Table 3 |.
PheWAS of two pLoF variants in MVP participants of European ancestry
| Gene | RSID | Amino acid change | PheWAS phenotype | P | n Cases | n Controls | OR | 95%CIlower | 95%CIupper |
|---|---|---|---|---|---|---|---|---|---|
| ANKDD1B | rs34358 | p.Trp480* | Diabetes mellitus | 1.04E-06 | 62,930 | 104,442 | 0.96 | 0.95 | 0.98 |
| Type 2 diabetes | 1.36E-06 | 62,531 | 104,442 | 0.96 | 0.95 | 0.98 | |||
| T2D with neurological manifestations | 1.63E-05 | 14,159 | 104,442 | 0.94 | 0.92 | 0.97 | |||
| Disorders of lipid metabolism | 5.03E-08 | 141,535 | 41,406 | 1.05 | 1.03 | 1.07 | |||
| Hyperlipidemia | 4.66E-08 | 141,408 | 41,406 | 1.05 | 1.03 | 1.07 | |||
| Hypercholesterolemia | 2.33E-06 | 32,008 | 41,406 | 1.06 | 1.03 | 1.08 | |||
| CCHCR1 | rs3130453 | p.Trp78* | Diabetes mellitus | 4.26E-05 | 62,930 | 104,442 | 0.97 | 0.96 | 0.98 |
| Type 1 diabetes | 3.99E-07 | 6,566 | 104,442 | 0.91 | 0.88 | 0.95 | |||
| Type 2 diabetes | 3.96E-05 | 62,531 | 104,442 | 0.97 | 0.96 | 0.98 | |||
| Epistaxis or throat hemorrhage | 1.96E-05 | 2,751 | 110,902 | 1.12 | 1.07 | 1.19 | |||
| Celiac disease | 2.72E-19 | 418 | 124,470 | 0.52 | 0.45 | 0.60 | |||
| Microscopic hematuria | 1.83E-05 | 4,078 | 147,054 | 1.1 | 1.05 | 1.15 | |||
| Psoriatic arthropathy | 7.82E-10 | 1,077 | 140,876 | 0.76 | 0.70 | 0.83 |
The pLoF variants were tested using logistic regression adjusting for age, sex, and 10 principal components in an additive effects model using the PheWAS R package in R v3.2.0. Phenotypes were required to have a case count over 25 in order to be included in the PheWAS, and a multiple testing thresholds for statistical significance was set to the Bonferroni-corrected P-value threshold of 2.8 × 10−5. pLOF, predicted loss-of-function; RSID, RefSNP identification number; PheWAS, phenome-wide association study; n Cases, number of cases with PheWAS phenotype; n Controls, number of unaffected controls for the respective PheWAS phenotype; OR, odds ratio; CI, confidence interval; T2D, type 2 diabetes.