Genome-wide Copy Number Variation Study Associated With Obesity In Chinese Population

Obesity is a serious public health problem,and it has been defined by World Health Organization(WHO) based on body mass index(BMI).BMI is a convenient,simple and popularly adopted method to evaluate obesity.Over the years,obesity-related mortality had consistently increased。Several genomic regions and candidate genes have been identified to contribute genetic variants for obesity by previous linkage studies,candidate gene studies and recent genome-wide association studies. However,none of these genes or genomic regions has been found to explain more than 10%of variation in any obesity phenotypes. This leaves largely unknown genetic factors underlying obesity。Copy number variation(CNV) has been identified to be associated with human complex diseases.The effect of CNVs on obesity is unknown.In the present study,we explored the association of CNVs with BMI in 597 Chinese Han subjects using Affymetrix GeneChip^? Human Mapping 500K Array Set.We found that one CNV at 10q11.22(named CNV 10q11.22,from 46.36Mb to 46.56Mb) was associated with BMI(P=0.011).Association analyses showed CNV 10q11.22 loss was significantly associated with higher BMI.Compared to the 567 subjects with two gene copy numbers(normal diploid),subjects with CNV 10q11.22 loss(copy number＜2) had 12.4%higher BMI value,and subjects with CNV 10q11.22 gain(copy number＞2) had 5.4%lower BMI value.The CNV contributed 1.6%of BMI variation, and it covered one important obesity gene - pancreatic polypeptide receptor 1(PPYR1).It was reported that PPYR1 was a key regulator of energy homeostasis and be hoped as a potential target to treat human obesity.Our findings suggested that CNV may be potentially important for BMI variation,the variation of gene dosage may play potentially significant role for obesity.In addition,our study suggested that CNV may be used as a genetic marker to locate genes associated with obesity in Chinese population.