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

Abstract

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/m2 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.

Evaluation of the Genetic Association Between Adult Obesity and Neuropsychiatric Disease

“…GPRIN2 is a regulator of neurite outgrowth(45) and expressed in the hypothalamus(27; 46). PPYR1 encodes a receptor for neuropeptide Y (NPY) and pancreatic polypeptide (PP) a potential regulator of food intake(32). This gene region has a number of segmental duplications with variable coverage across microarrays making definitive conclusions about this region difficult and CNVs across this region are not rare in the general population Our findings appear to be consistent with the SOS with greater overall prevalence of 10q11.2 duplications in EO vs O.…”

“…Smaller CNVs (both deletions and duplications) in this region have been associated with obesity(29)(30)(31). Increased copy number of PPYR1 (NPY4R), a gene within this region, have been associated with increased BMI, especially in women(32).…”

Low Salivary Amylase Gene (AMY1) Copy Number Is Associated with Obesity and Gut Prevotella Abundance in Mexican Children and Adults

“…The GPCR5 CNV deletion frequency was 0.025 in the Mexican population, and was not associated with obesity, which is consistent with the previous findings in Chinese individuals. Finally, previous studies associating the NPY4R CNV with obesity risk have reported contradictory findings, as the CNV deletion allele has been associated both with higher and lower obesity risk [ 14 , 15 , 41 , 42 ]. Our findings are consistent with the report of Sun et al, who found no association of this CNV deletion with obesity in the Chinese population [ 43 ].…”

Copy number determination of the gene for the human pancreatic polypeptide receptor NPY4R using read depth analysis and droplet digital PCR

“…This study was designed to investigate the previously reported CNV for the NPY4R gene on chromosome 10q11.22 and study the range of the CNV. Earlier studies were contradictory with the majority of studies reporting CNV [2, 5, 7–11, 14] and one study describing no variation in this genomic region [12]. Here, we demonstrate that the NPY4R copy number varied depending on the analysis method and the quality of data.…”

“…Most of the previous reports assumed that the normal copy number of NPY4R is 2 copies per genome [5, 9, 11–13] and describe the CNV as either gain or loss, not always specifying the exact copy number. Several studies have demonstrated that a CNV in this region is associated with differences in body weight [2, 5, 11, 13, 14].

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