Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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23776548
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.
DATE PUBLISHED
2013
HISTORY
PUBSTATUS PUBSTATUSDATE
ppublish 2013
received 2013/02/20
accepted 2013/04/19
epublish 2013/06/12
entrez 2013/06/19 06:00
pubmed 2013/06/19 06:00
medline 2014/01/24 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Sim X Sim Xueling X Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, United States of America.
Jensen RA Jensen Richard A RA
Ikram MK Ikram M Kamran MK
Cotch MF Cotch Mary Frances MF
Li X Li Xiaohui X
MacGregor S MacGregor Stuart S
Xie J Xie Jing J
Smith AV Smith Albert Vernon AV
Boerwinkle E Boerwinkle Eric E
Mitchell P Mitchell Paul P
Klein R Klein Ronald R
Klein BE Klein Barbara E K BE
Glazer NL Glazer Nicole L NL
Lumley T Lumley Thomas T
McKnight B McKnight Barbara B
Psaty BM Psaty Bruce M BM
de Jong PT de Jong Paulus T V M PT
Hofman A Hofman Albert A
Rivadeneira F Rivadeneira Fernando F
Uitterlinden AG Uitterlinden Andre G AG
van Duijn CM van Duijn Cornelia M CM
Aspelund T Aspelund Thor T
Eiriksdottir G Eiriksdottir Gudny G
Harris TB Harris Tamara B TB
Jonasson F Jonasson Fridbert F
Launer LJ Launer Lenore J LJ
Wellcome Trust Case Control Consortium 2
Attia J Attia John J
Baird PN Baird Paul N PN
Harrap S Harrap Stephen S
Holliday EG Holliday Elizabeth G EG
Inouye M Inouye Michael M
Rochtchina E Rochtchina Elena E
Scott RJ Scott Rodney J RJ
Viswanathan A Viswanathan Ananth A
Global BPGen Consortium
Li G Li Guo G
Smith NL Smith Nicholas L NL
Wiggins KL Wiggins Kerri L KL
Kuo JZ Kuo Jane Z JZ
Taylor KD Taylor Kent D KD
Hewitt AW Hewitt Alex W AW
Martin NG Martin Nicholas G NG
Montgomery GW Montgomery Grant W GW
Sun C Sun Cong C
Young TL Young Terri L TL
Mackey DA Mackey David A DA
van Zuydam NR van Zuydam Natalie R NR
Doney AS Doney Alex S F AS
Palmer CN Palmer Colin N A CN
Morris AD Morris Andrew D AD
Rotter JI Rotter Jerome I JI
Tai ES Tai E Shyong ES
Gudnason V Gudnason Vilmundur V
Vingerling JR Vingerling Johannes R JR
Siscovick DS Siscovick David S DS
Wang JJ Wang Jie Jin JJ
Wong TY Wong Tien Y TY
INVESTIGATORS
LASTNAME FORENAME INITIALS AFFILIATION
Donnelly Peter P
Barroso Ines I
Blackwell Jenefer M JM
Bramon Elvira E
Brown Matthew A MA
Casas Juan P JP
Corvin Aiden A
Deloukas Panos P
Duncanson Audrey A
Jankowski Janusz J
Markus Hugh S HS
Mathew Christopher G CG
Palmer Colin N A CN
Plomin Robert R
Rautanen Anna A
Sawcer Stephen J SJ
Trembath Richard C RC
Viswanathan Ananth C AC
Wood Nicholas W NW
Spencer Chris C A CC
Band Gavin G
Bellenguez Céline C
Freeman Colin C
Hellenthal Garrett G
Giannoulatou Eleni E
Pirinen Matti M
Pearson Richard R
Strange Amy A
Su Zhan Z
Vukcevic Damjan D
Donnelly Peter P
Langford Cordelia C
Hunt Sarah E SE
Edkins Sarah S
Gwilliam Rhian R
Blackburn Hannah H
Bumpstead Suzannah J SJ
Dronov Serge S
Gillman Matthew M
Gray Emma E
Hammond Naomi N
Jayakumar Alagurevathi A
McCann Owen T OT
Liddle Jennifer J
Potter Simon C SC
Ravindrarajah Radhi R
Ricketts Michelle M
Waller Matthew M
Weston Paul P
Widaa Sara S
Whittaker Pamela P
Barroso Ines I
Deloukas Panos P
Mathew Christopher G C
