Risk of developing metabolic and/or cardiovascular disease is partially explained by variation in heritable gene expression. Identifying the loci that control gene expression levels (eQTLs) will allow prioritization of functionally relevant variants in gene mapping studies of disease risk.
We generated genome-wide transcript profiles of blood lymphocytes in 335 individuals forming a large pedigree from the Norfolk Island (NI) isolate. Pedigree-based heritability analysis was used to identify significantly heritable transcripts in NI. GWAS analysis will then be conducted on this subset of transcripts to identify eQTLs in this pedigree.
Results to date have revealed 23326 transcripts (49%) with significant expression levels. Of these 1712 show statistically significant heritability at 5% FDR. The H2 values ranged from 0.18 to 0.83 with a median H2 of 0.32. Preliminary GWAS of highly heritable transcripts has revealed the presence of both cis and trans acting eQTLs (P<1.84*10-7).
So far this study has shown that the Norfolk Island pedigree has identified a panel of heritable transcripts and some large effect eQTLs. Interestingly one major trans-acting eQTL on chr 12 appears to be influencing the expression of multiple different transcripts located on other chromosomes. We will present the final eQTL map as well as results showing association of eQTLs to several metabolic and cardiovascular disease risk traits.