title: Genetic loci for retinal arteriolar microcirculation.
abstract: Narrow arterioles in the retina have been shown to predict hypertension as well as other vascular diseases, likely through an increase in the peripheral resistance of the microcirculatory flow. In this study, we performed a genome-wide association study in 18,722 unrelated individuals of European ancestry from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium and the Blue Mountain Eye Study, to identify genetic determinants associated with variations in retinal arteriolar caliber. Retinal vascular calibers were measured on digitized retinal photographs using a standardized protocol. One variant (rs2194025 on chromosome 5q14 near the myocyte enhancer factor 2C MEF2C gene) was associated with retinal arteriolar caliber in the meta-analysis of the discovery cohorts at genome-wide significance of P-value <5×10(-8). This variant was replicated in an additional 3,939 individuals of European ancestry from the Australian Twins Study and Multi-Ethnic Study of Atherosclerosis (rs2194025, P-value = 2.11×10(-12) in combined meta-analysis of discovery and replication cohorts). In independent studies of modest sample sizes, no significant association was found between this variant and clinical outcomes including coronary artery disease, stroke, myocardial infarction or hypertension. In conclusion, we found one novel loci which underlie genetic variation in microvasculature which may be relevant to vascular disease. The relevance of these findings to clinical outcomes remains to be determined.
authors.affiliation: Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, United States of America.
authors.forename: Xueling
authors.initials: X
authors.lastname: Sim
authors.forename: Richard A
authors.initials: RA
authors.lastname: Jensen
authors.forename: M Kamran
authors.initials: MK
authors.lastname: Ikram
authors.forename: Mary Frances
authors.initials: MF
authors.lastname: Cotch
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Li
authors.forename: Stuart
authors.initials: S
authors.lastname: MacGregor
authors.forename: Jing
authors.initials: J
authors.lastname: Xie
authors.forename: Albert Vernon
authors.initials: AV
authors.lastname: Smith
authors.forename: Eric
authors.initials: E
authors.lastname: Boerwinkle
authors.forename: Paul
authors.initials: P
authors.lastname: Mitchell
authors.forename: Ronald
authors.initials: R
authors.lastname: Klein
authors.forename: Barbara E K
authors.initials: BE
authors.lastname: Klein
authors.forename: Nicole L
authors.initials: NL
authors.lastname: Glazer
authors.forename: Thomas
authors.initials: T
authors.lastname: Lumley
authors.forename: Barbara
authors.initials: B
authors.lastname: McKnight
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Psaty
authors.forename: Paulus T V M
authors.initials: PT
authors.lastname: de Jong
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.forename: Fernando
authors.initials: F
authors.lastname: Rivadeneira
authors.forename: Andre G
authors.initials: AG
authors.lastname: Uitterlinden
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: van Duijn
authors.forename: Thor
authors.initials: T
authors.lastname: Aspelund
authors.forename: Gudny
authors.initials: G
authors.lastname: Eiriksdottir
authors.forename: Tamara B
authors.initials: TB
authors.lastname: Harris
authors.forename: Fridbert
authors.initials: F
authors.lastname: Jonasson
authors.forename: Lenore J
authors.initials: LJ
authors.lastname: Launer
authors.forename: John
authors.initials: J
authors.lastname: Attia
authors.forename: Paul N
authors.initials: PN
authors.lastname: Baird
authors.forename: Stephen
authors.initials: S
authors.lastname: Harrap
authors.forename: Elizabeth G
authors.initials: EG
authors.lastname: Holliday
authors.forename: Michael
authors.initials: M
authors.lastname: Inouye
authors.forename: Elena
authors.initials: E
authors.lastname: Rochtchina
authors.forename: Rodney J
authors.initials: RJ
authors.lastname: Scott
authors.forename: Ananth
authors.initials: A
authors.lastname: Viswanathan
authors.forename: Guo
authors.initials: G
authors.lastname: Li
authors.forename: Nicholas L
authors.initials: NL
authors.lastname: Smith
authors.forename: Kerri L
authors.initials: KL
authors.lastname: Wiggins
authors.forename: Jane Z
authors.initials: JZ
authors.lastname: Kuo
authors.forename: Kent D
authors.initials: KD
authors.lastname: Taylor
authors.forename: Alex W
authors.initials: AW
authors.lastname: Hewitt
authors.forename: Nicholas G
authors.initials: NG
authors.lastname: Martin
authors.forename: Grant W
authors.initials: GW
authors.lastname: Montgomery
authors.forename: Cong
authors.initials: C
authors.lastname: Sun
authors.forename: Terri L
authors.initials: TL
authors.lastname: Young
authors.forename: David A
authors.initials: DA
authors.lastname: Mackey
authors.forename: Natalie R
authors.initials: NR
authors.lastname: van Zuydam
authors.forename: Alex S F
authors.initials: AS
authors.lastname: Doney
authors.forename: Colin N A
authors.initials: CN
authors.lastname: Palmer
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Morris
authors.forename: Jerome I
authors.initials: JI
authors.lastname: Rotter
authors.forename: E Shyong
authors.initials: ES
authors.lastname: Tai
authors.forename: Vilmundur
authors.initials: V
authors.lastname: Gudnason
authors.forename: Johannes R
authors.initials: JR
authors.lastname: Vingerling
authors.forename: David S
authors.initials: DS
authors.lastname: Siscovick
authors.forename: Jie Jin
authors.initials: JJ
authors.lastname: Wang
authors.forename: Tien Y
authors.initials: TY
authors.lastname: Wong
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001160:Arterioles / Q000378:metabolism*; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D005260:Female; D056426:Genetic Loci / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D064326:MEF2 Transcription Factors / Q000235:genetics; D008297:Male; D008833:Microcirculation / Q000235:genetics*; D008875:Middle Aged; D008957:Models, Genetic; D012171:Retinal Vessels / Q000378:metabolism*; D044465:White People / Q000235:genetics
chemical_list: D064326:MEF2 Transcription Factors; C578040:MEF2C protein, human