Four novel Loci (19q13, 6q24, 12q24, and 5q14) influence the microcirculation in vivo.


Serval ID
Article: article from journal or magazin.
Four novel Loci (19q13, 6q24, 12q24, and 5q14) influence the microcirculation in vivo.
Plos Genetics
Ikram M.K., Sim X., Xueling S., Jensen R.A., Cotch M.F., Hewitt A.W., Ikram M.A., Wang J.J., Klein R., Klein B.E., Breteler M.M., Cheung N., Liew G., Mitchell P., Uitterlinden A.G., Rivadeneira F., Hofman A., de Jong P.T., van Duijn C.M., Kao L., Cheng C.Y., Smith A.V., Glazer N.L., Lumley T., McKnight B., Psaty B.M., Jonasson F., Eiriksdottir G., Aspelund T., Harris T.B., Harris T.B., Launer L.J., Taylor K.D., Li X., Iyengar S.K., Xi Q., Sivakumaran T.A., Mackey D.A., Macgregor S., Martin N.G., Young T.L., Bis J.C., Wiggins K.L., Heckbert S.R., Hammond C.J., Andrew T., Fahy S., Attia J., Holliday E.G., Scott R.J., Islam F.M., Rotter J.I., McAuley A.K., Boerwinkle E., Tai E.S., Gudnason V., Siscovick D.S., Vingerling J.R., Wong T.Y.
Working group(s)
Global BPgen Consortium
Newton-Cheh C., Johnson T., Gateva V., Tobin MD., Bochud M., Coin L., Najjar SS., Zhao JH., Heath SC., Eyheramendy S., Papadakis K., Voight BF., Scott LJ., Zhang F., Farrall M., Tanaka T., Wallace C., Chambers JC., Khaw KT., Nilsson P., van der Harst P., Polidoro S., Grobbee DE., Onland-Moret NC., Bots ML., Wain LV., Elliott KS., Teumer A., Luan£££Jian'an£££ J. , Lucas G., Kuusisto J., Burton PR., Hadley D., McArdle WL., Brown M., Dominiczak A., Newhouse SJ., Samani NJ., Webster J., Zeggini E., Beckmann JS., Bergmann S., Lim N., Song K., Vollenweider P., Waeber G., Waterworth DM., Yuan X., Groop L., Orho-Melander M., Allione A., Di Gregorio A., Guarrera S., Panico S., Ricceri F., Romanazzi V., Sacerdote C., Vineis P., Barroso£££Inîs£££ I. , Sandhu MS., Luben RN., Crawford GJ., Jousilahti P., Perola M., Boehnke M., Bonnycastle LL., Collins FS., Jackson AU., Mohlke KL., Stringham HM., Valle TT., Willer CJ., Bergman RN., Morken MA., Döring A., Gieger C., Illig T., Meitinger T., Org E., Pfeufer A., Wichmann HE., Kathiresan S., Marrugat J., O'Donnell CJ., Schwartz SM., Siscovick DS., Subirana I., Freimer NB., Hartikainen AL., McCarthy MI., O'Reilly PF., Peltonen L., Pouta A., de Jong PE. , Snieder H., van Gilst WH. , Clarke R., Goel A., Hamsten A., Peden JF., Seedorf U., Syvänen AC., Tognoni G., Lakatta EG., Sanna S., Scheet P., Schlessinger D., Scuteri A., Dörr M., Ernst F., Felix SB., Homuth G., Lorbeer R., Reffelmann T., Rettig R., Völker U., Galan P., Gut IG., Hercberg S., Lathrop GM., Zeleneka D., Deloukas P., Soranzo N., Williams FM., Zhai G., Salomaa V., Laakso M., Elosua R., Forouhi NG., Völzke H., Uiterwaal CS., van der Schouw YT. , Numans ME., Matullo G., Navis G., Berglund G., Bingham SA., Kooner JS., Connell JM., Bandinelli S., Ferrucci L., Watkins H., Spector TD., Tuomilehto J., Altshuler D., Strachan DP., Laan M., Meneton P., Wareham NJ., Uda M., Jarvelin MR., Mooser V., Melander O., Loos RJ., Elliott P., Abecasis GR., Caulfield M., Munroe PB.
1553-7404 (Electronic)
Publication state
Issued date
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: epublish
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.
Adolescent, Adult, Aged, Aged, 80 and over, Cardiovascular Diseases/genetics, Cardiovascular Diseases/physiopathology, Child, Child, Preschool, Chromosomes, Human, Pair 12, Chromosomes, Human, Pair 19, Chromosomes, Human, Pair 5, Chromosomes, Human, Pair 6, Cohort Studies, European Continental Ancestry Group/genetics, Female, Genetic Loci/genetics, Genome-Wide Association Study/methods, Humans, Male, Meta-Analysis as Topic, Microcirculation, Middle Aged, Polymorphism, Single Nucleotide, Retinal Vessels/physiopathology, Young Adult
Web of science
Open Access
Create date
01/12/2010 11:26
Last modification date
20/08/2019 17:10
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