Variants near MC4R associate with obesity and influence obesity-related quantitative traits in a population of middle-aged people: studies of 14,940 Danes

Dorit P Zobel; Camilla H Andreasen; Niels Grarup; Hans Eiberg; Thorkild I A Sørensen; Annelli Sandbæk; Torsten Lauritzen; Knut Borch-Johnsen; Torben Jørgensen; Oluf Pedersen; Torben Hansen

doi:10.2337/db08-0620

Variants near MC4R associate with obesity and influence obesity-related quantitative traits in a population of middle-aged people: studies of 14,940 Danes

Dorit P Zobel, Camilla H Andreasen, Niels Grarup, Hans Eiberg, Thorkild I A Sørensen, Annelli Sandbæk, Torsten Lauritzen, Knut Borch-Johnsen, Torben Jørgensen, Oluf Pedersen, Torben Hansen

71 Citations (Scopus)

Abstract

Objective: Variants downstream of the melanocortin-4 receptor gene (MC4R) have been reported to associate with obesity. We examined rs17782313, rs17700633, rs12970134, rs477181, rs502933, and rs4450508 near MC4R for association with obesity-related quantitative traits, obesity, and type 2 diabetes in Danish individuals. Research Design and Methods: The variants were investigated for association with obesity-related quantitative traits in 5,807 population-based-sampled individuals, for association with obesity in 14,940 individuals, and for association with type 2 diabetes in 8,821 individuals. Results: The minor risk alleles of rs17782313, rs17700633, and rs12970134 associated with BMI (effect per-allele: 0.25 [P=0.01], 0.23 [P=0.01], and 0.31 [P=7x10(-4)] kg/m(2), respectively); waist circumference (effect per-allele: 0.67 [P=0.006], 0.53 [P=0.02], and 0.85 [P=3x10(-4)] cm, respectively); and body weight (effect per-allele: 1.04 [P=6x10(-4)], 0.71 [P=0.01], and 1.16 [P=8x10(-5)] kg, respectively). In case-control studies of obesity defined by BMI the minor C-allele of rs17782313 associated with overweight/obesity and obesity (OR(overweight/obesity)=1.09, P=0.006; OR(obesity)=1.12, P=0.003). Similarly, the minor A-allele of rs17700633 associated with overweight/obesity and obesity (OR(overweight/obesity)=1.12, P=8x10(-5); OR(obesity)=1.16, P=2x10(-5)), and the minor A-allele of rs12970134 was also associated with overweight/obesity and obesity (OR(overweight/obesity)=1.13, P=2x10(-5); OR(obesity)=1.15, P=6x10(-5)). rs477181, rs502933, and rs4450508 were not statistically significantly associated with obesity in the Danish population. The frequency of the minor risk alleles of rs17782313 and rs12970134 were higher among patients with type 2 diabetes compared with glucose-tolerant individuals (OR=1.08, P=0.08; and OR=1.08, P=0.06, respectively); however, these borderline associations were abolished after adjustment for BMI. Conclusions: rs17782313, rs17700633, and rs12970134 near MC4R associate with measures of obesity in Danish individuals.

Original language	English
Journal	Diabetes
Pages (from-to)	757-764
Number of pages	8
ISSN	0012-1797
DOIs	https://doi.org/10.2337/db08-0620
Publication status	Published - 2009

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10.2337/db08-0620

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Zobel, D. P., Andreasen, C. H., Grarup, N., Eiberg, H., Sørensen, T. I. A., Sandbæk, A., Lauritzen, T., Borch-Johnsen, K., Jørgensen, T., Pedersen, O., & Hansen, T. (2009). Variants near MC4R associate with obesity and influence obesity-related quantitative traits in a population of middle-aged people: studies of 14,940 Danes. Diabetes, 757-764. https://doi.org/10.2337/db08-0620

