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Genetic loci for retinal arteriolar microcirculation.

TitleGenetic loci for retinal arteriolar microcirculation.
Publication TypeJournal Article
Year of Publication2013
AuthorsSim, X, Jensen, RA, M Ikram, K, Cotch, MFrances, Li, X, Macgregor, S, Xie, J, Smith, AVernon, Boerwinkle, E, Mitchell, P, Klein, R, Klein, BEK, Glazer, NL, Lumley, T, McKnight, B, Psaty, BM, de Jong, PTVM, Hofman, A, Rivadeneira, F, Uitterlinden, AG, van Duijn, CM, Aspelund, T, Eiriksdottir, G, Harris, TB, Jonasson, F, Launer, LJ, Attia, J, Baird, PN, Harrap, S, Holliday, EG, Inouye, M, Rochtchina, E, Scott, RJ, Viswanathan, A, Li, G, Smith, NL, Wiggins, KL, Kuo, JZ, Taylor, KD, Hewitt, AW, Martin, NG, Montgomery, GW, Sun, C, Young, TL, Mackey, DA, van Zuydam, NR, Doney, ASF, Palmer, CNA, Morris, AD, Rotter, JI, Tai, SE, Gudnason, V, Vingerling, JR, Siscovick, DS, Wang, JJin, Wong, TY
Corporate/Institutional AuthorsWellcome Trust Case Control Consortium 2,, Global BPgen Consortium
JournalPLoS One
Volume8
Issue6
Paginatione65804
Date Published2013
ISSN1932-6203
KeywordsAged, Aged, 80 and over, Arterioles, Chromosomes, Human, Pair 5, European Continental Ancestry Group, Female, Genetic Loci, Genome-Wide Association Study, Genotype, Humans, Male, MEF2 Transcription Factors, Microcirculation, Middle Aged, Models, Genetic, Retinal Vessels
Abstract<p>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.</p>
DOI10.1371/journal.pone.0065804
Alternate JournalPLoS ONE
PubMed ID23776548
PubMed Central IDPMC3680438
Grant ListM01-RR00425 / RR / NCRR NIH HHS / United States
UL1RR025005 / RR / NCRR NIH HHS / United States
N02-HL-6-4278 / HL / NHLBI NIH HHS / United States
ZIA EY000401-09 / / Intramural NIH HHS / United States
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N01-HC-95162 / HC / NHLBI NIH HHS / United States
G0801056 / / Medical Research Council / United Kingdom
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N01-HC-85081 / HC / NHLBI NIH HHS / United States
HHSN268201100005C / / PHS HHS / United States
RR-024156 / RR / NCRR NIH HHS / United States
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AG-15928 / AG / NIA NIH HHS / United States
085475/08/Z / / Wellcome Trust / United Kingdom
HHSN268201100009C / / PHS HHS / United States
ZIA EY000403-14 / / Intramural NIH HHS / United States
ZIA EY000426-08 / / Intramural NIH HHS / United States
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G1000143 / / Medical Research Council / United Kingdom
AG-20098 / AG / NIA NIH HHS / United States
HHSN268200625226C / / PHS HHS / United States
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/ / Wellcome Trust / United Kingdom
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R01HL086694 / HL / NHLBI NIH HHS / United States