Grant W. Montgomery1, Dale R. Nyholt1, Hien T.T. Luong1, K. Shakhbazov2, D.J. Gerhardt3, A.K. Henders1, A. Caracella1, L. Bowdler1, L. Wallace1, J. Crawford2, J.A. Jeddeloh3, T.R. Mercer2, M. Amir3, M.E. Dinger3, P.A.W. Rogers4
(1) Queensland Institute of Medical Research, Brisbane, Australia (2) University of Queensland, Brisbane, Australia (3) Roche NimbleGen Inc, Research and Development, Madison, U.S.A. (4) University of Melbourne, Melbourne, Australia

Genome-wide association studies provide strong support for genetic factors contributing to endometriosis risk and have identified three regions associated with endometriosis located on chromosomes 1, 7 and 9. An important step in translating these results into an improved understanding of disease mechanisms is to identify the relevant gene or genes in each region contributing to disease risk. We are combining data from international sequencing projects with gene expression and further genetic studies to search for the genes responsible and likely causal variants. We have sequenced pools of RNA from endometrial samples and are conducting RNA capture and sequencing of individual samples to look for novel transcripts, allele specific splice variants and differences in gene expression. Rare coding variants in genes in some high risk families might also point to the likely casual genes. We are sequencing the coding regions of putative candidate genes and have identified a novel coding variant and an insertion/deletion in the 3’UTR in WNT4. These were private variants restricted to the families where they were first identified. Our results also show many common variants contribute to risk and there is evidence for stronger genetic contributions to severe disease. Larger studies will identify additional genes contributing to risk and help to understand pathways affecting disease risk.