Table 2.
Summary of allele frequency differences between cases and controls.
| Cases | Controls | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| OMGL | HCMR | Total cases | P-value* | BRRD | gnomAD exomes | gnomAD genomes | Total gnomAD | TOPMED | Total Controls† | OR (95% CI) | Fisher’s P-value‡ | |
| MYBPC3−52minor allele frequency | ||||||||||||
| Global | 0.00580 [0.00574 – 0.00587] (32/2,757) | 0.00436 [0.00431 – 0.00442] (23/2,636) | 0.00510 [0.00506 – 0.00514] (55/5,393) | 0.359 | − [0–3.25 × 10−7] (0/6,056) | −(0/0) | 3.2 × 10−5 [9.56 × 10−5 - 3.40 × 10−5] (1/15,667) | 3.2 × 10−5 [9.56 × 10−5 - 3.40 × 10−5] (1/15,667) | − [0–3.13 × 10−8] (0/62,784) | 6.57 × 10−6 [1.97 × 10−5 - 7.00 × 10−6] (1/76,048) | 780 (135 – 16,384) | 5.77 × 10−64 |
| European (NFE) | NA | 0.00410 [0.00404 – 0.00416] (17/2,074) | 0.00410 [0.00404 – 0.00416] (17/2,074) | - | − [0–5.45 × 10−7] (0/3,606) | − (0/0) | − [0–2.55 × 10−7] (0/7,696) | − [0–2.55 × 10−7] (0/7,696) | No ancestry data | − [0–2.55 × 10−7] (0/7,696) | ∞ (15.4 – ∞) | 3.43 × 10−12 |
| South Asian | NA | 0.0224 [0.0218 – 0.0230] (6/134) | 0.0224 [0.0218 – 0.0230] (6/134) | - | − [0–5.20 × 10−6] (0/378) | − (0/0) | − (0/0) | − (0/0) | No ancestry data | − (0/0) | - | - |
| MYBPC3Δ25minor allele frequency | ||||||||||||
| Global | 0.00363 [0.00358 – 0.00368] (20/2,757) | 0.00341 [0.00336 – 0.00347] (18/2,636) | 0.00352 [0.00349 – 0.00356] (38/5,393) | 0.98 | 0.00182 [0.00179 – 0.00184] (22/6,056) | 0.00394 [0.00393 – 0.00394] (978/124,259) | 9.56 × 10−5 [9.22 × 10−5 - 9.91 × 10−5] (3/15,695) | 0.00350 [0.00350 – 0.00351] (981/139,954) | 2.39 × 10−5 [2.30 × 10−5 - 2.48 × 10−5] (3/62,784) | 0.00250 [0.00249 – 0.00250] (984/197,114) | 1.41 (0.99 – 1.96) | 0.040 |
| European (NFE) | NA | − [0–9.48 × 10−7] (0/2,074) | − [0–9.48 × 10−7] (0/2,074) | - | − [0–5.45 × 10−7] (0/3,606) | 8.90 × 10−6 [2.67 × 10−5 - 9.47 × 10−6] (1/56,194) | − [0–2.55 × 10−7] (0/7,708) | 7.82 × 10−6 [2.34 × 10−5-8.33 × 10−6] (1/63,902) | No ancestry data | 7.82 × 10−6 [2.34 × 10−5-8.33 × 10−6] (1/63,902) | - | - |
| South Asian | NA | 0.0634 [0.0625 – 0.0644] (17/134) | 0.0634 [0.0625 – 0.0644] (17/134) | - | 0.0278 [0.0274 – 0.0282] (21/378) | 0.0314 [0.0314 – 0.0315] (962/15,296) | − (0/0) | 0.0321 [0.0320 – 0.0321] (981/15,296) | No ancestry data | 0.0321 [0.0320 – 0.0321] (981/15,296) | 1.98 (1.11 – 3.50) | 0.015 |
Minor allele frequency [95% binomial confidence interval calculated using Wilson’s method] presented with variant carrier counts in parentheses () beneath. BRRD: BioResource for Rare Disease cohort; gnomAD: genome aggregation database; HCMR: Hypertrophic Cardiomyopathy Registry; NFE: Non-Finnish European; OMGL: Oxford Medical Genetics Laboratory; TOPMED: Trans-Omics for Precision Medicine.
OMGL and HCMR case proportions compared using 2-sample test for equality of proportions with continuity correction.
total controls calculated from non-overlapping samples provided by gnomAD and TOPMED.
Fisher’s P-value relates to the hypothesis that cases, derived from the OMGL and HCMR cohorts, are enriched for either MYBPC3−52 or MYBPC3Δ25 when compared with non-overlapping controls, provided by gnomAD and TOPMED.