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Novel Genetic Loci Associated With Retinal Microvascular Diameter.

Monday,2015-12-07 11:41 America/Los_Angeles — zdrager
TitleNovel Genetic Loci Associated With Retinal Microvascular Diameter.
Publication TypeJournal Article
Year of Publication2016
AuthorsJensen, RA, Sim, X, Smith, AVernon, Li, X, Jakobsdottir, J, Cheng, C-Y, Brody, JA, Cotch, MFrances, McKnight, B, Klein, R, Wang, JJin, Kifley, A, Harris, TB, Launer, LJ, Taylor, KD, Klein, BEK, Raffel, LJ, Li, X, Ikram, AM, Klaver, CC, van der Lee, SJ, Mutlu, U, Hofman, A, Uitterlinden, AG, Liu, C, Kraja, AT, Mitchell, P, Gudnason, V, Rotter, JI, Boerwinkle, E, van Duijn, CM, Psaty, BM, Wong, TY
Corporate/Institutional AuthorsCHARGE Exome Chip Blood Pressure Consortium
JournalCirc Cardiovasc Genet
Volume9
Issue1
Pagination45-54
Date Published2016 Feb
ISSN1942-3268
Abstract<p><b>BACKGROUND: </b>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.</p><p><b>METHODS AND RESULTS: </b>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)).</p><p><b>CONCLUSIONS: </b>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.</p>
DOI10.1161/CIRCGENETICS.115.001142
Alternate JournalCirc Cardiovasc Genet
PubMed ID26567291
PubMed Central IDPMC4758888
Grant List5RC2HL102419 / HL / NHLBI NIH HHS / United States
AG023629 / AG / NIA NIH HHS / United States
DK063491 / DK / NIDDK NIH HHS / United States
HHSN268200625226C / / PHS HHS / United States
HHSN268200800007C / HL / NHLBI NIH HHS / United States
HHSN268200800007C / / PHS HHS / United States
HHSN268201100005C / HL / NHLBI NIH HHS / United States
HHSN268201100005C / / PHS HHS / United States
HHSN268201100006C / HL / NHLBI NIH HHS / United States
HHSN268201100006C / / PHS HHS / United States
HHSN268201100007C / HL / NHLBI NIH HHS / United States
HHSN268201100007C / / PHS HHS / United States
HHSN268201100008C / HL / NHLBI NIH HHS / United States
HHSN268201100008C / / PHS HHS / United States
HHSN268201100009C / HL / NHLBI NIH HHS / United States
HHSN268201100009C / / PHS HHS / United States
HHSN268201100010C / HL / NHLBI NIH HHS / United States
HHSN268201100010C / / PHS HHS / United States
HHSN268201100011C / HL / NHLBI NIH HHS / United States
HHSN268201100011C / / PHS HHS / United States
HHSN268201100012C / HL / NHLBI NIH HHS / United States
HHSN268201100012C / / PHS HHS / United States
HHSN268201200036C / HL / NHLBI NIH HHS / United States
HHSN268201200036C / / PHS HHS / United States
HL068986 / HL / NHLBI NIH HHS / United States
HL071205 / HL / NHLBI NIH HHS / United States
HL080295 / HL / NHLBI NIH HHS / United States
HL087652 / HL / NHLBI NIH HHS / United States
HL103612 / HL / NHLBI NIH HHS / United States
HL105756 / HL / NHLBI NIH HHS / United States
HL120393 / HL / NHLBI NIH HHS / United States
N01 HC075150 / HC / NHLBI NIH HHS / United States
N01 HC095159 / HC / NHLBI NIH HHS / United States
N01 HC095160 / HC / NHLBI NIH HHS / United States
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P30 DK063491 / DK / NIDDK NIH HHS / United States
R01 AG023629 / AG / NIA NIH HHS / United States
R01 HL059367 / HL / NHLBI NIH HHS / United States
R01 HL071205 / HL / NHLBI NIH HHS / United States
R01 HL086694 / HL / NHLBI NIH HHS / United States
R01 HL087641 / HL / NHLBI NIH HHS / United States
R01 HL087652 / HL / NHLBI NIH HHS / United States
R01 HL103612 / HL / NHLBI NIH HHS / United States
R01 HL105756 / HL / NHLBI NIH HHS / United States
R01 HL120393 / HL / NHLBI NIH HHS / United States
R01HL086694 / HL / NHLBI NIH HHS / United States
R01HL087641 / HL / NHLBI NIH HHS / United States
R01HL59367 / HL / NHLBI NIH HHS / United States
RC2 HL102419 / HL / NHLBI NIH HHS / United States
U01 HG004402 / HG / NHGRI NIH HHS / United States
U01 HL080295 / HL / NHLBI NIH HHS / United States
U01HG004402 / HG / NHGRI NIH HHS / United States
U01HL080295 / HL / NHLBI NIH HHS / United States
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UL1TR000124 / TR / NCATS NIH HHS / United States
Z01 AG007380-02 / / Intramural NIH HHS / United States
Z01 EY000401-06 / / Intramural NIH HHS / United States
Z01 EY000401-07 / / Intramural NIH HHS / United States
Z99 EY999999 / / Intramural NIH HHS / United States
ZIA EY000401-08 / / Intramural NIH HHS / United States
ZIA EY000401-09 / / Intramural NIH HHS / United States
ZIA EY000401-10 / / Intramural NIH HHS / United States
ZIA EY000401-11 / / Intramural NIH HHS / United States
ZIA EY000401-12 / / Intramural NIH HHS / United States
ZIA EY000401-13 / / Intramural NIH HHS / United States
ZIA EY000401-14 / / Intramural NIH HHS / United States
ZIAAG007380 / / PHS HHS / United States
ZIAEY00401 / / PHS HHS / United States

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