Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore.
PLoS One. 2013 Jul 2;8(7):e67650. doi: 10.1371/journal.pone.0067650. Print 2013.
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.
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.
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).
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.
C 反应蛋白（CRP）水平与心血管疾病和全身炎症有关。我们评估了 CRP 相关基因座是否与亚洲人群的血清 CRP 和视网膜微血管疾病标志物有关。
对来自新加坡的东亚华人（N=2434）和马来人（N=2542）以及南亚印度人（N=2538）进行了血清 CRP 的全基因组关联分析（GWAS）。利用 GWAS 数据，我们在新加坡数据集之间评估了 22 个最近确定的与 CRP 相关的基因座的关联水平。在观察到方向不一致的基因座，确定了不同种族之间的连锁不平衡（LD）差异的定量。接下来，我们评估了 CRP 变体与视网膜血管特征[中心视网膜动脉当量（CRAE）和中心视网膜静脉当量（CRVE）]之间的关联，共纳入了东亚、南亚和欧洲血统的 24132 名受试者。
在新加坡人群的荟萃分析中，血清 CRP 与 APOE、CRP、HNF1A 和 LEPR 中的 SNP 相关（p 值≤4.7×10（-8））。使用候选 SNP 方法，我们在新加坡数据集进一步复制了最近确定与血清 CRP 相关的另外 4 个基因座的 SNP（IL6R、GCKR、IL6 和 IL1F10）（p 值≤0.009）。这些基因座的 SNP 解释了血清 CRP 变异的 4.05%。在新加坡人群中，检测到 2 个 SNP（rs2847281 和 rs6901250）具有显著意义（p 值≤0.036），但与原始欧洲研究的作用方向相反。在这些基因座中，我们没有检测到人群间显著的 LD 差异。在对所有新加坡和欧洲数据集进行荟萃分析后，我们没有观察到 CRP 变体与 CRVE 或 CRAE 水平之间存在显著关联（p 值>0.058）。
首先在主要的欧洲研究中发现的与血清 CRP 相关的常见变异也与东亚和南亚人群的 CRP 水平相关。我们没有发现 CRP 与视网膜微血管疾病的衡量指标之间存在因果关系。
