title: Current limitations of SNP data from the public domain for studies of complex disorders: a test for ten candidate genes for obesity and osteoporosis.
abstract: BACKGROUND
  Public SNP databases are frequently used to choose SNPs for candidate genes in the association and linkage studies of complex disorders. However, their utility for such studies of diseases with ethnic-dependent background has never been evaluated.
  
  
  RESULTS
  To estimate the accuracy and completeness of SNP public databases, we analyzed the allele frequencies of 41 SNPs in 10 candidate genes for obesity and/or osteoporosis in a large American-Caucasian sample (1,873 individuals from 405 nuclear families) by PCR-invader assay. We compared our results with those from the databases and other published studies. Of the 41 SNPs, 8 were monomorphic in our sample. Twelve were reported for the first time for Caucasians and the other 29 SNPs in our sample essentially confirmed the respective allele frequencies for Caucasians in the databases and previous studies. The comparison of our data with other ethnic groups showed significant differentiation between the three major world ethnic groups at some SNPs (Caucasians and Africans differed at 3 of the 18 shared SNPs, and Caucasians and Asians differed at 13 of the 22 shared SNPs). This genetic differentiation may have an important implication for studying the well-known ethnic differences in the prevalence of obesity and osteoporosis, and complex disorders in general.
  
  
  CONCLUSIONS
  A comparative analysis of the SNP data of the candidate genes obtained in the present study, as well as those retrieved from the public domain, suggests that the databases may currently have serious limitations for studying complex disorders with an ethnic-dependent background due to the incomplete and uneven representation of the candidate SNPs in the databases for the major ethnic groups. This conclusion attests to the imperative necessity of large-scale and accurate characterization of these SNPs in different ethnic groups.
authors.affiliation: Osteoporosis Research Center and Department of Biomedical Sciences, Creighton University, 601 N, 30th St, Suite 6730, Omaha, NE 68131, USA. dvornyk@creighton.edu
authors.forename: Volodymyr
authors.initials: V
authors.lastname: Dvornyk
authors.forename: Ji-Rong
authors.initials: JR
authors.lastname: Long
authors.forename: Dong-Hai
authors.initials: DH
authors.lastname: Xiong
authors.forename: Peng-Yuan
authors.initials: PY
authors.lastname: Liu
authors.forename: Lan-Juan
authors.initials: LJ
authors.lastname: Zhao
authors.forename: Hui
authors.initials: H
authors.lastname: Shen
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Zhang
authors.forename: Yong-Jun
authors.initials: YJ
authors.lastname: Liu
authors.forename: Sonia
authors.initials: S
authors.lastname: Rocha-Sanchez
authors.forename: Peng
authors.initials: P
authors.lastname: Xiao
authors.forename: Robert R
authors.initials: RR
authors.lastname: Recker
authors.forename: Hong-Wen
authors.initials: HW
authors.lastname: Deng
mesh_terms: D044466:Asian People / Q000235:genetics; D044383:Black People / Q000235:genetics; D030561:Databases, Nucleic Acid; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics*; D014644:Genetic Variation; D005838:Genotype; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D008297:Male; D009765:Obesity / Q000235:genetics*; D010024:Osteoporosis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D044465:White People / Q000235:genetics