Table 1.
Significant Novel Associations in PheWAS of Penn Medicine BioBank.
| Variant | Novel associations | Replication | ||||||
|---|---|---|---|---|---|---|---|---|
| Gene (SNP, uORF effect) | Phenotype (Phecode) | OR (95% CI) | P value | Cases | Controls | UKB | PMBB LOF | UKBB LOF |
| PMVK* (rs181302437) UAG > UAA | 250.13 (T1D - ophthalmic manifestations) | 27.29 (6.88-108.29) | 2.58E-06 | 23 | 5189 | No | No | Yes (250.13, P = 7.27e-03) |
| 250.14 (T1D - neurological manifestations) | 22.71 (5.86-87.97) | 6.20E-06 | 25 | 5189 | No | No | No | |
| 250.22 (T2D - renal manifestations) | 7.79 (2.87-21.17) | 5.73E-05 | 136 | 5189 | No | No | No | |
| VPS53 (rs35915949) UGA > UAA | 300.10 (Anxiety disorder) | 0.64 (0.53-0.77) | 4.23E-06 | 1060 | 6939 | No | No | No |
| 300.00 (Anxiety disorders) | 0.69 (0.58-0.82) | 2.00E-05 | 1249 | 6939 | No | No | No | |
| NALCN (rs139848407) CAA > UAA | 270.33 (Amyloidosis) | 38.92 (7.49-202.36) | 1.34E-05 | 30 | 7727 | No | No | Yes (270.00, P = 0.0264) |
| BCL2L13† (rs140799351) UGA > UAA | 610.00 (Benign mammary dysplasias) | 270.57 (19.69-3718.08) | 2.80E-05 | 55 | 7689 | No | Insufficient variants | Insufficient variants |
| 187.20 (Malignmant neoplasm of the testes) | 331.41 (21.68-5065.35) | 3.03E-05 | 26 | 7700 | Yes (187.20, P = 2.09e-4) | Insufficient variants | Insufficient variants | |
| 187.00 (Cancer of other male genital organs) | 220.01 (15.67-3089.83) | 6.31E-05 | 34 | 7700 | Yes (187.00, P = 3.33e-4) | Insufficient variants | Insufficient variants | |
| SHMT2 (rs28365863) UAG > UAA | 527.00 (Diseases of the salivary glands) | 6.37 (2.60-15.65) | 5.27E-05 | 90 | 9774 | Insufficient cases | Yes (527.00, P = 5.515e-03) | Insufficient cases |
| MOAP1 (rs116450723) UAC > UAA | 350.00 (Abnormal movement) | 4.99 (2.20-11.33) | 1.22E-04 | 362 | 9414 | No (variant not present in UKB) | No | No (variant not present in UKB) |
*As of the Gencode 32 release the 5′UTR PMVK annotation (September 2019) was shortened to exclude this uORF; however inspection of the raw ribosome profiling reads from Ji et al.16 in conjunction with nearby transcription start sites annotated in FANTOM5 confirm the presence of a longer PMVK 5′UTR isoform (Supplementary Fig. 7).
†The stop-strengthening variant in BCL2L13 affects a minor transcript isoform, and is also annotated as a synonymous mutation on the primary BCL2L13 transcript.