Table 3.
Nominally significant rare-variant tests for breast cancer overall and by estrogen receptor status, across all ethnicities
| Outcome | Gene | Chromosome: index SNP | Number of variants | CP | Significant test(s) | p value | OR (95 % CI) |
|---|---|---|---|---|---|---|---|
| Breast cancer overall | ORAOV1 | Chr11: rs614367 | 43 | 4.80 % | SKAT | 0.004 | 0.8 (0.6–1.1) |
| GTPBP3 | Chr19: rs8170 | 48 | 3.50 % | SKAT | 0.01 | 1.3 (0.9–1.8) | |
| GLT25D1 | Chr19: rs8170 | 55 | 2.50 % | SKAT | 0.015 | 0.9 (0.7–1.4) | |
| DDA1 - p2 | Chr19: rs8170 | 1 | <1.0 % | SKAT | 0.046 | 2.0 (0.9–4.1) | |
| NSMCE4A | Chr10: rs2981579 | 17 | 0.70 % | BURDEN | 0.023 | 0.4 (0.2–0.9) | |
| ANO8 - p2 | Chr19: rs8170 | 8 | <1.7 % | BURDEN | 0.034 | 5.3 (1.1–24.2) | |
| ER+ | GTPBP3 | Chr19: rs8170 | 48 | 3.50 % | SKAT | 0.007 | 1.4 (1.0–2.1) |
| TMEM221 - p2 | Chr19: rs8170 | 5 | <2.1 % | SKAT | 0.013 | 0.4 (0.2–1.0) | |
| GLT25D1 | Chr19: rs8170 | 55 | 2.50 % | SKAT | 0.018 | 0.8 (0.5–1.3) | |
| ZNF365 - p2 | Chr10: rs10995190 | 8 | <2.0 % | SKAT, BURDEN | 0.019 | 2.5 (1.0–5.9) | |
| ORAOV1 | Chr11: rs614367 | 43 | 4.80 % | SKAT | 0.024 | 0.8 (0.6–1.1) | |
| TMEM221 | Chr19: rs8170 | 24 | 2.10 % | SKAT | 0.028 | 0.6 (0.4–1.1) | |
| ZFYVE26 | Chr14: rs999737 | 126 | 5.70 % | SKAT | 0.041 | 1.2 (0.9–1.5) | |
| MAP1S - p2 | Chr19: rs8170 | 22 | <4.9 % | SKAT | 0.045 | 0.9 (0.6–1.5) | |
| GLT25D1 - p2 | Chr19: rs8170 | 15 | <2.5 % | SKAT | 0.049 | 0.9 (0.4–1.9) | |
| ZNF365 | Chr10: rs10995190 | 38 | 2.00 % | BURDEN | 0.013 | 1.8 (1.1–2.9) | |
| PLVAP | Chr19: rs8170 | 31 | 1.80 % | BURDEN | 0.016 | 1.8 (1.1–3.0) | |
| FGFR2 | Chr10: rs2981579 | 41 | 1.50 % | BURDEN | 0.016 | 2.0 (1.1–3.4) | |
| C6orf211 | Chr6: rs2046210 | 34 | 2.70 % | BURDEN | 0.044 | 0.6 (0.4–1.0) | |
| ER− | ORAOV1 | Chr11: rs614367 | 43 | 4.80 % | SKAT | 0.028 | 0.9 (0.5–1.4) |
| ANO8 - p2 | Chr19: rs8170 | 8 | <1.7 % | SKAT | 0.028 | 4.4 (0.3–74.5) | |
| FAM129C | Chr19: rs8170 | 62 | 6.80 % | SKAT | 0.035 | 0.9 (0.6–1.3) | |
| BABAM1 | Chr19: rs8170 | 24 | 1.40 % | SKAT | 0.041 | 2.1 (0.9–5.1) | |
| ORAOV1 - p2 | Chr11: rs614367 | 2 | <4.8 % | SKAT | 0.042 | 3.3E + 06 (0.0– > 1E50) | |
| UNC13A | Chr19: rs8170 | 69 | 3.70 % | SKAT | 0.045 | 1.5 (0.9–2.5) | |
| ZFYVE26 | Chr14: rs999737 | 126 | 5.70 % | SKAT | 0.049 | 1.5 (1.0–2.3) | |
| USE1 | Chr19: rs8170 | 14 | 0.40 % | BURDEN, SKAT | 0.022 | 7.2 (1.3–38.8) | |
| ABHD8 | Chr19: rs8170 | 19 | 1.30 % | BURDEN | 0.026 | 2.4 (1.1–5.0) | |
| TMEM221 | Chr19: rs8170 | 24 | 2.10 % | BURDEN | 0.029 | 2.1 (1.1–3.9) | |
| ZFYVE26 - p2 | Chr14: rs999737 | 29 | <5.7 % | BURDEN | 0.031 | 2.5 (1.1–5.7) |
Abbreviations: SNP Single-nucleotide polymorphism, p2 Subset of variants within gene predicted to be potentially or possibly damaging by Polymorphism Phenotyping version 2, CP Carrier proportion or proportion of subjects who carry at least one rare, nonsynonymous variant in gene, BURDEN Inverse-variance-weighted burden test, SKAT Meta-analysis of sequence kernel association test assuming the effect of each variant is homogeneous, regardless of ethnicity
Underlining = lowest p value if more than one significant test