TY - JOUR T1 - A polygenic risk score for breast cancer in U.S. Latinas and Latin-American women JF - bioRxiv DO - 10.1101/598730 SP - 598730 AU - Yiwey Shieh AU - Laura Fejerman AU - Paul C. Lott AU - Katie Marker AU - Sarah D. Sawyer AU - Donglei Hu AU - Scott Huntsman AU - Javier Torres AU - Magdalena Echeverry AU - Mabel E. Bohorquez AU - Juan Carlos Martínez-Chéquer AU - Guadalupe Polanco-Echeverry AU - Ana P. Estrada-Florez AU - the COLUMBUS Consortium AU - Christopher A. Haiman AU - Esther M. John AU - Lawrence H. Kushi AU - Gabriela Torres-Mejía AU - Tatianna Vidaurre AU - Jeffrey N. Weitzel AU - Sandro Casavilca Zambrano AU - Luis G. Carvajal-Carmona AU - Elad Ziv AU - Susan L. Neuhausen Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/07/24/598730.abstract N2 - Background Over 180 single nucleotide polymorphisms (SNPs) associated with breast cancer susceptibility have been identified; these SNPs can be combined into polygenic risk scores (PRS) to predict breast cancer risk. Since most SNPs were identified in predominantly European populations, little is known about the performance of PRS in non-Europeans. We tested the performance of a 180-SNP PRS in Latinas, a large ethnic group with variable levels of Indigenous American, European, and African ancestry.Methods We conducted a pooled case-control analysis of U.S. Latinas and Latin-American women (4,658 cases, 7,622 controls). We constructed a 180-SNP PRS consisting of SNPs associated with breast cancer risk (p < 5 × 10−8). We evaluated the association between the PRS and breast cancer risk using multivariable logistic regression and assessed discrimination using area under the receiver operating characteristic curve (AUROC). We also assessed PRS performance across quartiles of Indigenous American genetic ancestry.Results Of 180 SNPs tested, 142 showed directionally consistent associations compared with European populations, and 39 were nominally significant (p < 0.05). The PRS was associated with breast cancer risk, with an odds ratio (OR) per standard deviation increment of 1.58 (95% CI 1.52 to 1.64) and AUCROC of 0.63 (95% CI 0.62 to 0.64). The discrimination of the PRS was similar between the top and bottom quartiles of Indigenous American ancestry.Conclusions The 180-SNP PRS predicts breast cancer risk in Latinas, with similar performance as reported for Europeans. The performance of the PRS did not vary substantially according to Indigenous American ancestry. ER -