Blackwell Jenefer M JM
Brown Matthew A MA
Corvin Aiden A
McCarthy Mark I MI
Spencer Chris C A CC
Newton-Cheh Christopher C
Johnson Toby T
Gateva Vesela V
Tobin Martin D MD
Bochud Murielle M
Coin Lachlan L
Najjar Samer S SS
Zhao Jing Hua JH
Heath Simon C SC
Eyheramendy Susana S
Papadakis Konstantinos K
Voight Benjamin F BF
Scott Laura J LJ
Zhang Feng F
Farrall Martin M
Tanaka Toshiko T
Wallace Chris C
Chambers John C JC
Khaw Kay-Tee KT
Nilsson Peter P
van der Harst Pim P
Polidoro Silvia S
Grobbee Diederick E DE
Onland-Moret N Charlotte NC
Bots Michiel L ML
Wain Louise V LV
Elliott Katherine S KS
Teumer Alexander A
Luan Jian'an J
Lucas Gavin G
Kuusisto Johanna J
Burton Paul R PR
Hadley David D
McArdle Wendy L WL
Brown Morris M
Dominiczak Anna A
Newhouse Stephen J SJ
Samani Nilesh J NJ
Webster John J
Zeggini Eleftheria E
Beckmann Jacques S JS
Bergmann Sven S
Lim Noha N
Song Kijoung K
Vollenweider Peter P
Waeber Gerard G
Waterworth Dawn M DM
Yuan Xin X
Groop Leif L
Orho-Melander Marju M
Allione Alessandra A
Di Gregorio Alessandra A
Guarrera Simonetta S
Panico Salvatore S
Ricceri Fulvio F
Romanazzi Valeria V
Sacerdote Carlotta C
Vineis Paolo P
Barroso Inês I
Sandhu Manjinder S MS
Luben Robert N RN
Crawford Gabriel J GJ
Jousilahti Pekka P
Perola Markus M
Boehnke Michael M
Bonnycastle Lori L LL
Collins Francis S FS
Jackson Anne U AU
Mohlke Karen L KL
Stringham Heather M HM
Valle Timo T TT
Willer Cristen J CJ
Bergman Richard N RN
Morken Mario A MA
Döring Angela A
Gieger Christian C
Illig Thomas T
Meitinger Thomas T
Org Elin E
Pfeufer Arne A
Wichmann H Erich HE
Kathiresan Sekar S
Marrugat Jaume J
O'Donnell Christopher J CJ
Schwartz Stephen M SM
Siscovick David S DS
Subirana Isaac I
Freimer Nelson B NB
Hartikainen Anna-Liisa AL
McCarthy Mark I MI
O'Reilly Paul F PF
Peltonen Leena L
Pouta Anneli A
de Jong Paul E PE
Snieder Harold H
van Gilst Wiek H WH
Clarke Robert R
Goel Anuj A
Hamsten Anders A
Peden John F JF
Seedorf Udo U
Syvänen Ann-Christine AC
Tognoni Giovanni G
Lakatta Edward G EG
Sanna Serena S
Scheet Paul P
Schlessinger David D
Scuteri Angelo A
Dörr Marcus M
Ernst Florian F
Felix Stephan B SB
Homuth Georg G
Lorbeer Roberto R
Reffelmann Thorsten T
Rettig Rainer R
Völker Uwe U
Galan Pilar P
Gut Ivo G IG
Hercberg Serge S
Lathrop G Mark GM
Zeleneka Diana D
Deloukas Panos P
Soranzo Nicole N
Williams Frances M FM
Zhai Guangju G
Salomaa Veikko V
Laakso Markku M
Elosua Roberto R
Forouhi Nita G NG
Völzke Henry H
Uiterwaal Cuno S CS
van der Schouw Yvonne T YT
Numans Mattijs E ME
Matullo Giuseppe G
Navis Gerjan G
Berglund Göran G
Bingham Sheila A SA
Kooner Jaspal S JS
Connell John M JM
Bandinelli Stefania S
Ferrucci Luigi L
Watkins Hugh H
Spector Tim D TD
Tuomilehto Jaakko J
Altshuler David D
Strachan David P DP
Laan Maris M
Meneton Pierre P
Wareham Nicholas J NJ
Uda Manuela M
Jarvelin Marjo-Riitta MR
Mooser Vincent V
Melander Olle O
Loos Ruth J F RJ
Elliott Paul P
Abecasis Goncalo R GR
Caulfield Mark M
Munroe Patricia B PB
JOURNAL
VOLUME: 8
ISSUE: 6
TITLE: PloS one
ISOABBREVIATION: PLoS ONE
YEAR: 2013
MONTH:
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1932-6203
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: PLoS One
