TY - JOUR
T1 - Variants near MC4R are associated with obesity and influence obesity-related quantitative traits in a population of middle-aged people
T2 - 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 - Sandbaek, Annelli
AU - Lauritzen, Torsten
AU - Borch-Johnsen, Knut
AU - Jørgensen, Torben
AU - Pedersen, Oluf
AU - Hansen, Torben
PY - 2009/3
Y1 - 2009/3
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, obesity in 14,940 individuals, and type 2 diabetes in 8,821 individuals.RESULTS: The minor risk alleles of rs17782313, rs17700633, and rs12970134 were associated with BMI (effect per allele 0.25 kg/m2, P = 0.01; 0.23, P = 0.01; and 0.31, P = 7 x 10(-4), respectively), waist circumference (0.67 cm, P = 0.006; 0.53, P = 0.02; and 0.85, P = 3 x 10(-4)), and body weight (1.04 kg, P = 6 x 10(-4); 0.71, P = 0.01; and 1.16, P = 8 x 10(-5)). In case-control studies of obesity defined by BMI, the minor C-allele of rs17782313 was associated with overweight/obesity and obesity (odds ratio [OR] 1.09, P = 0.006 and OR 1.12, P = 0.003, respectively). Similarly, the minor A-allele of rs17700633 was associated with overweight/obesity and obesity (1.12, P = 8 x 10(-5) and 1.16, P = 2 x 10(-5)), and the minor A-allele of rs12970134 was also associated with overweight/obesity and obesity (1.13, P = 2 x 10(-5) and 1.15, P = 6 x 10(-5)). rs477181, rs502933, and rs4450508 were not significantly associated with obesity in the Danish population. The frequency of the minor risk alleles of rs17782313 and rs12970134 was higher among patients with type 2 diabetes than among glucose-tolerant individuals (OR 1.08, P = 0.08 and 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, obesity in 14,940 individuals, and type 2 diabetes in 8,821 individuals.RESULTS: The minor risk alleles of rs17782313, rs17700633, and rs12970134 were associated with BMI (effect per allele 0.25 kg/m2, P = 0.01; 0.23, P = 0.01; and 0.31, P = 7 x 10(-4), respectively), waist circumference (0.67 cm, P = 0.006; 0.53, P = 0.02; and 0.85, P = 3 x 10(-4)), and body weight (1.04 kg, P = 6 x 10(-4); 0.71, P = 0.01; and 1.16, P = 8 x 10(-5)). In case-control studies of obesity defined by BMI, the minor C-allele of rs17782313 was associated with overweight/obesity and obesity (odds ratio [OR] 1.09, P = 0.006 and OR 1.12, P = 0.003, respectively). Similarly, the minor A-allele of rs17700633 was associated with overweight/obesity and obesity (1.12, P = 8 x 10(-5) and 1.16, P = 2 x 10(-5)), and the minor A-allele of rs12970134 was also associated with overweight/obesity and obesity (1.13, P = 2 x 10(-5) and 1.15, P = 6 x 10(-5)). rs477181, rs502933, and rs4450508 were not significantly associated with obesity in the Danish population. The frequency of the minor risk alleles of rs17782313 and rs12970134 was higher among patients with type 2 diabetes than among glucose-tolerant individuals (OR 1.08, P = 0.08 and 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.
KW - Adult
KW - Body Mass Index
KW - C-Peptide
KW - Case-Control Studies
KW - Cholesterol
KW - Denmark
KW - Genetic Variation
KW - Genotype
KW - Humans
KW - Insulin
KW - Middle Aged
KW - Obesity
KW - Quantitative Trait Loci
KW - Receptor, Melanocortin, Type 4
KW - Risk Assessment
KW - Triglycerides
KW - Waist-Hip Ratio
U2 - 10.2337/db08-0620
DO - 10.2337/db08-0620
M3 - Journal article
C2 - 19073769
SN - 0012-1797
VL - 58
SP - 757
EP - 764
JO - Diabetes
JF - Diabetes
IS - 3
ER -