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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21060863
TITLE
Four novel Loci (19q13, 6q24, 12q24, and 5q14) influence the microcirculation in vivo.
ABSTRACT
There is increasing evidence that the microcirculation plays an important role in the pathogenesis of cardiovascular diseases. Changes in retinal vascular caliber reflect early microvascular disease and predict incident cardiovascular events. We performed a genome-wide association study to identify genetic variants associated with retinal vascular caliber. We analyzed data from four population-based discovery cohorts with 15,358 unrelated Caucasian individuals, who are members of the Cohort for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and replicated findings in four independent Caucasian cohorts (n  =  6,652). All participants had retinal photography and retinal arteriolar and venular caliber measured from computer software. In the discovery cohorts, 179 single nucleotide polymorphisms (SNP) spread across five loci were significantly associated (p<5.0×10(-8)) with retinal venular caliber, but none showed association with arteriolar caliber. Collectively, these five loci explain 1.0%-3.2% of the variation in retinal venular caliber. Four out of these five loci were confirmed in independent replication samples. In the combined analyses, the top SNPs at each locus were: rs2287921 (19q13; p  =  1.61×10(-25), within the RASIP1 locus), rs225717 (6q24; p = 1.25×10(-16), adjacent to the VTA1 and NMBR loci), rs10774625 (12q24; p  =  2.15×10(-13), in the region of ATXN2,SH2B3 and PTPN11 loci), and rs17421627 (5q14; p = 7.32×10(-16), adjacent to the MEF2C locus). In two independent samples, locus 12q24 was also associated with coronary heart disease and hypertension. Our population-based genome-wide association study demonstrates four novel loci associated with retinal venular caliber, an endophenotype of the microcirculation associated with clinical cardiovascular disease. These data provide further insights into the contribution and biological mechanisms of microcirculatory changes that underlie cardiovascular disease.
DATE PUBLISHED
2010 Oct
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2010/04/26
accepted 2010/09/28
epublish 2010/10/28
entrez 2010/11/10 06:00
pubmed 2010/11/10 06:00
medline 2011/03/08 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Ikram MK Ikram M Kamran MK Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
Sim X Sim Xueling X
Xueling S Xueling Sim S
Jensen RA Jensen Richard A RA
Cotch MF Cotch Mary Frances MF
Hewitt AW Hewitt Alex W AW
Ikram MA Ikram M Arfan MA
Wang JJ Wang Jie Jin JJ
Klein R Klein Ronald R
Klein BE Klein Barbara E K BE
Breteler MM Breteler Monique M B MM
Cheung N Cheung Ning N
Liew G Liew Gerald G
Mitchell P Mitchell Paul P
Uitterlinden AG Uitterlinden Andre G AG
Rivadeneira F Rivadeneira Fernando F
Hofman A Hofman Albert A
de Jong PT de Jong Paulus T V M PT
van Duijn CM van Duijn Cornelia M CM
Kao L Kao Linda L
Cheng CY Cheng Ching-Yu CY
Smith AV Smith Albert Vernon AV
Glazer NL Glazer Nicole L NL
Lumley T Lumley Thomas T
McKnight B McKnight Barbara B
Psaty BM Psaty Bruce M BM
Jonasson F Jonasson Fridbert F
Eiriksdottir G Eiriksdottir Gudny G
Aspelund T Aspelund Thor T
Global BPgen Consortium
Harris TB Harris Tamara B TB
Launer LJ Launer Lenore J LJ
Taylor KD Taylor Kent D KD
Li X Li Xiaohui X
Iyengar SK Iyengar Sudha K SK
Xi Q Xi Quansheng Q
Sivakumaran TA Sivakumaran Theru A TA
Mackey DA Mackey David A DA
Macgregor S Macgregor Stuart S
Martin NG Martin Nicholas G NG
Young TL Young Terri L TL
Bis JC Bis Josh C JC
Wiggins KL Wiggins Kerri L KL
Heckbert SR Heckbert Susan R SR
Hammond CJ Hammond Christopher J CJ
Andrew T Andrew Toby T
Fahy S Fahy Samantha S
Attia J Attia John J
Holliday EG Holliday Elizabeth G EG
Scott RJ Scott Rodney J RJ
Islam FM Islam F M Amirul FM
Rotter JI Rotter Jerome I JI
McAuley AK McAuley Annie K AK
Boerwinkle E Boerwinkle Eric E
Tai ES Tai E Shyong ES
Gudnason V Gudnason Vilmundur V
Siscovick DS Siscovick David S DS
Vingerling JR Vingerling Johannes R JR
Wong TY Wong Tien Y TY
INVESTIGATORS
LASTNAME FORENAME INITIALS AFFILIATION
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 Inîs 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 Gonçalo R GR
Caulfield Mark M
Munroe Patricia B PB
JOURNAL
VOLUME: 6
ISSUE: 10
TITLE: PLoS genetics
ISOABBREVIATION: PLoS Genet.
