Table 1.
High-confidence missense variants for blood pressure association signals (PP > 0.95)
Signal ID | Index SNV | Missense variant | Canonical transcript | Annotation | Chr | Position | PolyPhen | SIFT | Trait | p value | Posterior probability (%) |
---|---|---|---|---|---|---|---|---|---|---|---|
1_6 | rs262695 | rs262695 | ENST00000545087.1 | AL590822.1 p.Cys78Arg | 1 | 2,144,788 | N/A | N/A | SBP | 9.40 × 10−14 | 96.2 |
108_1 | rs1047891 | rs1047891 | ENST00000430249.2 | CPS1 p.Thr1412Asn | 2 | 211,540,507 | benign | tolerated | SBP | 1.40 × 10−14 | 98.5 |
DBP | 8.20 × 10−14 | 99.5 | |||||||||
132_2 | rs74951356 | rs74951356a | ENST00000418109.1 | LAMB2 p.Ala1765Thr | 3 | 49,158,763 | benign | tolerated | DBP | 5.00 × 10−09 | 95.8 |
158_3 | rs61762319 | rs61762319a | ENST00000460393.1 | MME p.Met8Val | 3 | 154,801,978 | benign | deleterious | SBP | 1.50 × 10−09 | 99.8 |
170_6 | rs2498323 | rs2498323 | ENST00000382774.3 | HGFAC p.Arg644Gln | 4 | 3,451,109 | possibly damaging | tolerated | PP | 7.40 × 10−13 | 100 |
191_3 | rs13107325 | rs13107325 | ENST00000394833.2 | SLC39A8 p.Ala391Thr | 4 | 103,188,709 | possibly damaging | tolerated | SBP | 4.20 × 10−53 | 100 |
221_1 | rs2307111 | rs2307111 | ENST00000428202.2 | POC5 p.His36Arg | 5 | 75,003,678 | benign | tolerated | DBP | 1.60 × 10−22 | 97.6 |
237_7 | rs1800888 | rs1800888a | ENST00000305988.4 | ADRB2 p.Thr164Ile | 5 | 148,206,885 | benign | tolerated | DBP | 7.40 × 10−13 | 100 |
249_1 | rs1800730 | rs1800730 | ENST00000357618.5 | HFE p.Ser65Cys | 6 | 26,091,185 | probably damaging | deleterious | SBP | 2.00 × 10−09 | 96.4 |
249_3 | rs1800562 | rs1800562a | ENST00000357618.5 | HFE p.Cys282Tyr | 6 | 26,093,141 | probably damaging | deleterious | DBP | 2.10 × 10−37 | 96.4 |
251_7 | rs41543814 | rs41543814 | ENST00000376228.5 | HLA-C p.Ala97Thr | 6 | 31,239,430 | benign | tolerated (LC) | DBP | 1.50 × 10−19 | 100 |
251_10 | rs2844573 | rs2308655 | ENST00000412585.2 | HLA-B p.Cys349Ser | 6 | 31,322,303 | benign | tolerated (LC) | PP | 1.40 × 10−12 | 99.2 |
252_1 | rs3176336 | rs2395655 | ENST00000448526.2 | CDKN1A p.Asp28Gly | 6 | 36,645,696 | benign | tolerated (LC) | PP | 4.70 × 10−13 | 98.5 |
255_1 | rs78648104 | rs78648104 | ENST00000008391.3 | TFAP2D p.Phe74Leu | 6 | 50,683,009 | benign | tolerated | SBP | 2.40 × 10−15 | 99.9 |
272_1 | rs6919947 | rs6919947 | ENST00000368357.3 | NCOA7 p.Ser399Ala | 6 | 126,210,395 | benign | tolerated (LC) | SBP | 4.90 × 10−17 | 100 |
300_3 | rs2854746 | rs2854746 | ENST00000381083.4 | IGFBP3 p.Ala32Gly | 7 | 45,960,645 | benign | tolerated | DBP | 5.00 × 10−11 | 97.9 |
313_2 | rs11556924 | rs11556924 | ENST00000358303.4 | ZC3HC1 p.Arg363His | 7 | 129,663,496 | probably damaging | deleterious | DBP | 1.50 × 10−26 | 98.3 |
365_2 | rs76452347 | rs76452347 | ENST00000354323.2 | HRCT1 p.Arg63Trp | 9 | 35,906,471 | possibly damaging | deleterious (LC) | SBP | 7.10 × 10−14 | 100 |
379_2 | rs6271 | rs6271a,b | ENST00000393056.2 | DBH p.Arg549Cys | 9 | 136,522,274 | possibly damaging | tolerated | SBP | 1.20 × 10−19 | 97.6 |
