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.