@article{98e93190ee1b11ddbf70000ea68e967b,

title = "Variants near MC4R associate with obesity and influence obesity-related quantitative traits in a population of middle-aged people: studies of 14,940 Danes",

abstract = "Objective: Variants downstream of the melanocortin-4 receptor gene (MC4R) have been reported to associate with obesity. We examined rs17782313, rs17700633, rs12970134, rs477181, rs502933, and rs4450508 near MC4R for association with obesity-related quantitative traits, obesity, and type 2 diabetes in Danish individuals. Research Design and Methods: The variants were investigated for association with obesity-related quantitative traits in 5,807 population-based-sampled individuals, for association with obesity in 14,940 individuals, and for association with type 2 diabetes in 8,821 individuals. Results: The minor risk alleles of rs17782313, rs17700633, and rs12970134 associated with BMI (effect per-allele: 0.25 [P=0.01], 0.23 [P=0.01], and 0.31 [P=7x10(-4)] kg/m(2), respectively); waist circumference (effect per-allele: 0.67 [P=0.006], 0.53 [P=0.02], and 0.85 [P=3x10(-4)] cm, respectively); and body weight (effect per-allele: 1.04 [P=6x10(-4)], 0.71 [P=0.01], and 1.16 [P=8x10(-5)] kg, respectively). In case-control studies of obesity defined by BMI the minor C-allele of rs17782313 associated with overweight/obesity and obesity (OR(overweight/obesity)=1.09, P=0.006; OR(obesity)=1.12, P=0.003). Similarly, the minor A-allele of rs17700633 associated with overweight/obesity and obesity (OR(overweight/obesity)=1.12, P=8x10(-5); OR(obesity)=1.16, P=2x10(-5)), and the minor A-allele of rs12970134 was also associated with overweight/obesity and obesity (OR(overweight/obesity)=1.13, P=2x10(-5); OR(obesity)=1.15, P=6x10(-5)). rs477181, rs502933, and rs4450508 were not statistically significantly associated with obesity in the Danish population. The frequency of the minor risk alleles of rs17782313 and rs12970134 were higher among patients with type 2 diabetes compared with glucose-tolerant individuals (OR=1.08, P=0.08; and OR=1.08, P=0.06, respectively); however, these borderline associations were abolished after adjustment for BMI. Conclusions: rs17782313, rs17700633, and rs12970134 near MC4R associate with measures of obesity in Danish individuals.",

author = "Zobel, {Dorit P} and Andreasen, {Camilla H} and Niels Grarup and Hans Eiberg and S{\o}rensen, {Thorkild I A} and Annelli Sandb{\ae}k and Torsten Lauritzen and Knut Borch-Johnsen and Torben J{\o}rgensen and Oluf Pedersen and Torben Hansen",

year = "2009",

doi = "10.2337/db08-0620",

language = "English",

pages = "757--764",

journal = "Diabetes",

issn = "0012-1797",

publisher = "American Diabetes Association",

}

TY - JOUR

T1 - Variants near MC4R associate with obesity and influence obesity-related quantitative traits in a population of middle-aged people: studies of 14,940 Danes

