Dataset Information

Are C-reactive protein associated genetic variants associated with serum levels and retinal markers of microvascular pathology in Asian populations from Singapore?

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.

SUBMITTER: Dorajoo R

PROVIDER: S-EPMC3699653 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Publications

Are C-reactive protein associated genetic variants associated with serum levels and retinal markers of microvascular pathology in Asian populations from Singapore?

Dorajoo Rajkumar R Li Ruoying R Ikram Mohammad Kamran MK Liu Jianjun J Froguel Philippe P Lee Jeannette J Sim Xueling X Ong Rick Twee-Hee RT Tay Wan Ting WT Peng Chen C Young Terri L TL Blakemore Alexandra I F AI Cheng Ching Yu CY Aung Tin T Mitchell Paul P Wang Jie Jin JJ Klaver Caroline C CC Boerwinkle Eric E Klein Ronald R Siscovick David S DS Jensen Richard A RA Gudnason Vilmundur V Smith Albert Vernon AV Teo Yik Ying YY Wong Tien Yin TY Tai E-Shyong ES Heng Chew-Kiat CK Friedlander Yechiel Y

PloS one 20130702 7

<h4>Introduction</h4>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.<h4>Methods</h4>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 silic ...[more]

PMID: 23844046

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Project description:PurposeFor OCT retinal thickness measurements to be used as a prodromal age-related macular degeneration (AMD) risk marker, the 3-dimensional (3D) topographic variation of the relationship between genetic susceptibility to AMD and retinal thickness needs to be assessed. We aimed to evaluate individual retinal layer thickness changes and topography at the macula that are associated with AMD genetic susceptibility.DesignGenetic association study.ParticipantsA total of 1579 healthy participants (782 Chinese, 353 Malays, and 444 Indians) from the multiethnic Singapore Epidemiology of Eye Diseases study were included.MethodsSpectral-domain OCT and automatic segmentation of individual retinal layers were performed to produce 10 retinal layer thickness measurements at each ETDRS subfield, producing 3D topographic information. Age-related macular degeneration genetic susceptibility was represented via single nucleotide polymorphisms (SNPs) and aggregated via whole genome (overall) and pathway-specific age-related macular degeneration polygenic risk score (PRSAMD).Main outcome measuresAssociations of individual SNPs, overall PRSAMD, and pathway-specific PRSAMD with retinal thickness were analyzed by individual retinal layer and ETDRS subfield.ResultsCFH rs10922109, ARMS2-HTRA1 rs3750846, and LIPC rs2043085 were the top AMD susceptibility SNPs associated with retinal thickness of individual layers (P < 1.67 × 10-3), all at the central subfield. The overall PRSAMD was most associated with thinner L9 (outer segment photoreceptor/retinal pigment epithelium complex) thickness at the central subfield (β = -0.63 μm; P = 5.45 × 10-9). Pathway-specific PRSAMD for the complement cascade (β = -0.53 μm; P = 9.42 × 10-7) and lipoprotein metabolism (β = -0.05 μm; P = 0.0061) were associated with thinner photoreceptor layers (L9 and L7 [photoreceptor inner/outer segments], respectively) at the central subfield. The mean PRSAMD score was larger among Indians compared with that of the Chinese and had the thinnest thickness at the L9 central subfield (β = -1.00 μm; P = 2.91 × 10-7; R2 = 5.5%). Associations at other retinal layers and ETDRS regions were more heterogeneous.ConclusionsOverall genetic susceptibility to AMD and the aggregate effects of the complement cascade and lipoprotein metabolism pathway are associated most significantly with L7 and L9 photoreceptor thinning at the central macula in healthy individuals. Photoreceptor thinning has potential to be a prodromal AMD risk marker, and topographic variation should be considered.Financial disclosuresProprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Dataset Information

Are C-reactive protein associated genetic variants associated with serum levels and retinal markers of microvascular pathology in Asian populations from Singapore?

Introduction

Methods

Results

Conclusions

Publications

Are C-reactive protein associated genetic variants associated with serum levels and retinal markers of microvascular pathology in Asian populations from Singapore?

Similar Datasets

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