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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)


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.

Original languageEnglish
Article numbere65804
JournalPLoS ONE
Issue number6
Publication statusPublished - 12 Jun 2013

Bibliographical note

Funding Information:
The authors thank the staff and participants of all the individual studies for their important contributions. We acknowledge funding support by NHBLI grants R01 HL085251 and R01 HL073410 for the Heart and Vascular Health Study. We thank Dr. Michael Moorhouse, Pascal Arp and Mila Jhamai for their help in creating the Rotterdam Study database. David Mackey is a recipient of the Pfizer Australia Senior Research Fellowship. Stuart MacGregor is supported by an Australian NHMRC Career Development Award. We thank Chris Hammond for his design of the Twins Eye Study, Scott Gordon, Anjali Henders, Sarah E Medland, Bryan McEvoy, Dale R. Nyholt, Margaret J. Wright, Megan J. Campbell and Anthony Caracella for their assistance in processing the Australian genotyping data. We are also grateful to Jamie Craig, Jane MacKinnon, Shayne Brown, Lisa Kearns, Sandra Staffieri, Olivia Bigault, Colleen Wilkinson and Julie Barbour who assisted with clinical examinations. Michael Inouye was supported by an NHMRC Biomedical Australian Training Fellowship (no. 637400). We acknowledge the support of the Health Informatics Centre, University of Dundee for managing and supplying the aonymized clinical data for Go-DARTS and NHS Tayside as the original data source. This study makes use of data generated by the Wellcome Trust Case Control Consortium. A full list of the investigators who contributed to the generation of the data is available from . In addition, we would also like to acknowledge Laura Scott and Goncalo Abecasis from the University of Michigan who assisted with the imputation of the HAPMAP SNP data for the WTCCC dataset.

Other keywords

  • Augnsjúkdómar
  • Arfgengi
  • Aldraðir
  • Aged
  • Aged, 80 and over
  • Arterioles
  • Chromosomes, Human, Pair 5
  • European Continental Ancestry Group
  • Female
  • Genetic Loci
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • MEF2 Transcription Factors
  • Male
  • Microcirculation
  • Middle Aged
  • Models, Genetic
  • Retinal Vessels


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