Functional annotation of sixty-five type-2 diabetes risk SNPs and its application
in risk prediction
#MMPMID28262806
Wu Y
; Jing R
; Dong Y
; Kuang Q
; Li Y
; Huang Z
; Gan W
; Xue Y
; Li Y
; Li M
Sci Rep
2017[Mar]; 7
(?): 43709
PMID28262806
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Genome-wide association studies (GWAS) have identified more than sixty single
nucleotide polymorphisms (SNPs) associated with increased risk for type 2
diabetes (T2D). However, the identification of causal risk SNPs for T2D
pathogenesis was complicated by the factor that each risk SNP is a surrogate for
the hundreds of SNPs, most of which reside in non-coding regions. Here we provide
a comprehensive annotation of 65 known T2D related SNPs and inspect putative
functional SNPs probably causing protein dysfunction, response element
disruptions of known transcription factors related to T2D genes and regulatory
response element disruption of four histone marks in pancreas and pancreas islet.
In new identified risk SNPs, some of them were reported as T2D related SNPs in
recent studies. Further, we found that accumulation of modest effects of single
sites markedly enhanced the risk prediction based on 1989 T2D samples and 3000
healthy controls. The A(ROC) value increased from 0.58 to 0.62 by only using
genotype score when putative risk SNPs were added. Besides, the net
reclassification improvement is 10.03% on the addition of new risk SNPs. Taken
together, functional annotation could provide a list of prioritized potential
risk SNPs for the further estimation on the T2D susceptibility of individuals.
|*Genetic Predisposition to Disease
[MESH]
|*Genome-Wide Association Study
[MESH]
|*Polymorphism, Single Nucleotide
[MESH]
|Computational Biology/methods
[MESH]
|Diabetes Mellitus, Type 2/*genetics/metabolism
[MESH]
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