YEAR: 2010
MONTH: Oct
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1553-7404
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: PLoS Genet
COUNTRY: United States
ISSNLINKING: 1553-7390
NLMUNIQUEID: 101239074
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
Cites Nat Genet. 2009 Jun;41(6):666-76 19430483
Cites Ophthalmology. 1999 Dec;106(12):2269-80 10599656
Cites N Engl J Med. 2000 Jun 15;342(24):1786-90 10853001
Cites Arch Intern Med. 2001 Jan 8;161(1):37-43 11146696
Cites JAMA. 2002 May 15;287(19):2528-33 12020333
Cites Exp Eye Res. 2002 Jul;75(1):69-75 12123638
Cites Curr Eye Res. 2003 Sep;27(3):143-9 14562179
Cites Ann Intern Med. 2004 Feb 17;140(4):248-55 14970147
Cites Invest Ophthalmol Vis Sci. 2004 Jul;45(7):2129-34 15223786
Cites Am J Epidemiol. 1989 Apr;129(4):687-702 2646917
Cites Ann Epidemiol. 1991 Feb;1(3):263-76 1669507
Cites JAMA. 1995 Aug 23-30;274(8):620-5 7637142
Cites Hum Reprod. 1997 Sep;12(9):1851-63 9363696
Cites Cardiovasc Res. 1998 Jun;38(3):814-21 9747450
Cites N Engl J Med. 2004 Nov 25;351(22):2310-7 15564546
Cites Am J Physiol Gastrointest Liver Physiol. 2005 Apr;288(4):G718-28 15528253
Cites Mol Cell Biol. 2005 May;25(9):3575-82 15831463
Cites Brain. 2006 Jan;129(Pt 1):182-8 16317022
Cites Nat Rev Genet. 2006 Mar;7(3):163-73 16462853
Cites Hypertension. 2006 Apr;47(4):797-802 16505201
Cites Hypertension. 2006 Apr;47(4):644-5 16505202
Cites Invest Ophthalmol Vis Sci. 2006 Jun;47(6):2341-50 16723443
Cites Am J Epidemiol. 2007 Jan 1;165(1):78-84 17041135
Cites N Engl J Med. 2007 Feb 22;356(8):830-40 17314342
Cites Am J Epidemiol. 2007 May 1;165(9):1076-87 17351290
Cites Nature. 2007 Jun 7;447(7145):661-78 17554300
Cites Arch Ophthalmol. 2007 Jun;125(6):813-8 17562993
Cites Invest Ophthalmol Vis Sci. 2007 Jul;48(7):3014-8 17591866
Cites Ophthalmology. 2007 Oct;114(10):1884-92 17540447
Cites Dev Cell. 2008 Jan;14(1):37-49 18194651
Cites Genet Epidemiol. 2008 Feb;32(2):179-85 18200594
Cites Diabetes Care. 2008 Mar;31(3):544-9 18070990
Cites Diabetes. 2008 Jun;57(6):1645-50 18332097
Cites Am J Ophthalmol. 2008 Dec;146(6):954-9.e1 18760764
Cites N Engl J Med. 2008 Dec 25;359(26):2767-77 19073967
Cites Dev Biol. 2009 May 15;329(2):269-79 19272373
Cites Ann Intern Med. 2009 Sep 15;151(6):404-13 19755365
Cites Eur J Epidemiol. 2009;24(9):553-72 19728115
Cites Twin Res Hum Genet. 2009 Oct;12(5):441-54 19803772
Cites Nature. 2009 Oct 8;461(7265):747-53 19812666
Cites Nat Genet. 2009 Nov;41(11):1182-90 19820697
Cites Nat Genet. 2009 Nov;41(11):1191-8 19862010
Cites Am J Epidemiol. 2009 Dec 1;170(11):1323-32 19884126
Cites Circ Cardiovasc Genet. 2009 Feb;2(1):73-80 20031568
Cites Nat Genet. 2010 Jul;42(7):579-89 20581827
