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Genetic loci for retinal arteriolar microcirculation.

Thursday,2013-09-12 13:13 America/Los_Angeles — eenright
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
ZIA EY000401-13 / / Intramural NIH HHS / United States
N01-HC-95162 / HC / NHLBI NIH HHS / United States
G0801056 / / Medical Research Council / United Kingdom
Z01 EY000426-05 / / Intramural NIH HHS / United States
Z99 EY999999 / / Intramural NIH HHS / United States
N01-HC-85085 / HC / NHLBI NIH HHS / United States
R01HL59367 / HL / NHLBI NIH HHS / United States
1R01EY018246 / EY / NEI NIH HHS / United States
ZIA EY000401-11 / / Intramural NIH HHS / United States
ZIA EY000403-13 / / Intramural NIH HHS / United States
ZIA EY000426-10 / / Intramural NIH HHS / United States
N01-HC-85081 / HC / NHLBI NIH HHS / United States
HHSN268201100005C / / PHS HHS / United States
RR-024156 / RR / NCRR NIH HHS / United States
N01-HC-95163 / HC / NHLBI NIH HHS / United States
R01 HL085251 / HL / NHLBI NIH HHS / United States
ZIAEY000401 / / PHS HHS / United States
N01-HC-95168 / HC / NHLBI NIH HHS / United States
ZIA EY000426-13 / / Intramural NIH HHS / United States
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
ZIA EY000401-08 / / Intramural NIH HHS / United States
G1000143 / / Medical Research Council / United Kingdom
AG-20098 / AG / NIA NIH HHS / United States
HHSN268200625226C / / PHS HHS / United States
T32HL007902 / HL / NHLBI NIH HHS / United States
N01-HC-95165 / HC / NHLBI NIH HHS / United States
ZIA EY000403-11 / / Intramural NIH HHS / United States
HL087652 / HL / NHLBI NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
ZIA EY000401-12 / / Intramural NIH HHS / United States
N01-HC-85086 / HC / NHLBI NIH HHS / United States
Z01 EY000426-04 / / Intramural NIH HHS / United States
ZIAAG007380 / / PHS HHS / United States
HHSN268201100010C / / PHS HHS / United States
R01 HL105756 / HL / NHLBI NIH HHS / United States
U01HG004402 / HG / NHGRI NIH HHS / United States
AG-027058 / AG / NIA NIH HHS / United States
ZIA EY000426-11 / / Intramural NIH HHS / United States
N01-HC-85082 / HC / NHLBI NIH HHS / United States
ZIA EY000403-10 / / Intramural NIH HHS / United States
AG-023269 / AG / NIA NIH HHS / United States
HL075366 / HL / NHLBI NIH HHS / United States
N01-HC-35129 / HC / NHLBI NIH HHS / United States
N01 HC-55222 / HC / NHLBI NIH HHS / United States
HHSN268201100008C / / PHS HHS / United States
HHSN268201100012C / / PHS HHS / United States
R01HL087641 / HL / NHLBI NIH HHS / United States
N01 HC-95159 / HC / NHLBI NIH HHS / United States
N01-HC-95169 / HC / NHLBI NIH HHS / United States
ZIA EY000403-09 / / Intramural NIH HHS / United States
G0401527 / / Medical Research Council / United Kingdom
N01-HC-95164 / HC / NHLBI NIH HHS / United States
Z01 EY000403-06 / / Intramural NIH HHS / United States
N01-HC-85083 / HC / NHLBI NIH HHS / United States
090532 / / Wellcome Trust / United Kingdom
N01-HC-75150 / HC / NHLBI NIH HHS / United States
ZIA EY000403-08 / / Intramural NIH HHS / United States
N01-HC-85080 / HC / NHLBI NIH HHS / United States
N01-HC-95160 / HC / NHLBI NIH HHS / United States
N01 HC-15103 / HC / NHLBI NIH HHS / United States
ZIA EY000401-15 / / Intramural NIH HHS / United States
Z01 EY000403-07 / / Intramural NIH HHS / United States
Z01 EY000401-06 / / Intramural NIH HHS / United States
085475/B/08/Z / / Wellcome Trust / United Kingdom
HHSN268201100007C / / PHS HHS / United States
ZIA EY000426-09 / / Intramural NIH HHS / United States
ZIA EY000426-07 / / Intramural NIH HHS / United States
ZIA EY000426-12 / / Intramural NIH HHS / United States
N01-AG-12100 / AG / NIA NIH HHS / United States
HHSN268201100011C / / PHS HHS / United States
DK063491 / DK / NIDDK NIH HHS / United States
N01-HC-45133 / HC / NHLBI NIH HHS / United States
N01-HC-85079 / HC / NHLBI NIH HHS / United States
N01-HC-95161 / HC / NHLBI NIH HHS / United States
/ / Wellcome Trust / United Kingdom
ZIA EY000426-06 / / Intramural NIH HHS / United States
HL080295 / HL / NHLBI NIH HHS / United States
N01-HC-85239 / HC / NHLBI NIH HHS / United States
HHSN268201100006C / / PHS HHS / United States
ZIA EY000403-15 / / Intramural NIH HHS / United States
N01-HC-95166 / HC / NHLBI NIH HHS / United States
R01 HL073410 / HL / NHLBI NIH HHS / United States
ZIA EY000401-14 / / Intramural NIH HHS / United States
Z01 EY000401-07 / / Intramural NIH HHS / United States
N01-HC-85084 / HC / NHLBI NIH HHS / United States
ZIA EY000401-10 / / Intramural NIH HHS / United States
ZIA EY000403-12 / / Intramural NIH HHS / United States
N01-HC-95167 / HC / NHLBI NIH HHS / United States
R01HL086694 / HL / NHLBI NIH HHS / United States

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