|
|
| PMID |
|
|
| 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. |
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| DATE PUBLISHED |
|
|
| 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 |
|
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| 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 |
|
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| Wiggins KL |
|
Wiggins |
Kerri L |
KL |
|
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| Heckbert SR |
|
Heckbert |
Susan R |
SR |
|
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| Hammond CJ |
|
Hammond |
Christopher J |
CJ |
|
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| Andrew T |
|
Andrew |
Toby |
T |
|
|
| Fahy S |
|
Fahy |
Samantha |
S |
|
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| Attia J |
|
Attia |
John |
J |
|
|
| Holliday EG |
|
Holliday |
Elizabeth G |
EG |
|
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| Scott RJ |
|
Scott |
Rodney J |
RJ |
|
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| 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 |
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| ErratumIn |
PLoS Genet. 2010;6(11). doi: 10.1371/annotation/841bfadf-85d1-4059-894f-2863d73fa963 |
19430479 |
Xueling, Sim [corrected to Sim, Xueling] |
|
| GRANTS |
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| GRANTID |
AGENCY |
COUNTRY |
| DK063491 |
NIDDK NIH HHS |
United States |
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Medical Research Council |
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Medical Research Council |
United Kingdom |
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Medical Research Council |
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NCRR NIH HHS |
United States |
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Medical Research Council |
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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 |
|
|
