Table 3.
The top results from gene-based analysis across traits in HyperGEN N=1,934 (the smallest p-value for each gene is shown in bold)
| Left ventricular traits |
Gene name |
Gene-based association p-values | MAF cumulative (Total # of carriers) |
Top single-variant signal | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| MAF < 1% | MAF < 5% | SNP | MAF | p-value | |||||||||
| Burden | MB | SKAT | VT | Burden | MB | SKAT | VT | ||||||
| E/A ratio | KCNH4 | 8.7*10−8 (++) | 8.7*10−8 (++) | 5.2*10−6 (++) | 8.7*10−8 (++) | 8.7*10−8 (++) | 8.7*10−8 (++) | 5.2*10−6 (++) | 8.7*10−8 (++) | 1.6*10−3 (6) | rs139161684 | 8.1*10−4 | 2.0*10−10 |
| LAD | ENDOG | 0.003 (++) | 1.4*10−7 (++) | 0.01 (++) | N/A | 0.003 (++) | 1.4*10−7 (++) | 0.01 (++) | N/A | 2.4*10−3 (9) | rs186499200 | 2.6*10−4 | 2.2*10−11 |
| LVIDD | RAMP1 | 3.4*10−5 (+++) | 2.6*10−7 (+++) | 0.005 (+++) | 2.2*10−6 (++) | 3.4*10−5 (+++) | 2.6*10−7 (+++) | 0.005 (+++) | 1.9*10−6 (++) | 4.2*10−3 (16) | rs142335491 | 5.3*10−4 | 4.6*10−5 |
| E/A ratio | PHKB | 5.7*10−5 (+++++++++−) | 8.4*10−6 (+++++++++−) | 0.008 (+++++++++−) | N/A | 4.9*10−5 (++++++++++−) | 2.1*10−6 (++++++++++−) | 0.02 (++++++++++−) | N/A | 0.04 (142) | rs117218785 | 5.4*10−4 | 5.8*10−5 |
| LAD | GPR55 | N/A | N/A | N/A | N/A | 0.14 (++) | 3.2*10−5 (++) | 0.08 (++) | N/A | 0.02 (93) | rs141404889 | 7.9*10−4 | 2.1*10−7 |
The models were adjusted for age, gender, center, body mass index and first 10 principal components. Direction of SNPs contributing gene-based analysis inside parentheses. Plus means increase, minus means decrease compared to common alleles (additive model). E/A ratio, the ratio of left ventricular transmitral early velocity to late/atrial velocity. LAD, left atrial dimension. LVIDD, left ventricular internal dimension-diastole. E/A ratio and LVIDD were natural log-transformed. LAD was square-rooted. MB, the Madsen-Browning weighted burden test. SKAT, the sequence kernel association test. VT, the variable frequency threshold test. MAF, minor allele frequency. MAF, cumulative and total number of carriers for the most significant test.