Table 2.
Results from main, sensitivity and stratified instrumental variable analyses on the association between Mexican Native American ancestry and breast cancer risk
| Method1 | # IV | Exp. var.2 (%) | OR | 95% CI | p-val | Q p-val3 | intercept p-val4 | ||
|---|---|---|---|---|---|---|---|---|---|
| Main analysis | |||||||||
| Two-sample MR | IVW | 134 | 38.5 | 0.988 | 0.987 | 0.990 | 1.4 × 10–44 | > 0.99 | |
| Sensitivity analyses | |||||||||
| Two-sample MR | Egger | 134 | 38.5 | 0.990 | 0.983 | 0.996 | 2.6 × 10–03 | > 0.99 | 0.66 |
| Two-sample MR | WM | 134 | 38.5 | 0.988 | 0.986 | 0.991 | 5.0 × 10–22 | ||
| expl. Variance ~ 8%5 | IVW | 17 | 8.4 | 0.990 | 0.986 | 0.993 | 6.7 × 10–09 | 0.94 | |
| HGDP as reference6 | IVW | 133 | 37.9 | 0.988 | 0.987 | 0.990 | 7.4 × 10–44 | > 0.99 | |
| refined Mexican reference7 | IVW | 134 | 38.6 | 0.988 | 0.987 | 0.990 | 7.7 × 10–44 | > 0.99 | |
| Stratified analyses | |||||||||
| BC diagnosed ≤ 45 y8 | IVW | 136 | 39.3 | 0.994 | 0.991 | 0.997 | 1.4 × 10–04 | > 0.99 | |
| Familial BC9 | IVW | 132 | 37.4 | 0.973 | 0.969 | 0.978 | 1.0 × 10–33 | > 0.99 | |
| ER-positive BC10 | IVW | 135 | 38.5 | 0.989 | 0.986 | 0.991 | 6.6 × 10–18 | > 0.99 | |
| ER-negative BC | IVW | 139 | 40.2 | 1.004 | 1.001 | 1.008 | 1.5 × 10–02 | > 0.99 | |
| Triple-negative BC11 | IVW | 142 | 40.3 | 1.004 | 0.999 | 1.009 | 0.11 | > 0.99 | |
Bold values indicate that the probability value is below 0.05
1IVW: Inverse variance weighted; Egger: MR-Egger regression; WM: weighted median estimates
2Exp. var.: Variance explained by the instrumental variables
3Cochran’s Q statistic p-values higher than 0.05 are suggestive of no instrument heterogeneity as a proxy for pleiotropy
4MR-Egger intercept p-values higher than 0.05 are consistent with no horizontal pleiotropy
5Subset of 17 IV explaining a cumulative variance in global proportion of Native American ancestry similar to the one in the Colombian study (8%)
6Individuals from the Human Genome Diversity Project were used instead of the 177 Native Americans from Mexico as the reference panel for estimation of global ancestry proportions
7The Maya, Mixe, Mixtec, Purepecha and Zapotec populations in the Human Genome Diversity Project were used as the reference panel for estimation of global ancestry proportions
8Breast cancer diagnosed before the age of 45 years
9Breast cancer patients with first-degree relatives affected by breast and/or ovarian cancer
10Oestrogen receptor-positive breast cancer
11Oestrogen receptor-negative, progesterone receptor-negative and human epidermal growth factor receptor-negative breast cancer