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|Title:||Are C-Reactive Protein Associated Genetic Variants Associated with Serum Levels and Retinal Markers of Microvascular Pathology in Asian Populations from Singapore?||Authors:||Dorajoo, R.
|Issue Date:||2-Jul-2013||Citation:||Dorajoo, R., Li, R., Ikram, M.K., Liu, J., Froguel, P., Lee, J., Sim, X., Ong, R.T.-H., Tay, W.T., Peng, C., Young, T.L., Blakemore, A.I.F., Cheng, C.Y., Aung, T., Mitchell, P., Wang, J.J., Klaver, C.C., Boerwinkle, E., Klein, R., Siscovick, D.S., Jensen, R.A., Gudnason, V., Smith, A.V., Teo, Y.Y., Wong, T.Y., Tai, E.-S., Heng, C.-K., Friedlander, Y. (2013-07-02). Are C-Reactive Protein Associated Genetic Variants Associated with Serum Levels and Retinal Markers of Microvascular Pathology in Asian Populations from Singapore?. PLoS ONE 8 (7) : -. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0067650||Abstract:||Introduction:C-reactive protein (CRP) levels are associated with cardiovascular disease and systemic inflammation. We assessed whether CRP-associated loci were associated with serum CRP and retinal markers of microvascular disease, in Asian populations.Methods:Genome-wide association analysis (GWAS) for serum CRP was performed in East-Asian Chinese (N = 2,434) and Malays (N = 2,542) and South-Asian Indians (N = 2,538) from Singapore. Leveraging on GWAS data, we assessed, in silico, association levels among the Singaporean datasets for 22 recently identified CRP-associated loci. At loci where directional inconsistencies were observed, quantification of inter-ethnic linkage disequilibrium (LD) difference was determined. Next, we assessed association for a variant at CRP and retinal vessel traits [central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE)] in a total of 24,132 subjects of East-Asian, South-Asian and European ancestry.Results:Serum CRP was associated with SNPs in/near APOE, CRP, HNF1A and LEPR (p-values ≤4.7×10-8) after meta-analysis of Singaporean populations. Using a candidate-SNP approach, we further replicated SNPs at 4 additional loci that had been recently identified to be associated with serum CRP (IL6R, GCKR, IL6 and IL1F10) (p-values ≤0.009), in the Singaporean datasets. SNPs from these 8 loci explained 4.05% of variance in serum CRP. Two SNPs (rs2847281 and rs6901250) were detected to be significant (p-value ≤0.036) but with opposite effect directions in the Singaporean populations as compared to original European studies. At these loci we did not detect significant inter-population LD differences. We further did not observe a significant association between CRP variant and CRVE or CRAE levels after meta-analysis of all Singaporean and European datasets (p-value >0.058).Conclusions:Common variants associated with serum CRP, first detected in primarily European studies, are also associated with CRP levels in East-Asian and South-Asian populations. We did not find a causal link between CRP and retinal measures of microvascular disease. © 2013 Dorajoo et al.||Source Title:||PLoS ONE||URI:||http://scholarbank.nus.edu.sg/handle/10635/108193||ISSN:||19326203||DOI:||10.1371/journal.pone.0067650|
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