Current limitations of SNP data from the public domain for studies of complex disorders: a test for ten candidate genes for obesity and osteoporosis. BMC Genet 2004 Feb 25;5:4
Date
04/29/2004Pubmed ID
15113403Pubmed Central ID
PMC395827DOI
10.1186/1471-2156-5-4Scopus ID
2-s2.0-2442684156 (requires institutional sign-in at Scopus site) 34 CitationsAbstract
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.
CONCLUSION: 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.
Author List
Dvornyk V, Long JR, Xiong DH, Liu PY, Zhao LJ, Shen H, Zhang YY, Liu YJ, Rocha-Sanchez S, Xiao P, Recker RR, Deng HWMESH terms used to index this publication - Major topics in bold
Databases, Nucleic AcidFamily Health
Female
Gene Frequency
Genetic Predisposition to Disease
Genetic Variation
Genotype
Humans
Male
Obesity
Osteoporosis
Polymorphism, Single Nucleotide
