Table 4.
Potential solutions for improving polygenic risk score (PRS) genotyping performance with respect to the achievement of allele frequencies (AFs) expected by CanRisk, using alternative alleles or proxies.
| rs ID | Locus (hg19) | Expected AF | Workaround | gnomAD AF | IMGAG FB AF |
|---|---|---|---|---|---|
| rs12406858 | 1-118141492-A-C | 0.2654 | Proxy rs1966228 | 0.2622 | 0.3064 |
| rs11693806 | 2-218292158-C-G | 0.7289 | Proxy rs3821098 | 0.7422 | 0.7443 |
| rs34207738 | 3-141112859-CTT-C | 0.4205 | Summing up the AFs of deletions of two and three thymines | 0.4344 | 0.4167 |
| rs10074269 | 5-169591460-T-C | 0.3393 | Proxy rs4562056 | 0.3414 | 0.3511 |
| rs73754909 | 6-87803819-T-C | 0.2809 | Alternative allele rs77846138a | 0.2846 | 0.2578 |
| Proxy rs12664322 | 0.2849 | 0.2791 | |||
| rs55941023 | 6-130341728-C-CT | 0.7113 | Proxy rs1415700 | 0.7049 | 0.7050 |
| Proxy rs11390217 | 0.7058 | 0.7046 | |||
| rs1511243 | 8-76230943-A-G | 0.8289 | Proxy rs6472903 | 0.8294 | 0.8376 |
| rs10975870 | 9-6880263-A-G | 0.2900 | Proxy rs12380608 | 0.2863 | 0.2840 |
| Proxy rs10975887 | 0.2849 | 0.2837 | |||
| rs4880038 | 9-36928288-T-C | 0.5427 | Proxy rs4880039 | 0.5449 | 0.5436 |
| Proxy rs7032313 | 0.5446 | 0.5440 | |||
| rs542275778 | 10-22477776-ACC-A | 0.0214 | Proxy rs112287594 | 0.0185 | 0.0270 |
| rs111833376 | 10-71335574-C-T | 0.3122 | Summing up AFs of rs111833376 and rs753981427b | 0.3200 | 0.3163 |
| Proxy rs12769661 | 0.2984 | 0.2929 | |||
| rs9421410 | 10-123095209-G-A | 0.3246 | Proxy rs7913694 | 0.3142 | 0.3110 |
| Proxy rs35098964 | 0.3139 | 0.3099 | |||
| rs35054928 | 10-123340431-GC-G | 0.5971 | Proxy rs2981579 | 0.5908 | 0.5996 |
| rs11049431 | 12-28347382-C-T | 0.2151 | Proxy rs11049519 | 0.2142 | 0.2039 |
| rs144767203 | 15-100905819-A-C | 0.1072 | Proxy rs58855876 | 0.1078 | 0.1043 |
| Proxy rs113438754 | 0.1078 | 0.1043 | |||
| rs12709163 | 16-6963972-C-G | 0.7915 | Proxy rs1492386 | 0.7951 | 0.7684 |
| rs9931038 | 16-85145977-T-C | 0.4851 | Proxy rs60296580 | 0.4903 | 0.5082 |
| rs79461387 | 17-29168077-G-T | 0.2573 | Alternative allele rs550458309c | 0.2719 | 0.0000 |
| rs2668667 | 17-44283858-G-A | 0.1919 | Proxy rs2532237 | 0.1860 | 0.1957 |
| Proxy rs150290194 | 0.1765 | 0.1858 | |||
| rs1111207 | 18-24125857-T-C | 0.4243 | Proxy rs1111208 | 0.4249 | 0.4135 |
| rs66987842 | 22-40904707-CT-C | 0.1068 | Proxy rs6001949 | 0.1003 | 0.1195 |
Resulting AFs were investigated based on gnomAD v3.1.2 non-Finnish European data and genotyping results of 1410 European whole-genome sequencing (WGS) samples using (unforced) freebayes (FB), provided by the Institute of Medical Genetics and Applied Genomics (IMGAG) at University Hospital Tübingen.
a6-87094100-CAGAAACTTTAAAAGATTCCTTTT-C (hg19).
b10-71335572-TCC-T (hg19).
c17-29168076-AGAG-A (hg19).