April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Genome-Wide Analysis of Mitochondrial DNA (mtDNA)-Nuclear DNA Interaction in Age-Related Macular Degeneration (AMD)
Author Affiliations & Notes
  • Patrice Persad
    Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL
  • Monique Dorcel Courtenay
    Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL
  • Gaofeng Wang
    Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL
  • William Cade
    Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL
  • Anita Agarwal
    Vanderbilt University, Nashville, TN
  • Stephen G Schwartz
    Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL
  • Jaclyn L Kovach
    Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL
  • Jonathan L Haines
    Institute of Computational Biology, Case Western Reserve University, Cleveland, OH
  • Margaret A Pericak-Vance
    Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL
  • William K Scott
    Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL
  • Footnotes
    Commercial Relationships Patrice Persad, None; Monique Courtenay, None; Gaofeng Wang, None; William Cade, None; Anita Agarwal, None; Stephen Schwartz, Alimera (C), Bausch + Lomb (C), Regeneron (R), Santen (C), ThromboGenics (R); Jaclyn Kovach, None; Jonathan Haines, None; Margaret Pericak-Vance, None; William Scott, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 2220. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Patrice Persad, Monique Dorcel Courtenay, Gaofeng Wang, William Cade, Anita Agarwal, Stephen G Schwartz, Jaclyn L Kovach, Jonathan L Haines, Margaret A Pericak-Vance, William K Scott; Genome-Wide Analysis of Mitochondrial DNA (mtDNA)-Nuclear DNA Interaction in Age-Related Macular Degeneration (AMD). Invest. Ophthalmol. Vis. Sci. 2014;55(13):2220.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose: Reactive oxygen species (ROS) contribute to retinal pigment epithelium (RPE) degeneration and mitochondrial dysfunction, both of which characterize AMD. Prior studies suggested that mtDNA haplogroup H was protective for AMD and was associated with increased CFH and C3 expression (Kenney et al., 2013). We examined joint effects of mtDNA variants and nuclear DNA in a genome-wide analysis.

Methods: An existing genome-wide association study (GWAS) dataset (Naj et al., 2013) of 668,238 single nucleotide polymorphisms (SNPs) from the Affymetrix 6.0 chipset was analyzed. A total of 1,419 people with smoking history were included: 894 cases (CARMS grades 3, 4, and 5) and 525 controls (grades 1 and 2). A two-degree of freedom joint test of gene-gene interaction was conducted using PLINK. In this test, a model including the nuclear SNP (coded additively), the mtDNA SNP (coded 0,1), and the nuclear SNP-mtDNA SNP interaction term was compared to a second model excluding the nuclear SNP and interaction terms. Both models were adjusted for age, sex, and smoking. Interaction was assessed for 26 mtDNA SNPs and all 668,212 nuclear SNPs available.

Results: Joint effects of mtDNA SNP rs3928306 and nuclear DNA variants rs13375236, rs6428369, and rs2336503 in the CFH region achieved genome-wide statistical significance (p<5.00x10-8) with interaction effects being nominally statistically significant (p<0.01). No novel nuclear DNA variants demonstrated genome-wide statistical significance.

Conclusions: The mtDNA variant rs3928306 (which is found on mitochondrial subhaplogroup H1) may be a modifier of the association of variation in the CFH region with AMD. However, further investigation is required to determine the exact biological significance in mechanisms concerning AMD and to confirm consistency in other datasets.

Keywords: 412 age-related macular degeneration • 539 genetics • 464 clinical (human) or epidemiologic studies: risk factor assessment  
×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×