Genome-wide association study suggested copy number variation may be associated with body mass index in the Chinese population

Obesity is a major public health problem characterized with high body mass index (BMI). Copy number variations (CNVs) have been identified to be associated with complex human diseases. The effect of CNVs on obesity is unknown. In this 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 (from 46.36 Mb to 46.56 Mb) was associated with BMI (the raw P=0.011). 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. Our findings suggested that CNV might be potentially important for the BMI variation. In addition, our study suggested that CNV might be used as a genetic marker to locate genes associated with BMI in Chinese population.

[1]  Philippe Froguel,et al.  Genome-wide association scans identified CTNNBL1 as a novel gene for obesity. , 2008, Human molecular genetics.

[2]  Yoshiji Yamada,et al.  Genetic factors for human obesity , 2008, Cellular and Molecular Life Sciences.

[3]  L. Armengol,et al.  X-chromosome tiling path array detection of copy number variants in patients with chromosome X-linked mental retardation , 2007, BMC Genomics.

[4]  Zachary A. Szpiech,et al.  Genotype, haplotype and copy-number variation in worldwide human populations , 2008, Nature.

[5]  D. Pinto,et al.  Structural variation of chromosomes in autism spectrum disorder. , 2008, American journal of human genetics.

[6]  M. During,et al.  Combined deletion of Y1, Y2, and Y4 receptors prevents hypothalamic neuropeptide Y overexpression-induced hyperinsulinemia despite persistence of hyperphagia and obesity. , 2006, Endocrinology.

[7]  Jing Huang,et al.  Dynamic model based algorithms for screening and genotyping over 100K SNPs on oligonucleotide microarrays , 2005, Bioinform..

[8]  G. Frost,et al.  Pancreatic polypeptide reduces appetite and food intake in humans. , 2003, The Journal of clinical endocrinology and metabolism.

[9]  A. Inui,et al.  Neuropeptide y receptor selective ligands in the treatment of obesity. , 2007, Endocrine reviews.

[10]  R. Rosmond.  Aetiology of obesity: a striving after wind? * , 2004, Obesity reviews : an official journal of the International Association for the Study of Obesity.

[11]  Bei-fan Zhou.  Predictive values of body mass index and waist circumference for risk factors of certain related diseases in Chinese adults--study on optimal cut-off points of body mass index and waist circumference in Chinese adults. , 2002, Biomedical and environmental sciences : BES.

[12]  K. Roeder,et al.  Genomic Control for Association Studies , 1999, Biometrics.

[13]  Herbert Herzog,et al.  Y4 receptor knockout rescues fertility in ob/ob mice. , 2002, Genes & development.

[14]  J. Holst,et al.  A role for pancreatic polypeptide in the regulation of gastric emptying and short-term metabolic control. , 2005, The Journal of clinical endocrinology and metabolism.

[15]  P. Donnelly,et al.  Inference of population structure using multilocus genotype data. , 2000, Genetics.

[16]  Edward R. Dougherty,et al.  SNiPer-HD: improved genotype calling accuracy by an expectation-maximization algorithm for high-density SNP arrays , 2007, Bioinform..

[17]  X. Estivill,et al.  Copy number variants and genetic traits: closer to the resolution of phenotypic to genotypic variability , 2007, Nature Reviews Genetics.

[18]  D. Conrad,et al.  Global variation in copy number in the human genome , 2006, Nature.

[19]  A. Stamford,et al.  Neuropeptide Y receptors as targets for anti-obesity drug development: perspective and current status. , 2002, European journal of pharmacology.

[20]  K. Clément,et al.  GAD2 on Chromosome 10p12 Is a Candidate Gene for Human Obesity , 2003, PLoS biology.

[21]  Bei-fan Zhou,et al.  Effect of body mass index on all-cause mortality and incidence of cardiovascular diseases--report for meta-analysis of prospective studies open optimal cut-off points of body mass index in Chinese adults. , 2002, Biomedical and environmental sciences : BES.

[22]  D. Conrad,et al.  A high-resolution survey of deletion polymorphism in the human genome , 2006, Nature Genetics.

[23]  Carolyn J. Brown,et al.  A comprehensive analysis of common copy-number variations in the human genome. , 2007, American journal of human genetics.

[24]  V. Colonna,et al.  Identification and Replication of a Novel Obesity Locus on Chromosome 1q24 in Isolated Populations of Cilento , 2008, Diabetes.

[25]  Terence P. Speed,et al.  Genome analysis A genotype calling algorithm for affymetrix SNP arrays , 2005 .

[26]  Lisa J. Martin,et al.  Quality assessment of buccal versus blood genomic DNA using the Affymetrix 500 K GeneChip , 2007, BMC Genetics.

[27]  D. Pinto,et al.  Copy-number variation in control population cohorts. , 2007, Human molecular genetics.

[28]  Philippe Froguel,et al.  Array CGH analysis of copy number variation identifies 1284 new genes variant in healthy white males: implications for association studies of complex diseases. , 2007, Human molecular genetics.

[29]  C. Mascie-Taylor,et al.  Human variation and body mass index: a review of the universality of BMI cut-offs, gender and urban-rural differences, and secular changes. , 2007, Journal of physiological anthropology.

[30]  N. Copeland,et al.  Assignment of the Y4 receptor gene (PPYR1) to human chromosome 10q11.2 and mouse chromosome 14. , 1997, Genomics.

[31]  D. Conrad,et al.  A worldwide survey of haplotype variation and linkage disequilibrium in the human genome , 2006, Nature Genetics.

[32]  P. Froguel,et al.  The genetics of human obesity , 2005, Nature Reviews Genetics.

[33]  Kenny Q. Ye,et al.  Large-Scale Copy Number Polymorphism in the Human Genome , 2004, Science.