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 |
0.00 (++) |
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.