Table 1. Novel genome-wide significant associations of mCAs with inherited variants.
| GWAS | Risk allelic shift in hets | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
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| ||||||||||
| SV type | Locus | Variant | Location | Allelesa | RAFb | P | OR(95% CI) | Nincc | Ndec | P |
| cis | ||||||||||
| associations | ||||||||||
| 10q loss | FRA10B | rs118137427d | 10q25.2 | A/G | 0.05 | 6.1×10−42 | 18 (12–26) | 0 | 43 | 2.3×10−13 |
| 1p CNN-LOH | MPL | rs144279563 | 1p34.1 | C/T | 0.0005 | 6.2×10−16 | 53 (28–99) | 0 | 9 | 3.9×10−3 |
| rs182971382 | 1p34.1 | A/G | 0.0003 | 3.0×10−11 | 63 (29–139) | 0 | 4 | 1.3×10−1 | ||
| rs369156948e | 1p34.2 | C/T | 0.0001 | 7.3×10−8 | 103 (35–300) | 0 | 3 | 2.5×10−1 | ||
| 11q CNN-LOH | ATM | rs532198118 | 11q22.3 | A/G | 0.0007 | 7.4×10−9 | 41 (18–94) | 6 | 0 | 3.1×10−2 |
| 15q CNN-LOH and loss | TM2D3, TARSL2 | 70kb deletionf | 15q26.3 | CN=1/0 | 0.0003 | 1.3×10−86 | 698 (442–1102) | 39 | 2 | 7.8×10−10 |
| chrX loss | DXZ1 | rs2942875 | Xp11.1 | T/C | 0.55 | 9.7×10−4 | 1.09 (1.04–1.15) | 423 | 796 | 6.6×10−27 |
| DXZ4 | rs11091036 | Xq23 | C/G | 0.73 | 1.1×10−3 | 1.10 (1.04–1.17) | 369 | 555 | 1.0×10−9 | |
|
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| trans | ||||||||||
| associations | ||||||||||
| chrX loss | SP140L | rs725201 | 2q37.1 | G/T | 0.56 | 9.2×10−10 | 1.17 (1.12–1.24) | – | – | – |
| HLA | rs141806003 | 6p21.33 | C/CAAAG | 0.34 | 6.1×10−10 | 1.18 (1.12–1.25) | – | – | – | |
Results of two independent association tests are reported: (i) a Fisher test treating individuals with a given mCA type as cases; and (ii) (for cis associations) a binomial test for biased allelic imbalance in heterozygous cases (Methods). All loci reaching P<1×10−8 in either test are reported; each cis association detected by one test reached nominal (P<0.05) significance in the other test. At significant loci, the lead associated variant as well as additional independent associations reaching P<1×10−6 are reported.
Risk lowering/risk increasing allele.
Risk allele frequency (in UK Biobank European-ancestry individuals).
Number of mosaic individuals heterozygous for the variant in which the somatic event shifted the allelic balance in favor of the risk allele (by duplication of its chromosomal segment and/or loss of the homologous segment).
rs118137427 tags expanded repeats at FRA10B (Fig. 3).
rs369156948 is a nonsense mutation in MPL.
This deletion spans chr15:102.15–102.22Mb (hg19) and is tagged by rs182643535.