title: Copy number variation on chromosome 10q26.3 for obesity identified by a genome-wide study.
abstract: BACKGROUND
  Obesity is a highly heritable disease defined by high body mass index (BMI). However, a large proportion of the heritability of obesity remains unexplained. Copy number variations (CNVs) might contribute to the missing heritability of obesity.
  
  
  METHODS
  We conducted genome-wide CNV analyses on obesity phenotypes, including BMI and body fat mass in a discovery sample of 2215 unrelated white subjects. After quality control, 314 CNVs were used for association tests. For significant CNVs identified, follow-up replication analyses were performed in three independent samples, including an unrelated sample of 1000 white subjects (OM sample), a family-based sample of 8385 white subjects (FHS sample), and an African-American sample of 1479 obesity cases and 1575 lean controls (AA sample).
  
  
  RESULTS
  Genome-wide CNV analyses detected that a CNV located at 10q26.3, which, even after multiple testing corrections, showed a strong association with both BMI (P = 2.30 × 10(-4), β = 2.164) and body fat mass (P = 6.76 × 10(-5), β = 4.126). This CNV was successfully replicated in the three replication samples (OM sample: P = 0.0465 for BMI, 0.0435 for fat mass; FHS sample: P = 0.0038 for BMI; AA sample: P = 0.0023 for obesity). Quantitative PCR validated this CNV, which covers a gene, CYP2E1. The protein encoded by CYP2E1 involves the synthesis of cholesterol, steroids and other lipids, which may have a potential impact on obesity.
  
  
  CONCLUSIONS
  Our findings suggest the significant contribution of CNV10q26.3 to the pathogenesis of obesity.
authors.affiliation: 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 710049, People's Republic of China.
authors.forename: Tie-Lin
authors.initials: TL
authors.lastname: Yang
authors.forename: Yan
authors.initials: Y
authors.lastname: Guo
authors.forename: Hui
authors.initials: H
authors.lastname: Shen
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.forename: Joseph T
authors.initials: JT
authors.lastname: Glessner
authors.forename: Chuan
authors.initials: C
authors.lastname: Qiu
authors.forename: Fei-Yan
authors.initials: FY
authors.lastname: Deng
authors.forename: Qing
authors.initials: Q
authors.lastname: Tian
authors.forename: Ping
authors.initials: P
authors.lastname: Yu
authors.forename: Yao-Zhong
authors.initials: YZ
authors.lastname: Liu
authors.forename: Yong-Jun
authors.initials: YJ
authors.lastname: Liu
authors.forename: Hakon
authors.initials: H
authors.lastname: Hakonarson
authors.forename: Struan F A
authors.initials: SF
authors.lastname: Grant
authors.forename: Hong-Wen
authors.initials: HW
authors.lastname: Deng
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics; D015992:Body Mass Index; D016022:Case-Control Studies; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics; D056915:DNA Copy Number Variations / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D009765:Obesity / Q000208:ethnology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D054928:Validation Studies as Topic; D044465:White People / Q000235:genetics