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

Publication ,  Journal Article
Ikram, MK; Sim, X; Jensen, RA; Cotch, MF; Hewitt, AW; Ikram, MA; Wang, JJ; Klein, R; Klein, BEK; Breteler, MMB; Cheung, N; Liew, G; Hofman, A ...
Published in: PLoS Genet
October 28, 2010

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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Published In

PLoS Genet

DOI

EISSN

1553-7404

Publication Date

October 28, 2010

Volume

6

Issue

10

Start / End Page

e1001184

Location

United States

Related Subject Headings

  • Young Adult
  • White People
  • Retinal Vessels
  • Polymorphism, Single Nucleotide
  • Middle Aged
  • Microcirculation
  • Meta-Analysis as Topic
  • Male
  • Humans
  • Genome-Wide Association Study
 

Citation

APA
Chicago
ICMJE
MLA
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Ikram, M. K., Sim, X., Jensen, R. A., Cotch, M. F., Hewitt, A. W., Ikram, M. A., … Wong, T. Y. (2010). Four novel Loci (19q13, 6q24, 12q24, and 5q14) influence the microcirculation in vivo. PLoS Genet, 6(10), e1001184. https://doi.org/10.1371/journal.pgen.1001184
Ikram, M Kamran, Xueling Sim, Richard A. Jensen, Mary Frances Cotch, Alex W. Hewitt, M Arfan Ikram, Jie Jin Wang, et al. “Four novel Loci (19q13, 6q24, 12q24, and 5q14) influence the microcirculation in vivo.PLoS Genet 6, no. 10 (October 28, 2010): e1001184. https://doi.org/10.1371/journal.pgen.1001184.
Ikram MK, Sim X, Jensen RA, Cotch MF, Hewitt AW, Ikram MA, et al. Four novel Loci (19q13, 6q24, 12q24, and 5q14) influence the microcirculation in vivo. PLoS Genet. 2010 Oct 28;6(10):e1001184.
Ikram, M. Kamran, et al. “Four novel Loci (19q13, 6q24, 12q24, and 5q14) influence the microcirculation in vivo.PLoS Genet, vol. 6, no. 10, Oct. 2010, p. e1001184. Pubmed, doi:10.1371/journal.pgen.1001184.
Ikram MK, Sim X, Jensen RA, Cotch MF, Hewitt AW, Ikram MA, Wang JJ, Klein R, Klein BEK, Breteler MMB, Cheung N, Liew G, Mitchell P, Uitterlinden AG, Rivadeneira F, Hofman A, de Jong PTVM, van Duijn CM, Kao L, Cheng C-Y, Smith AV, Glazer NL, Lumley T, McKnight B, Psaty BM, Jonasson F, Eiriksdottir G, Aspelund T, Global BPgen Consortium, Harris TB, Launer LJ, Taylor KD, Li X, Iyengar SK, Xi Q, Sivakumaran TA, Mackey DA, Macgregor S, Martin NG, Young TL, Bis JC, Wiggins KL, Heckbert SR, Hammond CJ, Andrew T, Fahy S, Attia J, Holliday EG, Scott RJ, Islam FMA, Rotter JI, McAuley AK, Boerwinkle E, Tai ES, Gudnason V, Siscovick DS, Vingerling JR, Wong TY. Four novel Loci (19q13, 6q24, 12q24, and 5q14) influence the microcirculation in vivo. PLoS Genet. 2010 Oct 28;6(10):e1001184.

Published In

PLoS Genet

DOI

EISSN

1553-7404

Publication Date

October 28, 2010

Volume

6

Issue

10

Start / End Page

e1001184

Location

United States

Related Subject Headings

  • Young Adult
  • White People
  • Retinal Vessels
  • Polymorphism, Single Nucleotide
  • Middle Aged
  • Microcirculation
  • Meta-Analysis as Topic
  • Male
  • Humans
  • Genome-Wide Association Study