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Int J Mol Epidemiol Genet 2013;4(4):193-206

Original Article
Fine mapping of variants associated with endometriosis in the WNT4 region on
chromosome 1p36

Hien TT Luong, Jodie N Painter, Konstantin Shakhbazov, Brett Chapman, Anjali K Henders, Joseph E Powell, Dale R Nyholt,
Grant W Montgomery

Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland,
Australia; University of Queensland Diamantina Institute, University of Queensland, Princess Alexandra Hospital, Brisbane,
Queensland, Australia

Received September 6, 2013; Accepted October 15, 2013; Epub November 28, 2013; Published December 15, 2013

Abstract: Genome-wide association studies show strong evidence of association with endometriosis for markers on
chromosome 1p36 spanning the potential candidate genes WNT4, CDC42 and LINC00339. WNT4 is involved in development
of the uterus, and the expression of CDC42 and LINC00339 are altered in women with endometriosis. We conducted fine
mapping to examine the role of coding variants in WNT4 and CDC42 and determine the key SNPs with strongest evidence of
association in this region. We identified rare coding variants in WNT4 and CDC42 present only in endometriosis cases. The
frequencies were low and cannot account for the common signal associated with increased risk of endometriosis. Genotypes
for five common SNPs in the region of chromosome 1p36 show stronger association signals when compared with rs7521902
reported in published genome scans. Of these, three SNPs rs12404660, rs3820282, and rs55938609 were located in DNA
sequences with potential functional roles including overlap with transcription factor binding sites for FOXA1, FOXA2, ESR1, and
ESR2. Functional studies will be required to identify the gene or genes implicated in endometriosis risk. (IJMEG1309001).

Keywords: Endometriosis, WNT4, CDC42, chromosome 1p36, rare variants, common variants

Address correspondence to: Dr. Grant W Montgomery, Department of Genetics and Computational Biology, QIMR Berghofer
Medical Research Institute, Brisbane, Queensland, Australia. E-mail: Grant.Montgomery@qimrberghofer.edu.au