Table 2 Examples of RSS-NET highlighted genes that have not reached genome-wide significance in the GWAS Catalog1 at the time of analysis.

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

NEXN (TG)

0.71

0.79

0.89

0.90 (Muscle, 9.31 × 1012)

CS, Muscle

Cardiomyopathy

 

CDX2 (TF)

0.61

0.70

0.83

0.86 (NK cell, 3.95 × 1013)

DS, Growth

 

WAIST

BSCL2 (TG)

0.80

0.68

0.87

0.87 (Esophagus, 6.78 × 10239)

Adipose, Growth

Berardinelli-Seip syndrome

 

FOXP2 (TF)

0.56

0.59

0.73

0.73 (Esophagus, 6.78 × 10239)

Growth, NS

Speech-language disorder-1

BC

ADSL (TG)

0.76

0.80

0.91

0.92 (Aorta, 8.27 × 108)

CS, Eye

Adenylosuccinase deficiency

 

SYNE1 (TG)

0.57

0.63

0.89

0.90 (Esophagus, 6.30 × 107)

Growth, Muscle

AMC3, EDMD4, SCAR8

RA

TAL1 (TF)

0.71

0.79

0.91

0.93 (CD4, 3.02 × 1052)

Immune, Tumor

Acute lymphocytic leukemia

 

FHIT (TG)

0.30

0.60

0.90

0.91 (CD4, 3.02 × 1052)

Immune, Tumor

 
 

FLT3 (TG)

0.33

0.57

0.73

0.73 (B cell, 3.31 × 1057)

Immune, Tumor

Acute myeloid leukemia

IBD

FHIT (TG)

0.63

0.87

0.95

0.95 (CD4, 5.32 × 1033)

Immune, Tumor

 
 

GATA3 (TF)

0.85

0.83

0.94

0.94 (NK cell, 5.07 × 1035)

Immune, Renal

Barakat syndrome

 

RORA (TF)

0.66

0.78

0.87

0.90 (B cell, 1.49 × 1032)

Immune, NS

Intellectual disability

 

NFKB2 (TF)

0.74

0.85

0.84

0.88 (B cell, 1.49 × 1032)

Immune

Immunodeficiency, DIMS-0150*

 

LRBA (TG)

0.42

0.58

0.72

0.72 (NK cell, 5.07 × 1035)

Immune

Immunodeficiency

 

DOCK2 (TG)

0.38

0.53

0.71

0.71 (NK cell, 5.07 × 1035)

Immune

Immunodeficiency

HDL

MT1G (TG)

0.10

0.09

0.98

0.98 (Liver, 2.81 × 1021)

CS, Metab.

 
 

RETSAT (TG)

0.79

0.80

0.95

0.95 (Liver, 2.81 × 1021)

Adipose, Metab.

 
 

ESR1 (TF)

0.77

0.82

0.95

0.95 (Liver, 2.81 × 1021)

CS, Metab.

Myocardial infarction

 

HCAR3 (TG)

0.85

0.85

0.92

0.92 (Monocyte, 4.75 × 1015)

Metab.

ARI-3037MO*

 

TNNC1 (TG)

0.48

0.45

0.78

0.78 (Liver, 2.81 × 1021)

CS, Muscle

Cardiomyopathy, Levosimendan*

LDL

RAF1 (TG)

0.79

0.83

0.90

0.90 (Aorta, 3.71 × 1027)

CS, Immune

Cardiomyopathy, Semapimod*

 

APOA1 (TG)

0.70

0.76

0.90

0.90 (Liver, 7.66 × 1027)

CS, Metab.

Amyloidosis, HDL deficiency

 

ACADVL (TG)

0.69

0.59

0.85

0.85 (NK cell, 5.18 × 1030)

Liver, Metab.

VLCAD deficiency

T2D

ITGB6 (TG)

0.75

0.99

0.99

0.99 (Ileum, 4.52 × 1062)

Immune, Metab.

Amelogenesis imperfecta type IH

HR

TKT (TG)

0.65

0.67

0.92

0.93 (Aorta, 2.43 × 107)

CS, Growth

SDDHD

CAD

OSM (TG)

0.56

0.78

0.86

0.86 (Aorta, 1.09 × 1027)

Immune, Metab.

