PMC:6323553 / 22134-24143
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{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/6323553","sourcedb":"PMC","sourceid":"6323553","source_url":"https://www.ncbi.nlm.nih.gov/pmc/6323553","text":"Goodness of Fit of the PRS\nThe remaining analyses concentrated on PRS313. The associations between the PRS and breast cancer risk by percentiles of the risk score were compared with those predicted under a simple polygenic model with the PRS considered as a continuous covariate. The effect sizes did not differ from those predicted, and in particular the estimates for the highest and lowest centile were consistent with the predicted estimates (Table S9). Further tests for goodness of fit and tail-based tests (see Material and Methods) were not statistically significant at p \u003c 0.05.\nThere was no evidence of heterogeneity in the effect sizes among studies (Figure 2). All studies showed a significant association with similar effect sizes for overall and ER-positive breast cancer, and all but one study (FHRISK, based on only six case subjects) showed a significant effect for ER-negative breast cancer.\nFigure 2 Prospective Validation for the 313 SNP Polygenic Risk Score\nProspective validation for the 313 SNP polygenic risk score (PRS) by study for (A) overall breast cancer, (B) ER-positive disease, and (C) ER-negative disease. Association between the 313 SNP PRS and breast cancer risk in women of European origin. Odds ratios and 95% confidence intervals are shown. I-squared and p value for heterogeneity were calculated using fixed effect meta-analysis.\nIn the UK Biobank, the estimated hazard ratio (HR) for overall breast cancer per unit PRS (including 306 of the 313 SNPs) was HR = 1.59 (95%CI: 1.54–1.64) (Figure 2).\nBy way of comparison, we also evaluated a PRS based on 177 previously published susceptibility loci.1, 2 The effect size for this PRS (OR = 1.61, 95%CI: 1.57–1.65) in the ten prospective studies was similar to the PRS313. However, this estimated effect size is biased because the validation and test datasets used here contributed to the GWAS discovery datasets; in the UK Biobank this PRS (based on 174 of 177 available SNPs) performed worse (HR = 1.53, 95%CI: 1.48–1.58).","divisions":[{"label":"title","span":{"begin":0,"end":26}},{"label":"p","span":{"begin":27,"end":587}},{"label":"p","span":{"begin":588,"end":1368}},{"label":"figure","span":{"begin":910,"end":1368}},{"label":"label","span":{"begin":910,"end":918}},{"label":"caption","span":{"begin":919,"end":1368}},{"label":"p","span":{"begin":919,"end":978}},{"label":"p","span":{"begin":979,"end":1368}},{"label":"p","span":{"begin":1369,"end":1535}}],"tracks":[{"project":"2_test","denotations":[{"id":"30554720-29059683-2052415","span":{"begin":1636,"end":1637},"obj":"29059683"},{"id":"30554720-29058716-2052416","span":{"begin":1639,"end":1640},"obj":"29058716"}],"attributes":[{"subj":"30554720-29059683-2052415","pred":"source","obj":"2_test"},{"subj":"30554720-29058716-2052416","pred":"source","obj":"2_test"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"2_test","color":"#dc93ec","default":true}]}]}}