Dataset Information

Novel Genetic Loci Associated With Retinal Microvascular Diameter.

ABSTRACT: BACKGROUND:There is increasing evidence that retinal microvascular diameters are associated with cardiovascular and cerebrovascular conditions. The shared genetic effects of these associations are currently unknown. The aim of this study was to increase our understanding of the genetic factors that mediate retinal vessel size. METHODS AND RESULTS:This study extends previous genome-wide association study results using 24 000+ multiethnic participants from 7 discovery cohorts and 5000+ subjects of European ancestry from 2 replication cohorts. Using the Illumina HumanExome BeadChip, we investigate the association of single-nucleotide polymorphisms and variants collectively across genes with summary measures of retinal vessel diameters, referred to as the central retinal venule equivalent and the central retinal arteriole equivalent. We report 4 new loci associated with central retinal venule equivalent, one of which is also associated with central retinal arteriole equivalent. The 4 single-nucleotide polymorphisms are rs7926971 in TEAD1 (P=3.1×10(-) (11); minor allele frequency=0.43), rs201259422 in TSPAN10 (P=4.4×10(-9); minor allele frequency=0.27), rs5442 in GNB3 (P=7.0×10(-10); minor allele frequency=0.05), and rs1800407 in OCA2 (P=3.4×10(-8); minor allele frequency=0.05). The latter single-nucleotide polymorphism, rs1800407, was also associated with central retinal arteriole equivalent (P=6.5×10(-12)). Results from the gene-based burden tests were null. In phenotype look-ups, single-nucleotide polymorphism rs201255422 was associated with both systolic (P=0.001) and diastolic blood pressures (P=8.3×10(-04)). CONCLUSIONS:Our study expands the understanding of genetic factors influencing the size of the retinal microvasculature. These findings may also provide insight into the relationship between retinal and systemic microvascular disease.

SUBMITTER: Jensen RA

PROVIDER: S-EPMC4758888 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Novel Genetic Loci Associated With Retinal Microvascular Diameter.

Jensen Richard A RA Sim Xueling X Smith Albert Vernon AV Li Xiaohui X Jakobsdóttir Jóhanna J Cheng Ching-Yu CY Brody Jennifer A JA Cotch Mary Frances MF Mcknight Barbara B Klein Ronald R Wang Jie Jin JJ Kifley Annette A Harris Tamara B TB Launer Lenore J LJ Taylor Kent D KD Klein Barbara E K BE Raffel Leslie J LJ Li Xiang X Ikram M Arfan MA Klaver Caroline C CC van der Lee Sven J SJ Mutlu Unal U Hofman Albert A Uitterlinden André G AG Liu Chunyu C Kraja Aldi T AT Mitchell Paul P Gudnason Vilmundur V Rotter Jerome I JI Boerwinkle Eric E van Duijn Cornelia M CM Psaty Bruce M BM Wong Tien Y TY

Circulation. Cardiovascular genetics 20151113 1

<h4>Background</h4>There is increasing evidence that retinal microvascular diameters are associated with cardiovascular and cerebrovascular conditions. The shared genetic effects of these associations are currently unknown. The aim of this study was to increase our understanding of the genetic factors that mediate retinal vessel size.<h4>Methods and results</h4>This study extends previous genome-wide association study results using 24 000+ multiethnic participants from 7 discovery cohorts and 50 ...[more]

PMID: 26567291

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Project description:IntroductionC-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.MethodsGenome-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.ResultsSerum 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).ConclusionsCommon 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.

Dataset Information

Novel Genetic Loci Associated With Retinal Microvascular Diameter.

Publications

Novel Genetic Loci Associated With Retinal Microvascular Diameter.

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