Cancers, Vol. 16, Pages 1578: Breast Cancer Polygenic Risk Score Validation and Effects of Variable Imputation

Cancers, Vol. 16, Pages 1578: Breast Cancer Polygenic Risk Score Validation and Effects of Variable Imputation Cancers doi: 10.3390/cancers16081578 Authors: Jeffrey J. Beck John L. Slunecka Brandon N. Johnson Austin J. Van Asselt Casey T. Finnicum Cheryl Ageton Amy Krie Heidi Nickles Kenneth Cowan Jessica Maxwell Dorret I. Boomsma Eco de Geus Erik A. Ehli Jouke-Jan Hottenga Breast cancer (BC) is a complex disease affecting one in eight women in the USA. Advances in population genomics have led to the development of polygenic risk scores (PRSs) with the potential to augment current risk models, but replication is often limited. We evaluated 2 robust PRSs with 313 and 3820 SNPs and the effects of multiple genotype imputation replications in BC cases and control populations. Biological samples from BC cases and cancer-free controls were drawn from three European ancestry cohorts. Genotyping on the Illumina Global Screening Array was followed by stringent quality control measures and 20 genotype imputation replications. A total of 468 unrelated cases and 4337 controls were scored, revealing significant differences in mean PRS percentiles between cases and controls (p < 0.001) for both SNP sets (313-SNP PRS: 52.81 and 48.07; 3820-SNP PRS: 55.45 and 49.81), with receiver operating characteristic curve analysis showing area under the curve values of 0.596 and 0.603 for the 313-SNP and 3820-SNP PRS, respectively. PRS fluctuations (from ~2&...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research