Table 2 Identified alleles in pharmacogenes and the carrier frequency of associated actionable phenotypes among Singaporeans in the SG10K_Health cohort
From: Analysis of clinically relevant variants from ancestrally diverse Asian genomes
Gene | Risk allele(s) | Phenotype | No. risk allele carriers/Total individuals genotyped (%) | |||
|---|---|---|---|---|---|---|
CH | IND | MY | All | |||
CACNA1S | decreased func.: rs772226819 | MHS | 0/5377 | 0/1891 | 1/1571 (0.1%) | 1/8839 (0.01%) |
CFTR | rs115545701, rs202179988, rs78769542, rs74503330 | Responsive to ivacaftor | 9/5239 (0.2%) | 15/1796 (0.8%) | 7/1509 (0.5%) | 31/8544 (0.4%) |
CYP2B6 | increased func.: *4, *22 | UM | 53/5452 (1.0%) | 12/1926 (0.6%) | 3/1594 (0.2%) | 68/8972 (0.8%) |
decreased func.: *6, *7, *9, *19, *26, *36 | RM | 596/5452 (10.9%) | 124/1926 (6.4%) | 68/1594 (4.3%) | 788/8972 (8.8%) | |
no func.: *8, *12, *13, *18, *24 | IM | 1690/5452 (31.0%) | 819/1926 (42.5%) | 705/1594 (44.2%) | 3214/8972 (35.8%) | |
PM | 315/5452 (5.8%) | 320/1926 (16.6%) | 257/1594 (16.1%) | 892/8972 (9.9%) | ||
CYP2C9 | decreased func.: *2, *8, *11, *14, *16, *29, *31, *37, *44, *50, *55 | IM | 408/5452 (7.5%) | 440/1926 (22.9%) | 119/1595 (7.5%) | 967/8973 (10.8%) |
no func.: *3, *13, *33,*39, *42, *45, *52 | PM | 14/5452 (0.3%) | 50/1926 (2.6%) | 5/1595 (0.3%) | 69/8973 (0.8%) | |
CYP2C19 | increased func.: *17 | UM/RM | 51/5452 (0.9%) | 280/1926 (14.5%) | 54/1595 (3.4%) | 385/8973 (4.3%) |
decreased func.: *10, *16, *26 | IM | 2434/5452 (44.6%) | 881/1926 (45.7%) | 619/1595 (38.8%) | 3934/8973 (43.8%) | |
no func.:*2, *3, *4, *5, *6, *8, *24, *35 | PM | 765/5452 (14.0%) | 326/1926 (16.9%) | 140/1595 (8.8%) | 1231/8973 (13.7%) | |
CYP2D6 | increased func.: *1 × 2, *1 × 3, *2 × 2 | UM | 51/3870 (1.3%) | 39/1481 (2.6%) | 13/1124 (1.2%) | 103/6475 (1.6%) |
decreased func.: *9, *10, *10 × 2, *10 × 2 + *83, *14, *17, *29, *41, *49, *49 × 2, *36-*10, *36 × 2-*10, *36 × 2-*10-*83, *36 + *10 × 2 + *83 | IM | 1667/3870 (43.1%) | 366/1481 (24.7%) | 413/1124 (36.7%) | 2446/6475 (37.8%) | |
no func.: *3, *4, *4 N, *4 + *4 N, *4 + *68, *5, *6, *7, *13, *15, *21, *21 × 2, *31, *36, *36 × 2, *36 × 3, *68, *69, *99, *101, *114 | PM | 110/3870 (2.8%) | 55/1481 (3.7%) | 66/1124 (5.9%) | 231/6475 (3.6%) | |
CYP3A4 | decreased func.: *22 | Decreased metabolism | 0/5452 | 18/1926 (0.9%) | 6/1595 (0.4%) | 24/8973 (0.3%) |
CYP3A5 | normal func.: *1 | NM | 534/5448 (9.8%) | 291/1917 (15.2%) | 251/1562 (16.1%) | 1076/8927 (12.1%) |
no func.: *3, *6, *7 | IM | 2029/5448 (37.2%) | 765/1917 (39.9%) | 706/1562 (45.2%) | 3500/8927 (39.2%) | |
PM | 2688/5448 (49.3%) | 844/1917 (44.0%) | 589/1562 (37.7%) | 4121/8927 (46.2%) | ||
CYP4F2 | decreased func.: rs2108622 | Increased warfarin dose requirement | 2178/5283 (41.2%) | 1252/1839 (68.1%) | 531/1548 (34.3%) | 3961/8670 (45.7%) |
