Significant gene-centric and genetic region rare variant set analysis (after conditioning on known variants from the GWAS catalog and single-variant signals in the present analysis).
| Gene Centric Analysis . | ||||||||
|---|---|---|---|---|---|---|---|---|
| Trait . | CHR . | Symbol . | category . | # variants . | cMAC . | STAAR-O p-value . | ||
| unconditional . | conditional . | cond2round . | ||||||
| C-Reactive Protein (CRP) | 1 | CRP | missense | 54 | 336 | 3.6E-22 | 1.3E-08 | |
| Lipoprotein-associated phospholipase A2 (Lp-PLA2) Activity | 6 | PLA2G7 | pLOF | 5 | 14 | 1.3E-13 | 1.1E-13 | 1.6E-06 |
| 6 | PLA2G7 | missense | 56 | 323 | 6.4E-78 | 8.5E-28 | 3.9E-23 | |
| Lipoprotein-associated phospholipase A2 (Lp-PLA2) Mass | 6 | PLA2G7 | pLOF | 5 | 13 | 1.7E-10 | 1.1E-10 | |
| 6 | PLA2G7 | missense | 55 | 326 | 1.8E-75 | 1.1E-18 | ||
| Intercellular Adhesion Molecule 1 (ICAM-1) | 19 | ICAM1 | missense | 69 | 451 | 7.8E-15 | 5.0E-08 | 3.9E-05 |
| 19 | ZNF653 | enhancer | 126 | 577 | 2.3E-11 | 2.3E-11 | 8.7E-01 | |
| Region-Based Analysis | ||||||||
| Trait | CHR | pos_min | pos_max | # variants | cMAC | STAAR-O p-value | ||
| unconditional | conditional | cond2round | ||||||
| Lipoprotein-associated phospholipase A2 (Lp-PLA2) Activity | 6 | 46707812 | 46709811 | 103 | 526 | 2.2E-46 | 1.7E-20 | 9.1E-10 |
| 6 | 46708812 | 46710811 | 95 | 389 | 6.9E-74 | 1.3E-21 | 4.2E-11 | |
| Lipoprotein-associated phospholipase A2 (Lp-PLA2) Mass | 6 | 46707812 | 46709811 | 103 | 532 | 5.3E-44 | 9.3E-14 | |
| 6 | 46708812 | 46710811 | 94 | 394 | 1.3E-64 | 2.0E-14 | ||
| Intercellular Adhesion Molecule 1 (ICAM-1) | 19 | 11282547 | 11284546 | 68 | 591 | 6.1E-12 | 4.5E-10 | 6.8E-01 |
| 19 | 11283547 | 11285546 | 91 | 892 | 7.7E-12 | 5.6E-10 | 9.7E-01 | |
| 19 | 11284547 | 11286546 | 96 | 1337 | 1.8E-09 | 7.0E-09 | 6.5E-01 | |
| 19 | 11285547 | 11287546 | 85 | 871 | 1.1E-09 | 1.8E-08 | 7.4E-01 | |
| 19 | 11503547 | 11505546 | 119 | 729 | 2.8E-11 | 2.8E-11 | 8.3E-01 | |
| 19 | 11504547 | 11506546 | 154 | 818 | 3.6E-11 | 3.6E-11 | 6.5E-01 | |
| P-selectin | 1 | 169615464 | 169617463 | 65 | 433 | 7.5E-12 | 3.6E-12 | 4.8E-07 |
| 1 | 169616464 | 169618463 | 66 | 363 | 4.6E-12 | 5.1E-12 | 5.6E-07 | |
| Gene Centric Analysis . | ||||||||
|---|---|---|---|---|---|---|---|---|
| Trait . | CHR . | Symbol . | category . | # variants . | cMAC . | STAAR-O p-value . | ||
| unconditional . | conditional . | cond2round . | ||||||
| C-Reactive Protein (CRP) | 1 | CRP | missense | 54 | 336 | 3.6E-22 | 1.3E-08 | |
| Lipoprotein-associated phospholipase A2 (Lp-PLA2) Activity | 6 | PLA2G7 | pLOF | 5 | 14 | 1.3E-13 | 1.1E-13 | 1.6E-06 |
| 6 | PLA2G7 | missense | 56 | 323 | 6.4E-78 | 8.5E-28 | 3.9E-23 | |
