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


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.
Zobel
Dorit P
DP
Steno Diabetes Center, Gentofte, Denmark. dpaj@steno.dk
Andreasen
Camilla H
CH
Grarup
Niels
N
Eiberg
Hans
H
Sørensen
Thorkild I A
TI
Sandbaek
Annelli
A
Lauritzen
Torsten
T
Borch-Johnsen
Knut
K
Jørgensen
Torben
T
Pedersen
Oluf
O
Hansen
Torben
T
D000328:Adult; D015992:Body Mass Index; D002096:C-Peptide / Q000097:blood; D016022:Case-Control Studies; D002784:Cholesterol / Q000097:blood; D003718:Denmark / Q000453:epidemiology; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007328:Insulin / Q000097:blood; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D040641:Quantitative Trait Loci; D044105:Receptor, Melanocortin, Type 4 / Q000235:genetics*; D018570:Risk Assessment; D014280:Triglycerides / Q000097:blood; D049629:Waist-Hip Ratio
D002096:C-Peptide; D007328:Insulin; C470072:MC4R protein, human; D044105:Receptor, Melanocortin, Type 4; D014280:Triglycerides; D002784:Cholesterol