DPYD | decreased func.: HapB3, rs186169810, rs112766203 | IM | 39/5445 (0.7%) | 82/1915 (4.3%) | 4/1562 (0.3%) | 125/8922 (1.4%) |
no func.: *2, *8, rs72549304, rs59086055, rs138616379, rs55674432, rs72549308, rs3918290 | PM | 0/5445 | 0/1915 | 1/1562 (0.1%) | 1/8922 (0.01%) | |
F5 | rs6025 | Increased risk of VTE | 2/5378 (0.04%) | 44/1872 (2.4%) | 6/1565 (0.4%) | 52/8815 (0.6%) |
G6PD | WHO Class II, III deficient alleles a | Deficient | 53/5502 (1.0%) | 18/1941 (0.9%) | 16/1608 (1.0%) | 87/9051 (1.0%) |
Variable | 179/5502 (3.3%) | 34/1941 (1.8%) | 44/1608 (2.7%) | 257/9051 (2.8%) | ||
HLA-A | deficient: A*31:01:02 | Increased risk of SCAR | 147/5468 (2.7%) | 99/1919 (5.2%) | 11/1596 (0.7%) | 257/8983 (2.9%) |
HLA-B | deficient: B*15:02:01, B*58:01 | Increased risk of SCAR | 1452/5468 (26.6%) | 200/1918 (10.4%) | 441/1596 (27.6%) | 2093/8982 (23.3%) |
deficient: B*57:01:01 | Abacavir hypersensitivity | 33/5468 (0.6%) | 265/1918 (13.8%) | 28/1596 (1.8%) | 326/8982 (3.6%) | |
IFNL3 | decreased response: rs12979860, rs8099917 | Decreased response to peginterferon alfa-2a/2b | 620/5168 (12.0%) | 750/1801 (41.6%) | 197/1520 (13.0%) | 1567/8489 (18.5%) |
IFNL4 | decreased response: rs12979860, rs11322783 | Decreased response to peginterferon alfa-2a/2b | 603/5079 (11.9%) | 748/1768 (42.3%) | 198/1521 (13.0%) | 1549/8368 (18.5%) |
NAT2 | rapid allele: *4 | Rapid acetylator | 1452/5452 (26.6%) | 119/1925 (6.2%) | 248/1595 (15.6%) | 1819/8972 (20.3%) |
slow allele: *5, *6, *6 A, *7, *7B | Intermediate acetylator | 2252/5452 (41.3%) | 340/1925 (17.7%) | 537/1595 (33.7%) | 3129/8972 (34.9%) | |
Slow acetylator | 1015/5452 (18.6%) | 404/1925 (21.0%) | 390/1595 (24.5%) | 1809/8972 (20.2%) | ||
NUDT15 | no func.: rs116855232 | IM | 1037/5362 (19.3%) | 265/1883 (14.1%) | 183/1560 (11.7%) | 1485/8805 (16.9%) |
PM | 52/5362 (1.0%) | 13/1883 (0.7%) | 13/1560 (0.8%) | 78/8805 (0.9%) | ||
RYR1 | increased func.: rs112563513, rs121918593, rs118192168 | MHS | 4/4947 (0.1%) | 1/1727 (0.1%) | 0/1486 | 5/8160 (0.1%) |
SLCO1B1 | decreased func.: rs4149056 | Intermediate risk of statin-related myopathy | 1092/5366 (20.4%) | 268/1896 (14.1%) | 250/1575 (15.9%) | 1610/8837 (18.2%) |
Increased risk of statin-related myopathy | 69/5366 (1.3%) | 2/1896 (0.1%) | 11/1575 (0.7%) | 82/8837 (0.9%) | ||
TPMT | no func.: *3, *3 A, *3 C, *29 | IM | 124/4297 (2.9%) | 32/1245 (2.6%) | 52/1206 (4.3%) | 208/6748 (3.1%) |
PM | 0/4297 | 1/1245 (0.1%) | 3/1206 (0.3%) | 4/6748 (0.1%) | ||
UGT1A1 | increased func.: *3 | IM | 1737/4341 (40.0%) | 809/1492 (54.2%) | 332/1201 (27.6%) | 2878/7034 (40.9%) |
decreased func.: *6, *28, *37, *80 + *28, *80 + *37 | PM | 140/4341 (3.2%) | 259/1492 (17.4%) | 16/1201 (1.3%) | 415/7034 (5.9%) | |
VKORC1 | rs9923231, rs7294, rs2359612, rs9934438 | Higher warfarin sensitivity | 4569/4630 (98.7%) | 428/1507 (28.4%) | 1282/1348 (95.1%) | 6279/7485 (83.9%) |
