title: Are C-reactive protein associated genetic variants associated with serum levels and retinal markers of microvascular pathology in Asian populations from Singapore?
abstract: BACKGROUND
  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.
authors.affiliation: Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore.
authors.forename: Rajkumar
authors.initials: R
authors.lastname: Dorajoo
authors.forename: Ruoying
authors.initials: R
authors.lastname: Li
authors.forename: Mohammad Kamran
authors.initials: MK
authors.lastname: Ikram
authors.forename: Jianjun
authors.initials: J
authors.lastname: Liu
authors.forename: Philippe
authors.initials: P
authors.lastname: Froguel
authors.forename: Jeannette
authors.initials: J
authors.lastname: Lee
authors.forename: Xueling
authors.initials: X
authors.lastname: Sim
authors.forename: Rick Twee-Hee
authors.initials: RT
authors.lastname: Ong
authors.forename: Wan Ting
authors.initials: WT
authors.lastname: Tay
authors.forename: Chen
authors.initials: C
authors.lastname: Peng
authors.forename: Terri L
authors.initials: TL
authors.lastname: Young
authors.forename: Alexandra I F
authors.initials: AI
authors.lastname: Blakemore
authors.forename: Ching Yu
authors.initials: CY
authors.lastname: Cheng
authors.forename: Tin
authors.initials: T
authors.lastname: Aung
authors.forename: Paul
authors.initials: P
authors.lastname: Mitchell
authors.forename: Jie Jin
authors.initials: JJ
authors.lastname: Wang
authors.forename: Caroline C
authors.initials: CC
authors.lastname: Klaver
authors.forename: Eric
authors.initials: E
authors.lastname: Boerwinkle
authors.forename: Ronald
authors.initials: R
authors.lastname: Klein
authors.forename: David S
authors.initials: DS
authors.lastname: Siscovick
authors.forename: Richard A
authors.initials: RA
authors.lastname: Jensen
authors.forename: Vilmundur
authors.initials: V
authors.lastname: Gudnason
authors.forename: Albert Vernon
authors.initials: AV
authors.lastname: Smith
authors.forename: Yik Ying
authors.initials: YY
authors.lastname: Teo
authors.forename: Tien Yin
authors.initials: TY
authors.lastname: Wong
authors.forename: E-Shyong
authors.initials: ES
authors.lastname: Tai
authors.forename: Chew-Kiat
authors.initials: CK
authors.lastname: Heng
authors.forename: Yechiel
authors.initials: Y
authors.lastname: Friedlander
mesh_terms: D000328:Adult; D001057:Apolipoproteins E / Q000235:genetics; D044466:Asian People; D002097:C-Reactive Protein / Q000235:genetics*; D016207:Cytokines / Q000235:genetics; D005260:Female; D056426:Genetic Loci; D055106:Genome-Wide Association Study; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D055806:Microvessels / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D054411:Receptors, Leptin / Q000235:genetics; D012161:Retinal Artery / Q000378:metabolism* / Q000473:pathology; D012169:Retinal Vein / Q000378:metabolism* / Q000473:pathology; D012846:Singapore; D044465:White People
chemical_list: D001057:Apolipoproteins E; D016207:Cytokines; C496487:HNF1A protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha; D054411:Receptors, Leptin; D002097:C-Reactive Protein