Table 2.
Association of MYBPC3 and MYH7 gene burdens with HCM in PMBB
| Gene burden | P | Beta | SE | OR | MYBPC3 Carrier N | HCM N |
|---|---|---|---|---|---|---|
| ClinVar P/LP (pLOF only) | 4.70E-10 | 6.792 | 1.09 | 890.907 | 18 | 6 |
| ClinVar P/LP (missense only) | 3.43E-04 | 2.766 | 0.773 | 15.891 | 27 | 2 |
| ClinVar P/LP (pLOF + missense) | 3.15E-20 | 4.177 | 0.453 | 65.161 | 45 | 8 |
| pLOF only | 1.52E-35 | 5.112 | 0.411 | 166.008 | 45 | 15 |
| pDM (REVEL ≥ 0.6) only | 4.05E-03 | 0.908 | 0.316 | 2.48 | 628 | 10 |
| pDM (4/4 algorithms) only | 1.43E-01 | 0.514 | 0.351 | 1.671 | 859 | 8 |
| pLOF + pDM (REVEL ≥ 0.6) | 7.99E-20 | 1.949 | 0.214 | 7.023 | 673 | 25 |
| pLOF + adjudicated missense (SHaRe) | 1.03E-42 | 4.402 | 0.321 | 81.638 | 67 | 17 |
| Gene burden | P | Beta | SE | OR | MYH7 Carrier N | HCM N |
| ClinVar P/LP (pLOF only) | 9.78E-01 | −7.803 | 277.662 | 4.08E-04 | 2 | 0 |
| ClinVar P/LP (missense only) | 1.25E-55 | 4.767 | 0.303 | 117.543 | 75 | 22 |
| ClinVar P/LP (pLOF + missense) | 1.29E-55 | 4.737 | 0.301 | 114.039 | 77 | 22 |
| pLOF only | 9.73E-01 | −10.658 | 315.401 | 2.35E-05 | 27 | 0 |
| pDM (REVEL ≥ 0.5) only | 2.01E-29 | 2.059 | 0.183 | 7.839 | 858 | 37 |
| pDM (4/4 algorithms) only | 2.99E-19 | 2.146 | 0.239 | 8.553 | 442 | 22 |
| pLOF + pDM (REVEL ≥ 0.5) | 9.23E-29 | 2.033 | 0.183 | 7.635 | 885 | 37 |
Note: Summary statistics for gene burden associations with HCM (combining Phecodes ‘Hypertrophic obstructive cardiomyopathy’ and ‘Other hypertrophic cardiomyopathy’) in PMBB by using ClinVar P/LP, pLOF only, missense only (pDM and/or adjudicated) and pLOF + missense variants in MYBPC3 (top) and MYH7 (bottom). Each gene burden association is reported as beta, standard error (SE), odds ratio (OR), P-value, the number of carriers for variants included in the gene burden and the number of carriers having the HCM phenotype.