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Four novel Loci (19q13, 6q24, 12q24, and 5q14) influence the microcirculation in vivo.
PLoS Genet. 6:e1001184 (2010)
There is increasing evidence that the microcirculation plays an important role in the pathogenesis of cardiovascular diseases. Changes in retinal vascular caliber reflect early microvascular disease and predict incident cardiovascular events. We performed a genome-wide association study to identify genetic variants associated with retinal vascular caliber. We analyzed data from four population-based discovery cohorts with 15,358 unrelated Caucasian individuals, who are members of the Cohort for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and replicated findings in four independent Caucasian cohorts (n = 6,652). All participants had retinal photography and retinal arteriolar and venular caliber measured from computer software. In the discovery cohorts, 179 single nucleotide polymorphisms (SNP) spread across five loci were significantly associated (p<5.0×10(-8)) with retinal venular caliber, but none showed association with arteriolar caliber. Collectively, these five loci explain 1.0%-3.2% of the variation in retinal venular caliber. Four out of these five loci were confirmed in independent replication samples. In the combined analyses, the top SNPs at each locus were: rs2287921 (19q13; p = 1.61×10(-25), within the RASIP1 locus), rs225717 (6q24; p = 1.25×10(-16), adjacent to the VTA1 and NMBR loci), rs10774625 (12q24; p = 2.15×10(-13), in the region of ATXN2,SH2B3 and PTPN11 loci), and rs17421627 (5q14; p = 7.32×10(-16), adjacent to the MEF2C locus). In two independent samples, locus 12q24 was also associated with coronary heart disease and hypertension. Our population-based genome-wide association study demonstrates four novel loci associated with retinal venular caliber, an endophenotype of the microcirculation associated with clinical cardiovascular disease. These data provide further insights into the contribution and biological mechanisms of microcirculatory changes that underlie cardiovascular disease.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Times Cited
Scopus
Cited By
Cited By
Altmetric
9.543
1.330
97
107
Anmerkungen
Besondere Publikation
Auf Hompepage verbergern
Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
RETINAL VASCULAR CALIBER; GENE/ENVIRONMENT SUSCEPTIBILITY-REYKJAVIK; ANTIHYPERTENSIVE DRUG THERAPIES; GENOME-WIDE ASSOCIATION; VESSEL DIAMETERS; ATHEROSCLEROSIS RISK; CHARGE CONSORTIUM; DISEASE; METAANALYSIS; AGE
Sprache
englisch
Veröffentlichungsjahr
2010
HGF-Berichtsjahr
2011
ISSN (print) / ISBN
1553-7390
e-ISSN
1553-7404
Zeitschrift
PLoS Genetics
Quellenangaben
Band: 6,
Heft: 10,
Artikelnummer: e1001184
Verlag
Public Library of Science (PLoS)
Begutachtungsstatus
Peer reviewed
POF Topic(s)
30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
Forschungsfeld(er)
Genetics and Epidemiology
PSP-Element(e)
G-504100-001
G-500700-001
G-500700-001
PubMed ID
21060863
WOS ID
000283647800015
Erfassungsdatum
2011-07-04