PMC:6323553 / 4447-7608 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/6323553","sourcedb":"PMC","sourceid":"6323553","source_url":"https://www.ncbi.nlm.nih.gov/pmc/6323553","text":"Study Subjects and Genotyping\nThe dataset used for development of the PRSs comprised 94,075 breast cancer-affected case subjects and 75,017 control subjects of European ancestry from 69 studies in the BCAC (Tables S1 and S2). Data collection for individual studies is described previously.1 Samples were genotyped using one of two arrays: iCOGS13, 14 and OncoArray.1, 15 The dataset was divided into a training and validation set. The validation set was randomly selected (approximately 10% of case and control subjects) from studies that had been genotyped with the OncoArray, after excluding studies of bilateral breast cancer, studies or sub-studies oversampling for family history, and individuals with in situ cancers or case subjects with unknown ER status.\nThe best PRSs were evaluated in an independent test dataset comprising 11,428 invasive breast cancer-affected case subjects and 18,323 control subjects from ten studies nested within prospective cohorts, all genotyped using the OncoArray (Tables S3 and S4). The overall breast cancer PRS was also evaluated among 190,040 women of European ancestry from the UK Biobank cohort who had not had any cancer diagnosis or mastectomy prior to recruitment. A total of 3,215 incident registry-confirmed invasive breast cancers developed over 1,381,019 person years of prospective follow-up. Follow-up started 6 months after age of baseline questionnaire. The primary endpoint was invasive breast cancer. Follow-up was censored at the earliest of: risk-reducing mastectomy, diagnosis of any type of cancer, death, or January 15, 2017.\nGenotype calling, quality control, and imputation for iCOGS and OncoArray were performed as previously described.1, 14 Briefly, imputation was performed for the iCOGS and OncoArray datasets separately using the Phase 3 (October 2014) release of the 1000 Genomes data as reference.16 We followed a two-stage approach using SHAPEIT for phasing17 and IMPUTE2 for the imputation.15 Where samples were genotyped with iCOGS and OncoArray, the OncoArray calling was used. SNPs with MAF \u003e 0.01 and imputation r2 \u003e 0.9 for OncoArray and r2 \u003e 0.3 for iCOGS were included in this analysis (∼7 million SNPs); a higher threshold was imposed for OncoArray to ensure accurate determination of the PRS in the validation and test datasets.\nUK Biobank samples were genotyped using Affymetrix UK BiLEVE Axiom array and Affymetrix UK Biobank Axiom array and imputed to the combined 1000 Genomes Project v.3 and UK10K reference panels using SHAPEIT3 and IMPUTE3.18 The lowest imputation info score for the SNPs used in these analyses was 0.86. Samples were included on the basis of female sex (genetic and self-reported) and ethnicity filter (Europeans/White British ancestry subset). Duplicates, individuals with high degree of relatedness (\u003e10 relatives), and one of each related pair of first degree relatives were removed. Samples were also excluded using standard quality control criteria.\nParticipants provided written informed consent, all studies were approved by the relevant ethics committees, and procedures followed were in accordance with the ethical standards of these committees.","divisions":[{"label":"title","span":{"begin":0,"end":29}},{"label":"p","span":{"begin":30,"end":763}},{"label":"p","span":{"begin":764,"end":1587}},{"label":"p","span":{"begin":1588,"end":2310}},{"label":"p","span":{"begin":2311,"end":2961}}],"tracks":[{"project":"2_test","denotations":[{"id":"30554720-29059683-2052393","span":{"begin":289,"end":290},"obj":"29059683"},{"id":"30554720-25751625-2052394","span":{"begin":344,"end":346},"obj":"25751625"},{"id":"30554720-23535729-2052395","span":{"begin":348,"end":350},"obj":"23535729"},{"id":"30554720-29059683-2052396","span":{"begin":365,"end":366},"obj":"29059683"},{"id":"30554720-27697780-2052397","span":{"begin":368,"end":370},"obj":"27697780"},{"id":"30554720-29059683-2052398","span":{"begin":1701,"end":1702},"obj":"29059683"},{"id":"30554720-23535729-2052399","span":{"begin":1704,"end":1706},"obj":"23535729"},{"id":"30554720-26432245-2052400","span":{"begin":1868,"end":1870},"obj":"26432245"},{"id":"30554720-24743097-2052401","span":{"begin":1929,"end":1931},"obj":"24743097"},{"id":"30554720-27697780-2052402","span":{"begin":1963,"end":1965},"obj":"27697780"},{"id":"30554720-27270105-2052403","span":{"begin":2529,"end":2531},"obj":"27270105"}],"attributes":[{"subj":"30554720-29059683-2052393","pred":"source","obj":"2_test"},{"subj":"30554720-25751625-2052394","pred":"source","obj":"2_test"},{"subj":"30554720-23535729-2052395","pred":"source","obj":"2_test"},{"subj":"30554720-29059683-2052396","pred":"source","obj":"2_test"},{"subj":"30554720-27697780-2052397","pred":"source","obj":"2_test"},{"subj":"30554720-29059683-2052398","pred":"source","obj":"2_test"},{"subj":"30554720-23535729-2052399","pred":"source","obj":"2_test"},{"subj":"30554720-26432245-2052400","pred":"source","obj":"2_test"},{"subj":"30554720-24743097-2052401","pred":"source","obj":"2_test"},{"subj":"30554720-27697780-2052402","pred":"source","obj":"2_test"},{"subj":"30554720-27270105-2052403","pred":"source","obj":"2_test"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"2_test","color":"#a693ec","default":true}]}]}}