394_1 | rs2236295 | rs2236295 | ENST00000373783.1 | ADO p.Gly25Trp | 10 | 64,564,892 | possibly damaging | tolerated | SBP | 2.80 × 10−22 | 96.7 |
402_3 | rs2274224 | rs2274224b | ENST00000371380.3 | PLCE1 p.Arg1575Pro | 10 | 96,039,597 | benign | tolerated | SBP | 9.00 × 10−57 | 96.6 |
417_10 | rs10770059 (SBP) | rs415895 | ENST00000318950.6 | SWAP70 p.Gln505Glu | 11 | 9,769,562 | benign | tolerated | SBP | 5.00 × 10−47 | 96.5 |
432_4 | rs117874826 | rs117874826a,b | ENST00000540288.1 | PLCB3 p.Glu564Ala | 11 | 64,027,666 | benign | deleterious | SBP | 2.30 × 10−11 | 100 |
434_1 | rs36027301 | rs36027301 | ENST00000265686.3 | TCIRG1 p.Arg56Trp | 11 | 67,809,268 | probably damaging | deleterious | SBP | 6.00 × 10−11 | 97.6 |
447_7 | rs573455 | rs573455 | ENST00000278935.3 | CEP164 p.Gln1119Arg | 11 | 117,267,884 | benign | tolerated | PP | 8.70 × 10−34 | 100 |
463_15 | rs1126930 | rs1126930a | ENST00000316299.5 | PRKAG1 p.Thr98Ser | 12 | 49,399,132 | benign | tolerated | PP | 4.60 × 10−14 | 95.6 |
499_1 | rs17880989 | rs17880989 | ENST00000311852.6 | MMP14 p.Met355Ile | 14 | 23,313,633 | benign | deleterious | DBP | 3.20 × 10−12 | 100 |
572_1 | rs704 | rs704 | ENST00000226218.4 | VTN p.Thr400Met | 17 | 26,694,861 | benign | tolerated | SBP | 1.90 × 10−08 | 96.5 |
582_6 | rs34587622 | rs34587622 | ENST00000427177.1 | SEPT9 p.Pro145Leu | 17 | 75,398,498 | benign | tolerated (LC) | SBP | 6.20 × 10−14 | 99.9 |
606_9 | rs167479 | rs167479 | ENST00000393423.3 | RGL3 p.Pro162His | 19 | 11,526,765 | probably damaging | deleterious | SBP | 8.70 × 10−69 | 100 |
610_2 | rs45522544 | rs45522544 | ENST00000357324.6 | ATP13A1 p.Glu556Lys | 19 | 19,765,499 | benign | tolerated | DBP | 3.10 × 10−08 | 100 |
616_4 | rs34093919 | rs34093919 | ENST00000308370.7 | LTBP4 p.Asp752Asn | 19 | 41,117,300 | possibly damaging | deleterious | PP | 2.80 × 10−14 | 97.4 |
616_7 | rs1800470 | rs1800470 | ENST00000221930.5 | TGFB1 p.Pro10Leu | 19 | 41,858,921 | N/A | tolerated (LC) | PP | 1.90 × 10−15 | 99 |
617_2 | rs7412 | rs7412 | ENST00000252486.4 | APOE p.Arg176Cys | 19 | 45,412,079 | probably damaging | deleterious | SBP | 2.00 × 10−14 | 100 |
623_3 | rs35761929 | rs35761929 | ENST00000254958.5 | JAG1 p.Pro871Arg | 20 | 10,622,501 | benign | deleterious | DBP | 2.60 × 10−18 | 99.1 |
636_1 | rs2229742 | rs2229742 | ENST00000400202.1 | NRIP1 p.Arg448Gly | 21 | 16,339,172 | probably damaging | deleterious | SBP | 7.40 × 10−16 | 100 |
PP | 2.30 × 10−11 | 99.7 |
SNV, single-nucleotide variant; Chr, chromosome; SIFT, sorting intolerant from tolerant algorithm, which predicts the effect of coding variants on protein function; PolyPhen, polymorphism phenotyping tool predicts possible impact of an amino acid substitution on the structure and function of a human protein; posterior probability, the SNV’s accounted posterior probability of driving the blood pressure association under the annotation-informed prior.
Indicates a low frequency variant (our data and in non-Finnish Europeans, https://gnomad.broadinstitute.org).