title: Copy number variations at the Prader-Willi syndrome region on chromosome 15 and associations with obesity in whites.
abstract: Obesity is a serious health problem with strong genetic determination. Copy number variation (CNV) is a common type of genomic variant associated with some complex human diseases. However, it is not clear how CNVs contribute to the etiology of obesity. In this study, we examined 1,000 unrelated US whites to search for CNVs that may predispose to obesity. We focused our analyses on the Prader-Willi syndrome (PWS) critical region (chromosome 15q11-q13), because the PWS region is a hotspot for CNV generation and obesity is one of the major clinical manifestations for chromosome abnormalities at this region. We constructed a map containing 39 CNVs at the PWS critical region with CNV occurrence rates higher than 1%. Among them, three CNVs were significantly associated with body fat mass (P < 0.05), with a higher copy number (CN) associated with an increase of 5.08-9.77 kg in body fat mass. These three CNVs are close to two known PWS genes, NDN (necdin homolog) and C15orf2 (chromosome 15 open reading frame 2), and partially overlap with another obesity gene PWRN1 (Prader-Willi region nonprotein-coding RNA 1). Interestingly, our recently published whole genome association scan study using the same sample by examining single-nucleotide polymorphisms (SNPs) did not find any significant associations at these CNV regions, suggesting the importance of examining both CNVs and SNPs for better understanding of genetic basis of obesity. Further studies are warranted to validate these CNVs and their importance to obesity.
authors.affiliation: The Key Laboratory of Biomedical Information Engineering of Ministry of Education and Institute of Molecular Genetics, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi, The People's Republic of China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Chen
authors.forename: Yong-Jun
authors.initials: YJ
authors.lastname: Liu
authors.forename: Yu-Fang
authors.initials: YF
authors.lastname: Pei
authors.forename: Tie-Lin
authors.initials: TL
authors.lastname: Yang
authors.forename: Fei-Yan
authors.initials: FY
authors.lastname: Deng
authors.forename: Xiao-Gang
authors.initials: XG
authors.lastname: Liu
authors.forename: Ding-You
authors.initials: DY
authors.lastname: Li
authors.forename: Hong-Wen
authors.initials: HW
authors.lastname: Deng
mesh_terms: D050154:Adiposity; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015992:Body Mass Index; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D056915:DNA Copy Number Variations; D005260:Female; D018628:Gene Dosage; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D015146:Midwestern United States; D009765:Obesity / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D016366:Open Reading Frames; D020161:Physical Chromosome Mapping; D020641:Polymorphism, Single Nucleotide; D011218:Prader-Willi Syndrome / Q000235:genetics*; D044465:White People; D055815:Young Adult