GSK2330811*

 

TRIB1 (TG)

0.43

0.68

0.85

0.85 (Adipose, 1.67 × 1029)

Adipose, Metab.

 
 

TAB2 (TG)

0.19

0.43

0.61

0.61 (CD8, 1.13 × 1025)

CS

Congenital heart defects

AF

TPMT (TG)

0.88

0.93

0.99

0.99 (Ileum, 4.43 × 1013)

Metab.

Poor metabolism of thiopurines-1

 

RUNX1 (TF)

0.44

0.60

0.88

0.89 (Heart, 2.15 × 1014)

CS, Immune

Acute myeloid leukemia, FPDMM

 

CSF3 (TG)

0.56

0.72

0.88

0.88 (Muscle, 8.55 × 1014)

Blood, Immune

Interleukin-3*

LOAD

CASP2 (TG)

0.99

1.00

1.00

1.00 (CD8, 8.31 × 1026)

Cellular, NS

Caspase-2*

 

TTR (TG)

0.64

0.92

0.94

0.94 (Pancreas, 3.53 × 1020)

Metab.

Amyloidosis, Inotersen*, Patisiran*

SCZ

RORA (TF)

1.00

1.00

1.00

1.00 (Cortex, 5.39 × 10128)

Neuron, NS

Intellectual disability

 

ERBB4 (TG)

1.00

1.00

1.00

1.00 (Putamen, 7.22 × 10116)

Neuron, NS

Amyotrophic lateral sclerosis-19

 

NFIB (TF)

0.97

0.97

0.98

0.98 (Cortex, 5.39 × 10128)

NS

MACID

 

GRIK2 (TG)

0.90

0.94

0.97

0.97 (Cerebellum, 3.15 × 10129)

Neuron, NS

Mental retardation

 

SYT1 (TG)

0.84

0.89

0.93

0.93 (Cerebellum, 3.15 × 10129)

Neuron, NS

Baker-Gordon syndrome

 

ESR1 (TF)

0.80

0.84

0.93

0.93 (Colon, 1.07 × 10141)

Neuron, NS

Migraine

 

NTRK2 (TG)

0.78

0.84

0.91

0.91 (Cerebellum, 3.15 × 10129)

Neuron, NS

DEE58

 

LRRK2 (TG)

0.73

0.78

0.86

0.86 (Monocyte, 5.85 × 10131)

Neuron, NS

Parkinsonism, DNL151*, DNL201*

 

C9orf72 (TG)

0.74

0.78

0.83

0.83 (Spleen, 1.44 × 10141)

Neuron, NS

FTDALS1

 

SNCA (TG)

0.60

0.66

0.74

0.74 (Cerebellum, 3.15 × 10129)

Neuron, NS

Parkinsonism, BIIB054*

NEU

LMBRD1 (TG)

0.42

0.66

0.94

0.94 (Ileum, 8.56 × 1022)

Metab.

MAHCF

 

PRKCQ (TG)

0.36

0.56

0.90

0.91 (Spleen, 2.13 × 1019)

Immune, NS

 
 

ATP1A2 (TG)

0.33

0.39

0.76

0.78 (Putamen, 2.12 × 1019)

Neuron, NS

AHC1, FHM2

  1. AMC3: myogenic-type arthrogryposis multiplex congenita-3. EDMD4: Emery-Dreifuss muscular dystrophy-4. SCAR8: autosomal recessive spinocerebellar ataxia-8. VLCAD: very long-chain acyl-CoA dehydrogenase. SDDHD: short stature, developmental delay, and congenital heart defects. FPDMM: familial platelet disorder with associated myeloid malignancy. MACID: acquired macrocephaly with impaired intellectual development. FTDALS1: frontotemporal dementia and/or amyotrophic lateral sclerosis. MAHCF: methylmalonic aciduria and homocystinuria of the cblF type. AHC1: alternating hemiplegia of childhood-1. FHM2: familial hemiplegic migraine-2. The remaining abbreviations are the same as in Table 1.
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