Table 1.
Results for meta-analysis of gene-level rare variant association test. Associations that attain exome-wide significance (p < 3.1×10-6) are displayed. Five gene-level association tests were used to analyze the data: simple burden tests with 1% or 5% cutoff (Burden-1 and Burden-5), SKAT tests with 1% or 5% cutoff (SKAT-1 and SKAT-5) and variable threshold (VT) tests that analyze variants with MAF<5%. Significant p-values for each test are displayed in bold font. For the associations that are significant, estimates of average genetic effect are also shown. The loci where one or more gene-based association signal exceeds the top single variant association signal are labeled with an asterisk.
| Gene | Gene Positiona | Burden-1 | Burden-5 | SKAT-1 | SKAT-5 | VT | MAF Cutoff | Direction of Single Variant Association Statisticsb | Estimates of Genetic Average Effect (s.d units) for Rare Variants under Different MAF Thresholds | ||
|---|---|---|---|---|---|---|---|---|---|---|---|
|
| |||||||||||
| 0.01 | 0.05 | VT | |||||||||
| HDL | |||||||||||
| LIPC* | chr15:58.7Mb | 1.4×10-12 | 3.5×10-7 | 1.8×10-9 | 1.4×10-2 | 4.5×10-12 | 3.7×10-3 | -++++--+- | 0.5 | 0.1 | 0.5 |
| LPL* | chr8:19.8Mb | 9.7×10-1 | 2.5×10-24 | 3.5×10-1 | 5.0×10-13 | 1.5×10-23 | 2.5×10-2 | (-)-(-)+-++ | - | -0.3 | -0.3 |
| ANGPTL4* | chr19:8.4Mb | 2.2×10-2 | 2.9×10-19 | 2.2×10-2 | 3.0×10-19 | 1.8×10-18 | 2.6×10-2 | (+)--++-+++ | - | 0.3 | 0.3 |
| LIPG* | chr18:47.1Mb | 2.2×10-5 | 6.4×10-19 | 2.1×10-5 | 2.9×10-9 | 4.4×10-18 | 1.3×10-2 | -++----(+)+ | - | 0.4 | 0.4 |
| HNF4A | chr20:43.0Mb | 7.5×10-1 | 2.8×10-7 | 6.8×10-1 | 2.5×10-7 | 1.5×10-6 | 4.1×10-2 | (-)--+-+ | - | -0.1 | -0.1 |
| CD300LG | chr17:41.9Mb | 4.9×10-1 | 8.5×10-7 | 5.2×10-1 | 1.0×10-5 | 3.1×10-6 | 3.3×10-2 | (-)+-(+) | - | -0.1 | - |
|
| |||||||||||
| LDL | |||||||||||
| PCSK9* | chr1:55.5Mb | 1.8×10-2 | 7.4×10-19 | 8.1×10-2 | 5.5×10-17 | 2.0×10-28 | 1.3×10-2 | (-)--(-)--+-++- | - | -0.3 | -0.5 |
| BCAM | chr19:45.3Mb | 1.7×10-1 | 1.6×10-18 | 1.5×10-1 | 3.0×10-5 | 2.6×10-17 | 3.6×10-2 | (-)+++(-)+-+++---+(-)+--+--++ | - | -0.1 | -0.1 |
| CBLC | chr19:45.3Mb | 9.4×10-1 | 2.0×10-15 | 4.4×10-1 | 1.5×10-4 | 1.0×10-14 | 4.4×10-2 | -(-)--+-(-)(+) | - | -0.1 | -0.1 |
| PVR | chr19:45.2Mb | 6.1×10-2 | 3.0×10-10 | 4.8×10-2 | 6.3×10-2 | 1.1×10-9 | 4.9×10-2 | (-)++--+ | - | -0.1 | -0.1 |
| LDLR* | chr19:11.2Mb | 1.8×10-3 | 4.7×10-5 | 3.8×10-2 | 2.5×10-1 | 2.4×10-7 | 5.2×10-4 | +++++++++-++++--+ | - | - | 0.8 |
|
| |||||||||||
| TG | |||||||||||
| ANGPTL4* | chr19:8.4Mb | 2.6×10-2 | 1.2×10-24 | 3.7×10-2 | 3.9×10-25 | 7.1×10-24 | 2.6×10-2 | (-)+---+--- | - | -0.3 | -0.2 |
| LPL* | chr8:19.8Mb | 6.8×10-1 | 7.7×10-20 | 2.6×10-1 | 1.8×10-11 | 4.6×10-19 | 2.5×10-2 | (+)+(+)--+- | - | 0.2 | 0.2 |
Gene position is defined based upon hg19, GRCh37 Genome Reference Consortium Human Reference 37
Direction of single site statistics for variants with MAF<5%. Variants within parenthesis have frequency >1%.
The loci with one or more gene-level association signal exceeding the top single variant signal.