Cites Nat Genet. 2009 Jun;41(6):677-87 19430479
ErratumIn PLoS Genet. 2010;6(11). doi: 10.1371/annotation/841bfadf-85d1-4059-894f-2863d73fa963 19430479 Xueling, Sim [corrected to Sim, Xueling]
GRANTS
GRANTID AGENCY COUNTRY
DK063491 NIDDK NIH HHS United States
G0401527 Medical Research Council United Kingdom
G0701863 Medical Research Council United Kingdom
G0801056 Medical Research Council United Kingdom
M01RR00069 NCRR NIH HHS United States
MC_U105630924 Medical Research Council United Kingdom
MC_UP_A100_1003 Medical Research Council United Kingdom
N01 HC-15103 NHLBI NIH HHS United States
N01-AG-12100 NIA NIH HHS United States
N01-HC-35129 NHLBI NIH HHS United States
N01-HC-45133 NHLBI NIH HHS United States
N01-HC-55015 NHLBI NIH HHS United States
N01-HC-55016 NHLBI NIH HHS United States
N01-HC-55018 NHLBI NIH HHS United States
N01-HC-55019 NHLBI NIH HHS United States
N01-HC-55020 NHLBI NIH HHS United States
N01-HC-55021 NHLBI NIH HHS United States
N01-HC-55022 NHLBI NIH HHS United States
N01-HC-75150 NHLBI NIH HHS United States
N01-HC-85079 NHLBI NIH HHS United States
N01-HC-85086 NHLBI NIH HHS United States
N01HC-55222 NHLBI NIH HHS United States
R01 EY018246 NEI NIH HHS United States
R01 HL087652 NHLBI NIH HHS United States
R01HL087641 NHLBI NIH HHS United States
T32HL007902 NHLBI NIH HHS United States
U01 HL080295 NHLBI NIH HHS United States
U01HG004402 NHGRI NIH HHS United States
UL1RR025005 NCRR NIH HHS United States
Z01 EY000401-06 Intramural NIH HHS United States
Z01 EY000401-07 Intramural NIH HHS United States
Z01 EY000426-04 Intramural NIH HHS United States
Z01 EY000426-05 Intramural NIH HHS United States
Z01AG007380 NIA NIH HHS United States
Z01EY000401 NEI NIH HHS United States
Z01EY000426 NEI 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 EY000403-09 Intramural NIH HHS United States
ZIA EY000403-10 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
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adolescent
Adult
Aged
Aged, 80 and over
Cardiovascular Diseases physiopathology
Child physiopathology
Child, Preschool physiopathology
Chromosomes, Human, Pair 12 physiopathology
Chromosomes, Human, Pair 19 physiopathology
Chromosomes, Human, Pair 5 physiopathology
Chromosomes, Human, Pair 6 physiopathology
Cohort Studies physiopathology
European Continental Ancestry Group genetics
Female genetics
Genetic Loci genetics
Genome-Wide Association Study methods
Humans methods
Male methods
Meta-Analysis as Topic methods
Microcirculation methods
Middle Aged methods
Polymorphism, Single Nucleotide methods
Retinal Vessels physiopathology
Young Adult physiopathology
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's
OTHERID SOURCE
PMC2965750 NLM