| Lipoprotein-associated phospholipase A2 (Lp-PLA2) Mass | 6 | PLA2G7 | pLOF | 5 | 13 | 1.7E-10 | 1.1E-10 | |
| 6 | PLA2G7 | missense | 55 | 326 | 1.8E-75 | 1.1E-18 | ||
| Intercellular Adhesion Molecule 1 (ICAM-1) | 19 | ICAM1 | missense | 69 | 451 | 7.8E-15 | 5.0E-08 | 3.9E-05 |
| 19 | ZNF653 | enhancer | 126 | 577 | 2.3E-11 | 2.3E-11 | 8.7E-01 | |
| Region-Based Analysis | ||||||||
| Trait | CHR | pos_min | pos_max | # variants | cMAC | STAAR-O p-value | ||
| unconditional | conditional | cond2round | ||||||
| Lipoprotein-associated phospholipase A2 (Lp-PLA2) Activity | 6 | 46707812 | 46709811 | 103 | 526 | 2.2E-46 | 1.7E-20 | 9.1E-10 |
| 6 | 46708812 | 46710811 | 95 | 389 | 6.9E-74 | 1.3E-21 | 4.2E-11 | |
| Lipoprotein-associated phospholipase A2 (Lp-PLA2) Mass | 6 | 46707812 | 46709811 | 103 | 532 | 5.3E-44 | 9.3E-14 | |
| 6 | 46708812 | 46710811 | 94 | 394 | 1.3E-64 | 2.0E-14 | ||
| Intercellular Adhesion Molecule 1 (ICAM-1) | 19 | 11282547 | 11284546 | 68 | 591 | 6.1E-12 | 4.5E-10 | 6.8E-01 |
| 19 | 11283547 | 11285546 | 91 | 892 | 7.7E-12 | 5.6E-10 | 9.7E-01 | |
| 19 | 11284547 | 11286546 | 96 | 1337 | 1.8E-09 | 7.0E-09 | 6.5E-01 | |
| 19 | 11285547 | 11287546 | 85 | 871 | 1.1E-09 | 1.8E-08 | 7.4E-01 | |
| 19 | 11503547 | 11505546 | 119 | 729 | 2.8E-11 | 2.8E-11 | 8.3E-01 | |
| 19 | 11504547 | 11506546 | 154 | 818 | 3.6E-11 | 3.6E-11 | 6.5E-01 | |
| P-selectin | 1 | 169615464 | 169617463 | 65 | 433 | 7.5E-12 | 3.6E-12 | 4.8E-07 |
| 1 | 169616464 | 169618463 | 66 | 363 | 4.6E-12 | 5.1E-12 | 5.6E-07 | |
Trait: trait name.
CHR: chromosome where the gene is located.
Symbol: gene symbols.
Category: category of gene-based test; pLOF means putative loss of function.
pos_min: starting position of the region tested, hg38.
pos_max: ending position of the region tested, hg38.
# variants: number of variants tested in the aggregate test.
cMAC: cumulative minor allele count.
STAAR-O P-value: P-values of aggregate tests in 3 cases.
unconditional: P-value of unconditional analysis.
conditional: P-value of conditional analysis conditioning on (1) variants reported on previous literature (Table S6), (2) lead signals from our conditional single variant association analysis.
cond2round: P-value of second round of conditional analysis: conditional list for second round conditional analysis consists of 2 parts: (1) conditional list for the first round conditional analysis; (2) additionally, variants included in the aggregate test which had nominally significant individual variant P-values (P < 1.0 × 10−6) (Tables S10A and S11A). Note that not all gene sets have such remaining significant variants, so we do not further perform the second round conditional analysis in these cases, and leave the column blank.
