Table 1 |. Gene-centric noncoding analysis results of both unconditional analysis and analysis conditional on known common and low-frequency variants.
21,015 discovery samples and 9,123 replication samples from the NHLBI Trans-Omics for Precision Medicine (TOPMed) program are considered in the analysis. Results for the conditionally significant genes (unconditional STAAR-O P < 3.57 × 10−7 and conditional STAAR-O P < 1.16 × 10−3 for 7 different noncoding masks across protein-coding genes; unconditional STAAR-O P < 2.50 × 10−6 and conditional STAAR-O P < 1.16 × 10−3 for ncRNA genes) using discovery samples are presented in the table. The unconditional significant thresholds for both protein-coding genes of 7 different noncoding masks and ncRNA genes were defined by the multiple comparisons using the Bonferroni correction, that is, 0.05/(20,000 × 7) = 3.57 × 10−7 and 0.05/20,000 = 2.50 × 10−6. STAAR-O is a two-sided test. Chr (Chromosome); Category (Functional category); #SNV (Number of rare variants (MAF < 1%) of the particular functional category in the gene); STAAR-O (STAAR-O P value); HDL-C (High-density lipoprotein cholesterol); LDL-C (Low-density lipoprotein cholesterol); TG (Triglycerides); TC (Total cholesterol); Variants Adjusted (Adjusted variants in conditional analysis); n/a, no variant adjusted in the conditional analysis.
| Trait | Gene | Chr | Category | Discovery |
Replication |
Variants Adjusted | ||||
|---|---|---|---|---|---|---|---|---|---|---|
| #SNV | STAAR-O (Unconditional) | STAAR-O (Conditional) | #SNV | STAAR-O (Unconditional) | STAAR-O (Conditional) | |||||
| HDL-C | APOA1 | 11 | enhancer_DHS | 1862 | 2.19E-07 | 7.67E-07 | 1005 | 1.50E-03 | 3.17E-03 | rs964184, rs12269901 |
|
| ||||||||||
| LDL-C | LDLR | 19 | upstream | 68 | 2.35E-17 | 4.24E-04 | 27 | 5.58E-01 | 6.31E-01 | rs12151108, rs688, rs6511720 |
| LDLR | 19 | promoter_CAGE | 131 | 1.88E-17 | 3.37E-04 | 56 | 2.51E-02 | 9.50E-02 | rs12151108, rs688, rs6511720 | |
| APOE | 19 | promoter_CAGE | 91 | 1.45E-11 | 4.88E-12 | 35 | 1.86E-01 | 4.36E-02 | rs7412, rs429358, rs35136575 | |
| LDLR | 19 | promoter_DHS | 257 | 4.03E-17 | 7.21E-04 | 113 | 5.74E-02 | 2.27E-01 | rs12151108, rs688, rs6511720 | |
| APOE | 19 | promoter_DHS | 162 | 9.81E-11 | 3.41E-12 | 64 | 7.45E-02 | 3.42E-02 | rs7412, rs429358, rs35136575 | |
| LDLR | 19 | enhancer_CAGE | 150 | 2.82E-17 | 5.01E-04 | 71 | 1.20E-02 | 4.05E-02 | rs12151108, rs688, rs6511720 | |
| APOE | 19 | enhancer_DHS | 239 | 9.84E-11 | 2.03E-11 | 112 | 2.55E-01 | 1.34E-01 | rs7412, rs429358, rs35136575 | |
| CTC-527H23.4 | 16 | ncRNA | 32 | 1.15E-06 | 1.15E-06 | 17 | 9.12E-01 | 9.12E-01 | n/a | |
|
| ||||||||||
| TG | APOE | 19 | promoter_CAGE | 92 | 4.45E-12 | 7.48E-06 | 36 | 9.45E-06 | 3.53E-05 | rs12721054, rs5112, rs429358 |
| APOA5 | 11 | promoter_DHS | 175 | 2.39E-08 | 3.47E-05 | 84 | 1.19E-04 | 8.78E-03 | rs964184, rs9804646, rs3135506, rs2266788 | |
| APOE | 19 | promoter_DHS | 163 | 1.80E-11 | 9.56E-06 | 65 | 2.96E-06 | 1.13E-05 | rs12721054, rs5112, rs429358 | |
| COL18A1 | 21 | enhancer_CAGE | 256 | 1.92E-07 | 1.92E-07 | 147 | 4.57E-02 | 4.57E-02 | n/a | |
| APOE | 19 | enhancer_DHS | 241 | 2.02E-11 | 8.44E-05 | 116 | 1.12E-05 | 4.15E-05 | rs12721054, rs5112, rs429358 | |