Table 1 Candidate list of genes that display abnormal DNA-methylation levels, and harbor risk-SNPs.

From: Susceptible genes and disease mechanisms identified in frontotemporal dementia and frontotemporal dementia with Amyotrophic Lateral Sclerosis by DNA-methylation and GWAS

Genesymbol

Chr

Strand

GWAS SNPs

DNA-methylation probes

Network

Pathway

Validated by gene-expression

Id

P

Location

CADD score

min(P) for gene

Id

P BH

Location

Tstat

Gene-degree

Overlap

DLG1

chr3

−

rs74674649

6.01E-04

exonic

28.2

6.01E-04

cg12594803

0.0288

.

–7.04

6

Yes

Yes

KIAA1147

chr7

−

rs201876806

9.13E-04

exonic

23.4

9.13E-04

cg24662653

2.90E-03

Island

–6.51

2

 

Yes

GGA1

chr22

+

rs143909159

2.91E-03

exonic

34

2.91E-03

cg21268578

0.028

.

–7.16

21

  

IGHMBP2

chr11

+

rs201692151

4.00E-03

exonic

22.8

4.00E-03

cg26065952

0.0231

N_Shore

–5.7

31

 

Yes

ASPM

chr1

−

rs150125249

5.78E-03

exonic

34

5.78E-03

cg11336294

0.0273

.

–5.59

.

Yes

 

PRSS36

chr16

−

rs145749002

6.04E-03

exonic

33

6.04E-03

cg14301190

4.90E-03

Island

–6.68

1

  

CNKSR1

chr1

+

rs144396219

8.32E-03

exonic

27.7

8.32E-03

cg09890400

0.0196

.

–8.83

11

 

Yes

UBTD2

chr5

−

rs17074452

9.54E-03

exonic

18.33

9.54E-03

ch.5.3268483F

4.90E-03

.

–5.84

12

 

Yes

GGA1

chr22

+

rs138525343

9.76E-03

exonic

26.6

2.91E-03

cg21268578

0.028

.

–7.16

21

  

IGHMBP2

chr11

+

rs145226920

0.01001

exonic

35

4.00E-03

cg26065952

0.0231

N_Shore

–5.7

31

  

FAH

chr15

+

rs144234072

0.01066

exonic

27.3

0.01066

cg06856840

0.0165

.

–6.95

2

Yes

 

NEDD9

chr6

−

rs34044517

0.01629

exonic

23.6

5.85E-03

cg05917225

9.20E-03

.

–5.79

2

  

BPHL

chr6

+

rs2231365

0.01671

splicing

24.1

0.01671

cg22799902

6.20E-03

Island

–6.43

2

  

ACTN3

chr11

+

rs201576110

0.02133

exonic

32

0.02133

cg25117505

6.39E-06

Island

–8.39

.

  

WDR66

chr12

+

rs77422261

0.02336

exonic

29.7

0.02336

cg21016266

0.0133

Island

–4.89

3

  

IQSEC. 1

chr3

−

rs144790333

0.02763

exonic

23

0.02763

cg02559896

6.70E-03

Island

–5.14

16

Yes

 

DLG1

chr3

−

rs141544348

0.03024

exonic

35

6.01E-04

cg12594803

0.0288

.

–7.04

6

  

DUOX1

chr15

+

rs143304688

0.03047

exonic

44

0.03047

cg10496082

2.00E-04

Island

–6.61

4

Yes

 

PCDHA3

chr5

+

rs146951816

0.0354

exonic

15.16

0.0354

cg02357321

0.0335

N_Shore

–6.43

.

  

C6orf70

chr6

+

rs140632188

0.04056

exonic

23

0.04056

cg22807378

0.0121

Island

–7.15

1

  

CLRN2

chr4

+

rs201124485

0.04711

exonic

20.6

0.04711

cg16760587

1.10E-03

S_Shelf

–6.06

.

  

COL15A1

chr9

+

rs199906142

3.62E-03

exonic

23.1

3.62E-03

cg18115656

0.0366

Island

5.37

0

Yes

 

TNRC18

chr7

−

rs112785272

6.27E-03

exonic

19.2

6.27E-03

cg10546562

0.0101

N_Shore

5.91

28

Yes

 

SLC26A7

chr8

+

rs200788056

9.04E-03

exonic

23.3

9.04E-03

cg25481252

2.60E-03

.

7.38

.

  

PCNX

chr14

+

rs200261097

0.01309

exonic

32

0.01309

cg10066683

0.0422

.

5.34

31

Yes

Yes

WDR35

chr2

−

rs148436608

0.02293

exonic

16.34

0.02293

cg13734338

0.028

.

6

0

 

Yes

MEGF6

chr1

−

rs61910697

0.03109

exonic

19.86

0.03109

cg04391135

3.50E-03

Island

6.21

0

  

PRR5-ARHGAP8

chr22

+

rs55849456

0.03933

exonic

24.6

0.03933

cg06647930

0.0442

S_Shelf

4.26

.

 

Yes

PRR5-ARHGAP8

chr22

+

rs16992915

0.04662

exonic

19.38

0.03933

cg06647930

4.42E-02

S_Shelf

4.26

.

 

Yes

ESYT2

chr7

−

rs2305475

0.04728

exonic

23

0.04728

cg19584649

9.36E-05

.

6.66

15

 

Yes

  1. Detection of 26 candidate genes for 30 SNPs for FTD-ALS. Genes are grouped in DNA hypomethylated (DMP T-statistics < 0) and hypermethylated genes (DMP T-statistics > 0) followed by P-value significance of GWAS. Chr: Chromosome. GWAS P: P-value significance for the phenotype association. GWAS CADD score: quantifies the deleteriousness of the SNP in the gene (the higher the worse). GWAS min(P) for gene: Minimum P-value significance for the phenotype association without excluding intronic, and intergenic SNPs. DMP PBY: P-value for the DNA-methylation difference between FTD-ALS vs Control cases after multiple test correction using Benjamini and Hochberg. DMP T-stat: T-statistics. Network Gene-degree: the number of edges the gene contains in the co-expression network (Fig. 4). Pathway overlap: [Yes], if the gene overlaps with any of the pathways derived from DMP or GWAS (Fig. 3A and B). Validated by gene-expression: [Yes], if the gene showed significant differential expression in any of the validation data sets.
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