Significant gene-centric and genetic region rare variant set analysis (after conditioning on known variants from the GWAS catalog and single-variant signals in the present analysis).
| Gene Centric Analysis . | ||||||||
|---|---|---|---|---|---|---|---|---|
| Trait . | CHR . | Symbol . | category . | # variants . | cMAC . | STAAR-O p-value . | ||
| unconditional . | conditional . | cond2round . | ||||||
| C-Reactive Protein (CRP) | 1 | CRP | missense | 54 | 336 | 3.6E-22 | 1.3E-08 | |
| Lipoprotein-associated phospholipase A2 (Lp-PLA2) Activity | 6 | PLA2G7 | pLOF | 5 | 14 | 1.3E-13 | 1.1E-13 | 1.6E-06 |
| 6 | PLA2G7 | missense | 56 | 323 | 6.4E-78 | 8.5E-28 | 3.9E-23 | |
| Lipoprotein-associated phospholipase A2 (Lp-PLA2) Mass | 6 | PLA2G7 | pLOF | 5 | 13 | 1.7E-10 | 1.1E-10 | |
| 6 | PLA2G7 | missense | 55 | 326 | 1.8E-75 | 1.1E-18 | ||
| Intercellular Adhesion Molecule 1 (ICAM-1) | 19 | ICAM1 | missense | 69 | 451 | 7.8E-15 | 5.0E-08 | 3.9E-05 |
| 19 | ZNF653 | enhancer | 126 | 577 | 2.3E-11 | 2.3E-11 | 8.7E-01 | |
| Region-Based Analysis | ||||||||
| Trait | CHR | pos_min | pos_max | # variants | cMAC | STAAR-O p-value | ||
| unconditional | conditional | cond2round | ||||||
| Lipoprotein-associated phospholipase A2 (Lp-PLA2) Activity | 6 | 46707812 | 46709811 | 103 | 526 | 2.2E-46 | 1.7E-20 | 9.1E-10 |
| 6 | 46708812 | 46710811 | 95 | 389 | 6.9E-74 | 1.3E-21 | 4.2E-11 | |
| Lipoprotein-associated phospholipase A2 (Lp-PLA2) Mass | 6 | 46707812 | 46709811 | 103 | 532 | 5.3E-44 | 9.3E-14 | |
| 6 | 46708812 | 46710811 | 94 | 394 | 1.3E-64 | 2.0E-14 | ||
| Intercellular Adhesion Molecule 1 (ICAM-1) | 19 | 11282547 | 11284546 | 68 | 591 | 6.1E-12 | 4.5E-10 | 6.8E-01 |
| 19 | 11283547 | 11285546 | 91 | 892 | 7.7E-12 | 5.6E-10 | 9.7E-01 | |
| 19 | 11284547 | 11286546 | 96 | 1337 | 1.8E-09 | 7.0E-09 | 6.5E-01 | |
| 19 | 11285547 | 11287546 | 85 | 871 | 1.1E-09 | 1.8E-08 | 7.4E-01 | |
| 19 | 11503547 | 11505546 | 119 | 729 | 2.8E-11 | 2.8E-11 | 8.3E-01 | |
| 19 | 11504547 | 11506546 | 154 | 818 | 3.6E-11 | 3.6E-11 | 6.5E-01 | |
| P-selectin | 1 | 169615464 | 169617463 | 65 | 433 | 7.5E-12 | 3.6E-12 | 4.8E-07 |
| 1 | 169616464 | 169618463 | 66 | 363 | 4.6E-12 | 5.1E-12 | 5.6E-07 | |
| Gene Centric Analysis . | ||||||||
|---|---|---|---|---|---|---|---|---|
| Trait . | CHR . | Symbol . | category . | # variants . | cMAC . | STAAR-O p-value . | ||
| unconditional . | conditional . | cond2round . | ||||||
| C-Reactive Protein (CRP) | 1 | CRP | missense | 54 | 336 | 3.6E-22 | 1.3E-08 | |
| Lipoprotein-associated phospholipase A2 (Lp-PLA2) Activity | 6 | PLA2G7 | pLOF | 5 | 14 | 1.3E-13 | 1.1E-13 | 1.6E-06 |
| 6 | PLA2G7 | missense | 56 | 323 | 6.4E-78 | 8.5E-28 | 3.9E-23 | |