COUNTRY: United States
ISSNLINKING: 1932-6203
NLMUNIQUEID: 101285081
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GRANTID AGENCY COUNTRY
085475/08/Z Wellcome Trust United Kingdom
085475/B/08/Z Wellcome Trust United Kingdom
090532 Wellcome Trust United Kingdom
1R01EY018246 NEI NIH HHS United States
AG-023269 NIA NIH HHS United States
AG-027058 NIA NIH HHS United States
AG-15928 NIA NIH HHS United States
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DK063491 NIDDK NIH HHS United States
G0801056 Medical Research Council United Kingdom
G1000143 Medical Research Council United Kingdom
HHSN268200625226C PHS HHS United States
HHSN268201100005C PHS HHS United States
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HHSN268201100007C PHS HHS United States
HHSN268201100008C PHS HHS United States
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HHSN268201100012C PHS HHS United States
HL075366 NHLBI NIH HHS United States
HL080295 NHLBI NIH HHS United States
HL087652 NHLBI NIH HHS United States
M01-RR00425 NCRR NIH HHS United States
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N01 HC-55222 NHLBI NIH HHS United States
N01 HC-95159 NHLBI NIH HHS United States
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N01-HC-95163 NHLBI NIH HHS United States
N01-HC-95164 NHLBI NIH HHS United States
N01-HC-95165 NHLBI NIH HHS United States
N01-HC-95166 NHLBI NIH HHS United States
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N01-HC-95168 NHLBI NIH HHS United States
N01-HC-95169 NHLBI NIH HHS United States
N02-HL-6-4278 NHLBI NIH HHS United States
R01 HL073410 NHLBI NIH HHS United States
R01 HL085251 NHLBI NIH HHS United States
R01 HL105756 NHLBI NIH HHS United States
R01HL086694 NHLBI NIH HHS United States
R01HL087641 NHLBI NIH HHS United States
R01HL59367 NHLBI NIH HHS United States
RR-024156 NCRR NIH HHS United States
T32HL007902 NHLBI NIH HHS United States
U01HG004402 NHGRI NIH HHS United States
UL1 TR000124 NCATS NIH HHS United States
UL1RR025005 NCRR 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 EY000403-08 Intramural NIH HHS United States
ZIA EY000403-09 Intramural NIH HHS United States
ZIA EY000403-10 Intramural NIH HHS United States
ZIA EY000403-11 Intramural NIH HHS United States
ZIA EY000403-12 Intramural NIH HHS United States
ZIA EY000426-06 Intramural NIH HHS United States
ZIA EY000426-07 Intramural NIH HHS United States
ZIA EY000426-08 Intramural NIH HHS United States
ZIA EY000426-09 Intramural NIH HHS United States
ZIA EY000426-10 Intramural NIH HHS United States
ZIAAG007380 PHS HHS United States
ZIAEY000401 PHS HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Aged
Aged, 80 and over
Arterioles metabolism
Chromosomes, Human, Pair 5 genetics
European Continental Ancestry Group genetics
Female genetics
Genetic Loci genetics
Genome-Wide Association Study genetics
Genotype genetics
Humans genetics
MEF2 Transcription Factors genetics
Male genetics
Microcirculation genetics
Middle Aged genetics
Models, Genetic genetics
Retinal Vessels metabolism
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 MEF2 Transcription Factors
0 MEF2C protein, human
OTHER ID's
OTHERID SOURCE
PMC3680438 NLM