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Fine mapping at the TERT locus

Zsofia Kote-Jarai and colleagues report fine mapping of associations to prostate cancer susceptibility at the TERT locus using high-resolution genotyping and imputation (Hum. Mol. Genet. doi:10.1093/hmg/ddt086, 27 March 2013). The authors genotyped 134 SNPs across the TERT locus using the custom iCOGS array or Sequenom MassArray iPlex in 22,301 cases and 22,320 matched controls from 23 studies included in the PRACTICAL Consortium. They initially genotyped 114 SNPs across 135 kb of the SLC6A18-TERT-CLPTM1L region and then narrowed their focus to a 20-kb interval that included variants with stronger association. They further tested association for an imputed set of 1,094 SNPs. They identified 44 SNPs associated with prostate cancer risk at P < 1 × 10−5. With stepwise logistic regression, they were able to identify four SNPs showing independent association, suggesting four separate regions influencing susceptibility to prostate cancer. They examined gene expression of TERT and CLPTM1L in 195 normal (histologically benign) prostate tissue samples isolated from men with elevated prostate-specific antigen (PSA) levels. They found protective alleles of four SNPs in one region associated with higher expression of TERT.


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Bahcall, O. Fine mapping at the TERT locus. Nat Genet 45, 352 (2013).

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