| Lipoprotein-associated phospholipase A2 (Lp-PLA2) Mass | 6 | PLA2G7 | pLOF | 5 | 13 | 1.7E-10 | 1.1E-10 | |
| 6 | PLA2G7 | missense | 55 | 326 | 1.8E-75 | 1.1E-18 | ||
| Intercellular Adhesion Molecule 1 (ICAM-1) | 19 | ICAM1 | missense | 69 | 451 | 7.8E-15 | 5.0E-08 | 3.9E-05 |
| 19 | ZNF653 | enhancer | 126 | 577 | 2.3E-11 | 2.3E-11 | 8.7E-01 | |
| Region-Based Analysis | ||||||||
| Trait | CHR | pos_min | pos_max | # variants | cMAC | STAAR-O p-value | ||
| unconditional | conditional | cond2round | ||||||
| Lipoprotein-associated phospholipase A2 (Lp-PLA2) Activity | 6 | 46707812 | 46709811 | 103 | 526 | 2.2E-46 | 1.7E-20 | 9.1E-10 |
| 6 | 46708812 | 46710811 | 95 | 389 | 6.9E-74 | 1.3E-21 | 4.2E-11 | |
| Lipoprotein-associated phospholipase A2 (Lp-PLA2) Mass | 6 | 46707812 | 46709811 | 103 | 532 | 5.3E-44 | 9.3E-14 | |
| 6 | 46708812 | 46710811 | 94 | 394 | 1.3E-64 | 2.0E-14 | ||
| Intercellular Adhesion Molecule 1 (ICAM-1) | 19 | 11282547 | 11284546 | 68 | 591 | 6.1E-12 | 4.5E-10 | 6.8E-01 |
| 19 | 11283547 | 11285546 | 91 | 892 | 7.7E-12 | 5.6E-10 | 9.7E-01 | |
| 19 | 11284547 | 11286546 | 96 | 1337 | 1.8E-09 | 7.0E-09 | 6.5E-01 | |
| 19 | 11285547 | 11287546 | 85 | 871 | 1.1E-09 | 1.8E-08 | 7.4E-01 | |
| 19 | 11503547 | 11505546 | 119 | 729 | 2.8E-11 | 2.8E-11 | 8.3E-01 | |
| 19 | 11504547 | 11506546 | 154 | 818 | 3.6E-11 | 3.6E-11 | 6.5E-01 | |
| P-selectin | 1 | 169615464 | 169617463 | 65 | 433 | 7.5E-12 | 3.6E-12 | 4.8E-07 |
| 1 | 169616464 | 169618463 | 66 | 363 | 4.6E-12 | 5.1E-12 | 5.6E-07 | |
Trait: trait name.
CHR: chromosome where the gene is located.
Symbol: gene symbols.
Category: category of gene-based test; pLOF means putative loss of function.
pos_min: starting position of the region tested, hg38.
pos_max: ending position of the region tested, hg38.
# variants: number of variants tested in the aggregate test.
cMAC: cumulative minor allele count.
STAAR-O P-value: P-values of aggregate tests in 3 cases.
unconditional: P-value of unconditional analysis.
conditional: P-value of conditional analysis conditioning on (1) variants reported on previous literature (Table S6), (2) lead signals from our conditional single variant association analysis.
cond2round: P-value of second round of conditional analysis: conditional list for second round conditional analysis consists of 2 parts: (1) conditional list for the first round conditional analysis; (2) additionally, variants included in the aggregate test which had nominally significant individual variant P-values (P < 1.0 × 10−6) (Tables S10A and S11A). Note that not all gene sets have such remaining significant variants, so we do not further perform the second round conditional analysis in these cases, and leave the column blank.
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