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Multiple genetic studies have linked copy number variation (CNV) in different genes to body mass index (BMI) and obesity. A CNV on chromosome 10q11.22 has been associated with body weight. This CNV region spans  NPY4R , the gene encoding the pancreatic polypeptide receptor Y4, which has been described as a satiety-stimulating receptor. We have investigated CNV of the  NPY4R  gene and analysed its relationship to BMI, waist circumference and self-reported dietary intake from 558 individuals (216 men and 342 women) representing a wide BMI range. The copy number for  NPY4R  ranged from 2 to 8 copies (average 4.6±0.8). Rather than the expected negative correlation, we observed a positive correlation between  NPY4R  copy number and BMI as well as waist circumference (r = 0.267, p = 2.65×10 −7  and r = 0.256, p = 8×10 −7 , respectively). Each additional copy of  NPY4R  correlated with 2.6 kg/m 2  increase in BMI and 5.67 cm increase in waist circumference (p = 3.3×10 −7  and p = 1×10 −6 , respectively) for women. For men, there was no statistically significant correlation between CNV and BMI. Our results suggest that  NPY4R  genetic variation influences body weight in women, but the exact role of this receptor appears to be more complex than previously proposed.

Copy number of pancreatic polypeptide receptor gene NPY4R correlates with body mass index and waist circumference