Table 2 Genes reaching new de novo enrichment significance.

From: Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders

Gene

DNM All (denovo-db | SPARK-27K)

CH model

denovolyzeR

Significance (union of two models)

Reported significance

dnLGD

dnMIS

dnMIS30

dnLGD p-value

dnMIS p-value

dnMIS30 p-value

dnALT p-value

dnLGD p-value

dnMIS p-value

dnALT p-value

FDR

FWER

Coe253

ASC102

DDD299

New FDR significance

UIMC1

0 (0|0)

6 (4|2)

0 (0|0)

1

1.67E−02

1

2.94E−02

1

5.00E−05

2.01E−04

dnMIS dnALT

–

No

No

No

SMARCC2

4 (2|2)

2 (2|0)

0 (0|0)

6.53E−05

4.44E−01

1

8.20E−03

5.17E−05

3.76E−01

4.49E−03

dnLGD

–

No

Yes

No

NRXN1

1 (1|0)

7 (5|2)

1 (1|0)

2.13E−01

4.70E−03

2.06E−01

2.30E−03

1.57E−01

1.54E−03

4.87E−04

dnALT

–

No

Yes

No

HNRNPK

2 (2|0)

2 (1|1)

2 (1|1)

1.16E−03

3.89E−02

2.30E−04

5.00E−04

6.27E−03

9.96E−02

4.38E−03

dnALT

–

No

No

Yes

GABRG2

1 (0|1)

4 (3|1)

3 (3|0)

2.41E−01

1.52E−01

1.29E−03

8.69E−02

1.22E−01

1.47E−03

4.16E−04

dnALT

–

No

No

No

New FWER significance

ANK2

9 (6|3)

5 (5|0)

1 (1|0)

1.13E−05

9.97E−01

6.88E−01

6.08E−01

6.09E−09

3.03E−01

1.22E−04

dnLGD dnALT

dnLGD

Yes

Yes

No

TBR1

4 (3|1)

3 (2|1)

1 (0|1)

1.93E−07

9.30E−03

2.60E−02

6.81E−07

2.01E−06

6.88E−02

9.41E−05

dnLGD dnALT

dnLGD

Yes

Yes

No

PHF12

4 (3|1)

1 (1|0)

0 (0|0)

1.06E−07

3.02E−01

1

6.08E−05

4.00E−06

6.83E−01

9.15E−03

dnLGD dnALT

dnLGD

Yes

Yes

No

TCF7L2

4 (3|1)

5 (3|2)

3 (3|0)

7.36E−06

2.30E−03

3.70E−04

1.26E−06

1.56E−05

9.05E−04

3.47E−07

dnLGD dnALT

dnALT

Yes

Yes

Yes

SETD2

6 (5|1)

2 (2|0)

1 (1|0)

4.39E−06

8.43E−01

2.56E−01

3.59E−02

3.30E−07

6.63E−01

4.55E−03

dnLGD

dnLGD

Yes

No

Yes

CASZ1

6 (4|2)

2 (0|2)

1 (0|1)

8.43E−07

8.17E−01

2.17E−01

2.35E−02

1.16E−09

7.09E−01

5.10E−03

dnLGD

dnLGD

Yes

No

No

NSD2

5 (4|1)

1 (1|0)

1 (1|0)

4.57E−07

7.20E−01

1.35E−01

3.40E−03

1.19E−07

7.82E−01

6.60E−03

dnLGD

dnLGD

Yes

No

Yes

  1. Five genes newly reached FDR significance and seven genes reached FWER significance in the de novo enrichment analysis, compared to Coe et al.25, using the same methods (CH model and denovolyzeR) with DNMs in 17,426 NDD trios combined from denovo-db (v1.5) and SPARK-27K. The FDR significance threshold qdnEnrich < 0.05 was corrected by the Benjamini–Hochberg method for genes in each method (18,946 genes in CH model and 19,618 genes in denovolyzeR); the FWER significance threshold pdnEnrich < 3.64E−07 was corrected by the Bonferroni method for 19,618 genes and seven tests (dnLGD, dnMIS, dnMIS30, and dnALT variants in CH model, and dnLGD, dnMIS, and dnALT variants in denovolyzeR). Coe253 indicates whether the gene is in the 253 genes reported significant (FDR 5%) in Coe et al.25; ASC102 indicates whether the gene is in the 102 genes reported as significant (FDR 10%) in Satterstrom et al.8; and DDD299 indicates whether the gene is in the 299 genes reported as significant in Kaplanis et al.31. Note different methods and significant threshold were applied in those three studies. See Supplementary Data 10 for underlying data.
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