Data di Pubblicazione:
2013
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.
Tipologia CRIS:
03A-Articolo su Rivista
Keywords:
genome-wide association; Microcirculation; Retinal Arteriolar Microcirculation
Elenco autori:
Xueling Sim;Richard A. Jensen;M. Kamran Ikram;Mary Frances Cotch;Xiaohui Li;Stuart MacGregor;Jing Xie;Albert Vernon Smith;Eric Boerwinkle;Paul Mitchell;Ronald Klein;Barbara E. K. Klein;Nicole L. Glazer;Thomas Lumley;Barbara McKnight;Bruce M. Psaty;Paulus T. V. M. de Jong;Albert Hofman;Fernando Rivadeneira;Andre G. Uitterlinden;Cornelia M. van Duijn;Thor Aspelund;Gudny Eiriksdottir;Tamara B. Harris;Fridbert Jonasson;Lenore J. Launer;John Attia;Paul N. Baird;Stephen Harrap;Elizabeth G. Holliday;Michael Inouye;Elena Rochtchina;Rodney J. Scott;Ananth Viswanathan;Guo Li;Nicholas L. Smith;Kerri L. Wiggins;Jane Z. Kuo;Kent D. Taylor;Alex W. Hewitt;Nicholas G. Martin;Grant W. Montgomery;Cong Sun;Terri L. Young;David A. Mackey;Natalie R. van Zuydam;Alex S. F. Doney;Colin N. A. Palmer;Andrew D. Morris;Jerome I. Rotter;E. Shyong Tai;Vilmundur Gudnason;Johannes R. Vingerling;David S. Siscovick;Jie Jin Wang;Tien Y. Wong; Donnelly P; Barroso I; Blackwell JM; Bramon E; Brown MA; Casas JP; Corvin A; Deloukas P; Duncanson A; Jankowski J; Markus HS; Mathew CG; Palmer CN; Plomin R; Rautanen A; Sawcer SJ; Trembath RC; Viswanathan AC; Wood NW; Spencer CC; Band G; Bellenguez C; Freeman C; Hellenthal G; Giannoulatou E; Pirinen M; Pearson R; Strange A; Su Z; Vukcevic D; Donnelly P; Langford C; Hunt SE; Edkins S; Gwilliam R; Blackburn H; Bumpstead SJ; Dronov S; Gillman M; Gray E; Hammond N; Jayakumar A; McCann OT; Liddle J; Potter SC; Ravindrarajah R; Ricketts M; Waller M; Weston P; Widaa S; Whittaker P; Barroso I; Deloukas P; Mathew C; Blackwell JM; Brown MA; Corvin A; McCarthy MI; Spencer CC; 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 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 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.
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