Table 1 Examples of RSS-NET highlighted genes that were not reported in GWAS of the same data but were implicated in later GWAS with increased sample sizes (genome-wide significance threshold: single-SNP association P < 5 × 10−8).
From: Modeling regulatory network topology improves genome-wide analyses of complex human traits
Trait | Gene (Role) | \({P}_{1}^{{\mathsf{base}}}\) | \({P}_{1}^{{\mathsf{near}}}\) | \({P}_{1}^{{\mathsf{bma}}}\) | \({P}_{1}^{{\mathsf{net}}}\) (Network, BF) | Mouse trait | Therapeutic and clinical evidence |
|---|---|---|---|---|---|---|---|
BMI | PAX2 (TF) | 0.78 | 0.80 | 0.94 | 0.94 (Pancreas, 2.07 × 1013) | Eye, Renal | Ocular and renal anomalies |
FLT3 (TG) | 0.61 | 0.70 | 0.85 | 0.85 (Cerebellum, 8.70 × 1011) | Growth, Immune | Acute myeloid leukemia | |
WAIST | LAMB1 (TG) | 0.97 | 0.97 | 0.98 | 0.98 (Esophagus, 6.78 × 10239) | Neuron, NS | Lissencephaly-5 |
BC | KCTD1 (TG) | 0.89 | 0.93 | 0.98 | 0.98 (Heart, 8.08 × 107) | CS | Scalp-ear-nipple syndrome |
CASP8 (TG) | 0.71 | 0.72 | 0.94 | 0.94 (Aorta, 8.27 × 108) | Growth, Immune | Hepatoma, Glionitrin A* | |
RA | AIRE (TF) | 0.54 | 0.61 | 0.84 | 0.84 (B cell, 3.31 × 1057) | Immune | APS1 |
IBD | LPP (TG) | 0.98 | 0.94 | 0.99 | 0.99 (Monocyte, 6.28 × 1031) | Cellular | Acute myeloid leukemia |
FOXP1 (TF) | 0.84 | 0.78 | 0.95 | 0.95 (NK cell, 5.07 × 1035) | Immune, Neuron | Language impairment | |
CCND3 (TG) | 0.81 | 0.89 | 0.95 | 0.95 (NK cell, 5.07 × 1035) | Immune | ||
HDL | ALOX5 (TG) | 0.97 | 0.97 | 0.99 | 0.99 (Monocyte, 4.75 × 1015) | Immune, Metab. | Atherosclerosis |
GPAM (TG) | 0.92 | 0.95 | 0.98 | 0.98 (Liver, 2.81 × 1021) | Liver, Metab. | ||
NR0B2 (TG) | 0.84 | 0.93 | 0.98 | 0.98 (Liver, 2.81 × 1021) | Growth, Metab. | Early-onset obesity | |
LDL | CERS2 (TG) | 0.99 | 0.99 | 1.00 | 1.00 (NK cell, 5.18 × 1030) | Liver, Metab. | |
ABCA1 (TG) | 0.98 | 0.98 | 0.99 | 0.99 (Liver, 7.66 × 1027) | Liver, Metab. | Tangier disease, Probucol* | |
ABCB11 (TG) | 0.68 | 0.72 | 0.88 | 0.88 (Liver, 7.66 × 1027) | Liver, Metab. | Cholestasis | |
DLG4 (TG) | 0.69 | 0.59 | 0.85 | 0.85 (NK cell, 5.18 × 1030) | Metab., NS | Tat-NR2B9c* | |
SOX17 (TF) | 0.52 | 0.65 | 0.82 | 0.84 (CD8, 5.86 × 1028) | Liver, Metab. | Vesicoureteral reflux-3 | |
CAD | TGFB1 (TG) | 0.92 | 0.99 | 0.99 | 0.99 (Adipose, 1.67 × 1029) | CS, Growth | Camurati-Engelmann disease |
FN1 (TG) | 0.58 | 0.79 | 0.91 | 0.92 (GEJ, 9.78 × 1028) | CS, Metab. | GFND2, SMDCF | |
CDH13 (TG) | 0.31 | 0.55 | 0.77 | 0.82 (Heart, 1.93 × 1028) | CS, Metab. | ||
EDNRA (TG) | 0.57 | 0.79 | 0.80 | 0.82 (Aorta, 1.09 × 1027) | CS, Muscle | Ambrisentan*, Macitentan* | |
AF | SCN5A (TG) | 0.87 | 0.92 | 1.00 | 1.00 (Heart, 6.89 × 1012) | CS, Muscle | Brugada syndrome-1, ATFB10 |
ENPEP (TG) | 0.50 | 0.76 | 0.92 | 0.94 (Uterus, 2.71 × 1011) | QGC-001* | ||
ATXN1 (TG) | 0.45 | 0.62 | 0.90 | 0.90 (Colon, 7.54 × 1014) | Muscle, NS | Spinocerebellar ataxia-1 | |
MYOT (TG) | 0.55 | 0.66 | 0.86 | 0.87 (Muscle, 8.55 × 1014) | Myofibrillar myopathy | ||
SCZ | FOXP1 (TF) | 1.00 | 1.00 | 1.00 | 1.00 (Colon, 1.20 × 10144) | Growth, Neuron | Language impairment |
BCL11A (TG) | 1.00 | 1.00 | 1.00 | 1.00 (Spleen, 1.44 × 10141) | Immune, NS | Dias-Logan syndrome | |
SLC25A12 (TG) | 0.79 | 0.81 | 0.88 | 0.88 (Muscle, 4.99 × 10127) | Neuron, NS | DEE39 | |
NEU | TCF4 (TF) | 0.72 | 0.88 | 0.95 | 0.95 (CD8, 3.66 × 1020) | Immune, NS | Pitt-Hopkins syndrome |
RAPSN (TG) | 0.77 | 0.88 | 0.93 | 0.93 (Muscle, 8.20 × 1017) | Muscle, NS | Congenital myasthenic syndrome-11 | |
MEF2C (TF) | 0.15 | 0.40 | 0.83 | 0.83 (Ileum, 8.56 × 1022) | Growth, Neuron | Mental retardation-20 | |
SNCA (TG) | 0.15 | 0.32 | 0.78 | 0.79 (Putamen, 2.12 × 1019) | Neuron, NS | Parkinsonism, BIIB054* | |
PAX6 (TF) | 0.10 | 0.22 | 0.62 | 0.64 (Putamen, 2.12 × 1019) | NS, Vision | Optic nerve hypoplasia | |
PCLO (TG) | 0.06 | 0.17 | 0.63 | 0.63 (Ileum, 8.56 × 1022) | Growth, NS | Pontocerebellar hypoplasia-3 |
