Table 3 Multivariable regression analysis of polygenic associations between ADHD and literacy-related and language-related abilities (raw estimates)

From: Disentangling polygenic associations between attention-deficit/hyperactivity disorder, educational attainment, literacy and language

LRAs

ADHD-specific effects independent of EA (βADHD)

EA genetic effects of ADHD-associated variantsa (βEA)

Conservative instruments (Pthr < 5 × 10-8)

Subthreshold instruments (Pthr < 0.0015)

Conservative instruments (Pthr < 5 × 10-8)

Subthreshold instruments (Pthr < 0.0015)

β (SE)

P

P het

β (SE)

P

P het

β (SE)

P

P het

β (SE)

P

P het

Reading a/c 7 (WORD)

–0.18 (0.13)

0.20

—

–0.03 (0.01)

1.4 × 10−5

—

−0.09 (1.19)

0.94

—

−0.63(0.10)

1.2 × 10−9

—

Reading a 9 (NBO)

−0.28 (0.09)

0.01

—

−0.03 (0.01)

2.1 × 10−4

—

1.33 (0.84)

0.14

—

−0.46 (0.10)

6.3 × 10−6

—

Reading s 9 (NARA II)

−0.29 (0.13)

0.04

—

−0.03 (0.01)

3.0 × 10−5

—

1.55 (1.16)

0.21

—

−0.51 (0.11)

2.5 × 10−6

—

Reading a 9 (NARA II)

−0.34 (0.12)

0.01

—

−0.03 (0.01)

3.8 × 10−4

—

1.57 (1.11)

0.18

—

−0.64 (0.11)

4.1 × 10−9

—

Reading s 13 (TOWRE)

−0.36 (0.15)

0.03

—

−0.04 (0.01)

2.7 × 10−5

—

2.06 (1.35)

0.15

—

−0.46 (0.12)

1.8 × 10−4

—

NW reading a 9 (NBO)

−0.37 (0.09)

0.002

—

−0.03 (0.01)

2.4 × 10−4

—

1.54 (0.85)

0.09

—

−0.46 (0.10)

6.1 × 10−6

—

NW reading s 13 (TOWRE)

−0.21 (0.17)

0.25

—

−0.03 (0.01)

2.4 × 10−4

—

1.43 (1.58)

0.38

—

−0.45 (0.12)

1.9 × 10-4

—

Spelling a 7 (NB)

−0.05 (0.12)

0.72

—

−0.05 (0.01)

1.4 × 10−5

—

-1.12 (1.13)

0.34

—

−0.63 (0.10)

1.2 × 10−9

—

Spelling a 9 (NB)

−0.23 (0.08)

0.01

—

−0.04 (0.01)

8.7 × 10−7

—

1.43 (0.72)

0.38

—

−0.45 (0.10)

1.3 × 10−5

—

PhonAware 7 (AAT)

−0.22 (0.15)

0.16

—

−0.02 (0.01)

0.002

—

−0.31 (1.33)

0.82

—

−0.67 (0.10)

< 1 × 10−10

—

Listening c 8 (WOLD)

−0.03 (0.08)

0.75

—

−0.02 (0.01)

0.02

—

−1.47 (0.70)

0.06

—

−0.55 (0.11)

4.5 × 10−7

—

Non-word repetition 8 (CNRep)

−0.14 (0.14)

0.34

—

−0.02 (0.01)

0.01

—

−0.16 (1.30)

0.90

—

−0.47 (0.11)

1.5 × 10−5

—

VIQ 8 (WISC-III)

−0.23 (0.15)

0.16

—

−0.03 (0.01)

5.0 × 10−5

—

−0.36 (1.37)

0.80

—

−0.71 (0.11)

< 1 × 10−10

—

Pooled reading

−0.35 (0.09)

9.2 × 10−5

0.19

−0.03 (0.01)

1.4 × 10−6

0.79

1.67 (0.78)

0.03

0.31

−0.50 (0.09)

4.9 × 10−8

0.09

Pooled spelling

−0.18 (0.11)

0.10

0.03

−0.04 (0.01)

1.1 × 10−8

0.28

0.40 (1.25)

0.75

0.001

−0.42 (0.10)

1.3 × 10−5

0.39

Pooled LRAs

−0.18 (0.07)

0.01

0.005

−0.03 (0.01)

1.9 × 10−6

0.05

0.29 (0.69)

0.67

0.001

−0.49 (0.08)

< 1 × 10−10

0.004

  1. Note: Sets of conservative (P < 5 × 10−8) and subthreshold (P < 0.0015) ADHD instruments were extracted from ADHD (PGC + iPSYCH), EA (SSGAC) and LRAs (ALSPAC) GWAS summary statistics. ADHD-specific effects independent of EA (βADHD) and ADHD effects shared with EA (βEA) on LRAs were estimated with MVRs (Fig. 2b). ADHD effects shared with EA were assessed through EA genetic effect estimates of ADHD-associated variants and presented with respect to missing school years. βADHD quantifies the change in LRA Z-score per log odds increase in ADHD liability. βEA quantifies the change in LRA Z-score per missing year of schooling. Pooled estimates for reading, spelling and global LRAs (Table 1) were obtained through random-effects meta-regression. Evidence for effect heterogeneity (Phet) was monitored through Cochran’s Q-test. To compare effect sizes of βADHD and βEA, MVR was carried out using standardised genetic effect estimates for which results are provided in Fig. 2c.
  2. LRAs literacy-related and language-related abilities, ADHD Attention-Deficit/Hyperactivity Disorder, EA educational attainment, PthrP-value threshold, Phet heterogeneity P-value, a accuracy, c comprehension, s speed, WORD Wechsler Objective Reading Dimension, NBO Nunes, Bryant and Olson (ALSPAC specific instrument), NARA II The Neale Analysis of Reading Ability-Second Revised British Edition, TOWRE Test Of Word Reading Efficiency, NW non-word, NB Nunes and Bryant (ALSPAC specific instrument), PhonAware phonemic awareness, AAT Auditory Analysis Test, WOLD Wechsler Objective Language Dimensions, CNRep Children’s Test of Nonword Repetition, VIQ verbal intelligence quotient, WISC-III Wechsler Intelligence Scale for Children III, MVR Multivariable regression
  3. aADHD genetic effects shared with EA as assessed through EA genetic effect estimates of ADHD-associated variants
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