Genetic Loci for Retinal Arteriolar Microcirculation

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. UitterlindenCornelia 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, P Donnelly, I Barroso, JM Blackwell, E Bramon, MA Brown, JP Casas, A Corvin, P Deloukas, A Duncanson, J Jankowski, HS Markus, CG Mathew, CN Palmer, R Plomin, A Rautanen, SJ Sawcer, RC Trembath, AC Viswanathan, NW Wood, CC Spencer, G Band, C Bellenguez, C Freeman, G Hellenthal, E Giannoulatou, M Pirinen, R Pearson, A Strange, Z Su, D Vukcevic, P Donnelly, C Langford, SE Hunt, S Edkins, R Gwilliam, H Blackburn, SJ Bumpstead, S Dronov, M Gillman, E Gray, N Hammond, A Jayakumar, OT McCann, J Liddle, SC Potter, R Ravindrarajah, M Ricketts, M Waller, P Weston, S Widaa, P Whittaker, I Barroso, P Deloukas, C Mathew, JM Blackwell, MA Brown, A Corvin, MI McCarthy, CC Spencer, Cheh C Newton, T Johnson, V Gateva, MD Tobin, M Bochud, L Coin, SS Najjar, JH Zhao, SC Heath, S Eyheramendy, K Papadakis, BF Voight, LJ Scott, F Zhang, M Farrall, T Tanaka, C Wallace, JC Chambers, KT Khaw, P Nilsson, der Harst P van, Silvia POLIDORO, DE Grobbee, Moret NC Onland, ML Bots, LV Wain, KS Elliott, A Teumer, J Luan, G Lucas, J Kuusisto, PR Burton, D Hadley, WL McArdle, M Brown, A Dominiczak, SJ Newhouse, NJ Samani, J Webster, E Zeggini, JS Beckmann, S Bergmann, N Lim, K Song, P Vollenweider, G Waeber, DM Waterworth, X Yuan, L Groop, Melander M Orho, A Allione, Gregorio A Di, GUARRERA Simonetta, S Panico, FULVIO RICCERI, V Romanazzi, Carlotta SACERDOTE, VINEIS Paolo, I Barroso, MS Sandhu, RN Luben, GJ Crawford, P Jousilahti, M Perola, M Boehnke, LL Bonnycastle, FS Collins, AU Jackson, KL Mohlke, HM Stringham, TT Valle, CJ Willer, RN Bergman, MA Morken, A Döring, C Gieger, T Illig, T Meitinger, E Org, A Pfeufer, HE Wichmann, S Kathiresan, J Marrugat, CJ O'Donnell, SM Schwartz, DS Siscovick, I Subirana, NB Freimer, AL Hartikainen, MI McCarthy, PF O'Reilly, L Peltonen, A Pouta, Jong PE de, H Snieder, Gilst WH van, R Clarke, A Goel, A Hamsten, JF Peden, U Seedorf, AC Syvänen, G Tognoni, EG Lakatta, S Sanna, P Scheet, D Schlessinger, A Scuteri, M Dörr, F Ernst, SB Felix, G Homuth, R Lorbeer, T Reffelmann, R Rettig, U Völker, P Galan, IG Gut, S Hercberg, GM Lathrop, D Zeleneka, P Deloukas, N Soranzo, FM Williams, G Zhai, V Salomaa, M Laakso, R Elosua, NG Forouhi, H Völzke, CS Uiterwaal, der Schouw YT van, ME Numans, MATULLO Giuseppe, G Navis, G Berglund, SA Bingham, JS Kooner, JM Connell, S Bandinelli, L Ferrucci, H Watkins, TD Spector, J Tuomilehto, D Altshuler, DP Strachan, M Laan, P Meneton, NJ Wareham, M Uda, MR Jarvelin, V Mooser, O Melander, RJ Loos, P Elliott, GR Abecasis, M Caulfield, P.B. Munroe

Risultato della ricerca: Contributo su rivistaArticolo in rivistapeer review

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.
Lingua originaleInglese
pagine (da-a)e65804-e65804
Numero di pagine12
RivistaPLoS ONE
Volume8
Numero di pubblicazione6
DOI
Stato di pubblicazionePubblicato - 2013

Keywords

  • genome-wide association
  • Microcirculation
  • Retinal Arteriolar Microcirculation

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