AU - Zobel, Dorit P

AU - Andreasen, Camilla H

AU - Grarup, Niels

AU - Eiberg, Hans

AU - Sørensen, Thorkild I A

AU - Sandbæk, Annelli

AU - Lauritzen, Torsten

AU - Borch-Johnsen, Knut

AU - Jørgensen, Torben

AU - Pedersen, Oluf

AU - Hansen, Torben

PY - 2009

Y1 - 2009

N2 - Objective: Variants downstream of the melanocortin-4 receptor gene (MC4R) have been reported to associate with obesity. We examined rs17782313, rs17700633, rs12970134, rs477181, rs502933, and rs4450508 near MC4R for association with obesity-related quantitative traits, obesity, and type 2 diabetes in Danish individuals. Research Design and Methods: The variants were investigated for association with obesity-related quantitative traits in 5,807 population-based-sampled individuals, for association with obesity in 14,940 individuals, and for association with type 2 diabetes in 8,821 individuals. Results: The minor risk alleles of rs17782313, rs17700633, and rs12970134 associated with BMI (effect per-allele: 0.25 [P=0.01], 0.23 [P=0.01], and 0.31 [P=7x10(-4)] kg/m(2), respectively); waist circumference (effect per-allele: 0.67 [P=0.006], 0.53 [P=0.02], and 0.85 [P=3x10(-4)] cm, respectively); and body weight (effect per-allele: 1.04 [P=6x10(-4)], 0.71 [P=0.01], and 1.16 [P=8x10(-5)] kg, respectively). In case-control studies of obesity defined by BMI the minor C-allele of rs17782313 associated with overweight/obesity and obesity (OR(overweight/obesity)=1.09, P=0.006; OR(obesity)=1.12, P=0.003). Similarly, the minor A-allele of rs17700633 associated with overweight/obesity and obesity (OR(overweight/obesity)=1.12, P=8x10(-5); OR(obesity)=1.16, P=2x10(-5)), and the minor A-allele of rs12970134 was also associated with overweight/obesity and obesity (OR(overweight/obesity)=1.13, P=2x10(-5); OR(obesity)=1.15, P=6x10(-5)). rs477181, rs502933, and rs4450508 were not statistically significantly associated with obesity in the Danish population. The frequency of the minor risk alleles of rs17782313 and rs12970134 were higher among patients with type 2 diabetes compared with glucose-tolerant individuals (OR=1.08, P=0.08; and OR=1.08, P=0.06, respectively); however, these borderline associations were abolished after adjustment for BMI. Conclusions: rs17782313, rs17700633, and rs12970134 near MC4R associate with measures of obesity in Danish individuals.

AB - Objective: Variants downstream of the melanocortin-4 receptor gene (MC4R) have been reported to associate with obesity. We examined rs17782313, rs17700633, rs12970134, rs477181, rs502933, and rs4450508 near MC4R for association with obesity-related quantitative traits, obesity, and type 2 diabetes in Danish individuals. Research Design and Methods: The variants were investigated for association with obesity-related quantitative traits in 5,807 population-based-sampled individuals, for association with obesity in 14,940 individuals, and for association with type 2 diabetes in 8,821 individuals. Results: The minor risk alleles of rs17782313, rs17700633, and rs12970134 associated with BMI (effect per-allele: 0.25 [P=0.01], 0.23 [P=0.01], and 0.31 [P=7x10(-4)] kg/m(2), respectively); waist circumference (effect per-allele: 0.67 [P=0.006], 0.53 [P=0.02], and 0.85 [P=3x10(-4)] cm, respectively); and body weight (effect per-allele: 1.04 [P=6x10(-4)], 0.71 [P=0.01], and 1.16 [P=8x10(-5)] kg, respectively). In case-control studies of obesity defined by BMI the minor C-allele of rs17782313 associated with overweight/obesity and obesity (OR(overweight/obesity)=1.09, P=0.006; OR(obesity)=1.12, P=0.003). Similarly, the minor A-allele of rs17700633 associated with overweight/obesity and obesity (OR(overweight/obesity)=1.12, P=8x10(-5); OR(obesity)=1.16, P=2x10(-5)), and the minor A-allele of rs12970134 was also associated with overweight/obesity and obesity (OR(overweight/obesity)=1.13, P=2x10(-5); OR(obesity)=1.15, P=6x10(-5)). rs477181, rs502933, and rs4450508 were not statistically significantly associated with obesity in the Danish population. The frequency of the minor risk alleles of rs17782313 and rs12970134 were higher among patients with type 2 diabetes compared with glucose-tolerant individuals (OR=1.08, P=0.08; and OR=1.08, P=0.06, respectively); however, these borderline associations were abolished after adjustment for BMI. Conclusions: rs17782313, rs17700633, and rs12970134 near MC4R associate with measures of obesity in Danish individuals.

U2 - 10.2337/db08-0620

DO - 10.2337/db08-0620

M3 - Journal article

C2 - 19073769

SN - 0012-1797

SP - 757

EP - 764

JO - Diabetes

JF - Diabetes

ER -

Variants near MC4R associate with obesity and influence obesity-related quantitative traits in a population of middle-aged people: studies of 14,940 Danes

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