the study are available at https:// dsgweb.wustl.edu/goldn/. The protocol was approved by the institutional review boards of the University of Alabama, the University of Minnesota, the University of Utah and the Tufts University. To avoid using data from under-reporters of total energy intake, all subjects who reported less than 600 kcal/day of energy intake were excluded from the study, resulting in a final sample size of 1100 individuals. Funding Information: This work was supported by the Seneca Foundation from the Government of Murcia (project 02934/PI/05 to MG), the Government of Education, Science and Research of Murcia (Project BIO/FFA 07/01-0004) and by The Spanish Government of Science and Innovation (projects AGL2008-01655/ALI) and by Grants U01 HL72524 and HL-54776 from the National Institutes of Health, and DK075030 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), and contracts 53-K06-5-10 and 58-1950-9-001 from the US Department of Agriculture Research Service. JMO.

PY - 2010/3

Y1 - 2010/3

N2 - Despite the importance of total energy intake in circadian system regulation, no study has related human CLOCK gene polymorphisms and food-intake measures. The aim of this study was to analyze the associations of CLOCK single-nucleotide polymorphisms (SNPs) with food intake and to explore the specific role of the cytokine system. A total of 1100 individual participants in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study were included. Dietary intake was estimated with a validated questionnaire. Interleukin-6 (IL-6), monocyte chemotactic protein 1 (MCP1), tumor necrosis factor-α (TNF-α), IL-2 soluble receptor-α (IL-2sR-α) and adiponectin plasma concentrations were measured. Our results showed that four of five CLOCK SNPs selected were significantly associated with total energy intake (P0.05). For SNP rs3749474, the energy intake and total fat, protein and carbohydrate intakes were significantly higher in minor allele carriers than in non-carriers. Frequency of the minor allele was greater in subjects with high energy intake than in those with low intake. Subjects with the minor allele were 1.33 times more likely to have high energy intake than non-carriers (95% CI 1.09-1.72, P0.0350). All CLOCK SNPs were associated with plasma cytokine values, in particular with those that were highly correlated with energy intake: MCP1, IL-6 and adiponectin. Interestingly, minor allele carriers with high energy intake showed decreased cytokine values, which could be related with a lower anorectic effect and decreased sleep in these subjects. In conclusion, we show a novel association of genetic variation at CLOCK with total energy intake, which was particularly relevant for SNP rs3749474. Associations could be mediated through the alteration of cytokine levels that may influence energy intake and sleep pattern.

AB - Despite the importance of total energy intake in circadian system regulation, no study has related human CLOCK gene polymorphisms and food-intake measures. The aim of this study was to analyze the associations of CLOCK single-nucleotide polymorphisms (SNPs) with food intake and to explore the specific role of the cytokine system. A total of 1100 individual participants in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study were included. Dietary intake was estimated with a validated questionnaire. Interleukin-6 (IL-6), monocyte chemotactic protein 1 (MCP1), tumor necrosis factor-α (TNF-α), IL-2 soluble receptor-α (IL-2sR-α) and adiponectin plasma concentrations were measured. Our results showed that four of five CLOCK SNPs selected were significantly associated with total energy intake (P0.05). For SNP rs3749474, the energy intake and total fat, protein and carbohydrate intakes were significantly higher in minor allele carriers than in non-carriers. Frequency of the minor allele was greater in subjects with high energy intake than in those with low intake. Subjects with the minor allele were 1.33 times more likely to have high energy intake than non-carriers (95% CI 1.09-1.72, P0.0350). All CLOCK SNPs were associated with plasma cytokine values, in particular with those that were highly correlated with energy intake: MCP1, IL-6 and adiponectin. Interestingly, minor allele carriers with high energy intake showed decreased cytokine values, which could be related with a lower anorectic effect and decreased sleep in these subjects. In conclusion, we show a novel association of genetic variation at CLOCK with total energy intake, which was particularly relevant for SNP rs3749474. Associations could be mediated through the alteration of cytokine levels that may influence energy intake and sleep pattern.

KW - CLOCK

KW - Circadian

KW - Energy intake

KW - Interleukin-6

KW - Metabolic syndrome

KW - Obesity

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Genetic variants in human CLOCK associate with total energy intake and cytokine sleep factors in overweight subjects (GOLDN population)

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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