Oral Presentation 9th GeneMappers Conference 2012

Heritability and GWAS analysis of ocular phenotypes in the Norfolk Island genetic isolate (#15)

David Eccles 1 , Rod Lea 1 , Justin Sherwin 2 , Alex Hewitt 2 , Miles Benton 1 , Elizabeth Matovinovic 1 , Hannah Cox 1 , Matthew Johnson 3 , Claire Bellis 3 , Melanie Carless 3 , Harald Goring 3 , Joanne Curran 3 , John Blangero 3 , David Mackey 2 , Lyn Griffiths 1
  1. Genomics Research Centre, Griffith Health Institute, Gold Coast, Queensland, Australia
  2. Centre for Eye Research, Melbourne, Australia
  3. Genetics, Texas Biomedical Research Institute, San Antonio, Texas, United States

Glaucoma and myopia are complex eye disorders affecting a large proportion of the population.  The genetic determinants of these conditions and their underlying endophenotypes are only partially known. The large pedigree structure, founder effect and admixture of the Norfolk Island isolate may offer some advantages for studying the genetics of ocular phenotypes.

In this study we statistically analysed 25 ocular phenotypes measured in 801 individuals from the Norfolk Island isolate.  We first performed principal components analysis (PCA) to account for intercorrelation among phenotypes.  Focusing in on the founder pedigree (n=362), we then performed heritability screening of all univariate and multivariate traits to estimate H2, which was followed by pedigree-based GWAS to search for major susceptibility loci.

For the individual ocular phenotypes significant H2 values ranged from 0.20 to 0.78, with the highest H2 obtained for central corneal thickness. The PCA revealed 9 factors that explained 82% of the total variance, with the top 4 factors being significantly heritable (H2min=0.58, P<0.05). Pedigree-based GWAS of all heritable traits revealed multiple SNPs that exceeded the empirical genome-wide significance threshold (P<1.84*10-7).

The results of this analysis highlight some potentially important loci underlying some of these ocular phenotypes. Meta-analysis with other studies and sequencing of members of the Norfolk Island Isolate will clarify some of the genes associated with these ocular measurements.