Dyslexia Polygenic Scores Show Heightened Prediction of Verbal Working Memory and Arithmetic

Figures & data

Table 1. The total sample size, number of MZ twins (MZ), Dizygotic Twins (DZ) and non-twin siblings. Percentage of females for each group are reported in brackets.

	Total	MZ	DZ	Non-twin siblings	Study
IQ Subtests
Information	1223 (F 54.7%)	186 (F 55.4%)	855 (F 52.6%)	182 (F 63.7%)	MAPS
Arithmetic	1223 (F 54.7%)	186 (F 55.4%)	855 (F 52.6%)	182 (F 63.7%)	MAPS
Vocabulary	1222 (F 54.7%)	186 (F 55.4%)	854 (F 52.7%)	182 (F 63.7%)	MAPS
Spatial	1223 (F 54.7%)	186 (F 55.4%)	855 (F 52.6%)	182 (F 63.7%)	MAPS
Object Assembly	1221 (F 54.7%)	186 (F 55.4%)	854 (F 52.7%)	181 (F 63.5%)	MAPS
Digit Symbol	1190 (F 54.7%)	183 (F 56.3%)	825 (F 52.4%)	182 (F 63.7%)	MAPS
Digits Forward	1542 (F 52.8%)	220 (F 54.5%)	955 (F 50.7%)	367 (F 57.2%)	BATS
Working Memory
Digits Backward	1542 (F 52.8%)	220 (F 54.5%)	955 (F 50.7%)	367 (F 57.2%)	BATS
Letter-Number Sequencing	1542 (F 52.8%)	220 (F 54.5%)	955 (F 50.7%)	367 (F 57.2%)	BATS
Elementary Cognitive Tasks
Inspection Time	842 (F 55.3%)	126 (F 57.1%)	598 (F 53.3%)	118 (F 63.6%)	MAPS
2-CRT	1085 (F 54.7%)	166 (F 56.6%)	765 (F 52.9%)	154 (F 61%)	MAPS
4-CRT	1086 (F 54.7%)	166 (F 56.6%)	766 (F 53%)	154 (F 61%)	MAPS
8-CRT	907 (F 54.9%)	139 (F 59%)	638 (F 52.7%)	130 (F 61.5%)	MAPS
Visuo-Spatial Working Memory
Accuracy	734 (F 54.8%)	114 (F 60.5%)	521 (F 52.4%)	99 (F 60.6%)	MAPS
Creative Writing
Create and Present	959 (F 58.1%)	138 (F 59.4%)	671 (F 56%)	150 (F 66%)	MAPS

MAPS: Memory, Attention and Problem Solving; BATS: Brisbane Adolescent Twin Study.

Figure 1. Variance explained in the cognitive test scores by the dyslexia polygenic and reading difficulties phenotypic scores

Table 2. Estimates with the associated 95% CI, standard error, the student t and the associated p-value for the fixed effects of the models containing the proxy for dyslexia to the left and the dyslexia PGS to the right.

Dyslexia phenotype estimate		Std.Error	t	P	Dyslexia PGS estimate		Std.error	t	P
IQ subtests
Information	−0.25 [−0.32, −0.19]	0.108	−7.238	0.000 ***	Information	−0.12 [−0.19, −0.05]	0.030	−3.176	0.003 **
Arithmetic	−0.25 [−0.31, −0.19]	0.111	−7.679	0.000 ***	Arithmetic	−0.20 [−0.27, −0.13]	0.030	−5.839	0.000 **
Vocabulary	−0.22 [−0.29, −0.15]	0.120	−6.418	0.000 ***	Vocabulary	−0.11 [−0.18, −0.04]	0.030	−3.063	0.004 **
Spatial	−0.20 [−0.27, −0.14]	0.112	−6.213	0.000 ***	Spatial	−0.11 [−0.18, −0.04]	0.030	−3.165	0.003 **
Object Assembly	−0.10 [−0.17, −0.04]	0.113	−3.011	0.003 **	Object Assembly	−0.03 [−0.10, 0.04]	0.031	−0.818	0.619
Digit Symbol	−0.15 [−0.21, −0.08]	0.114	−4.422	0.000 ***	Digit Symbol	−0.15 [−0.22, −0.08]	0.030	−4.383	0.000 ***
Digits Forward	−0.13 [−0.19, −0.07]	0.092	−4.595	0.000 ***	Digits Forward	−0.11 [−0.17, −0.05]	0.027	−3.807	0.001 ***
Working Memory
Digits Backward	−0.07 [−0.13, −0.02]	0.094	−2.723	0.007 **	Digits Backward	−0.09 [−0.15, −0.04]	0.001	−3.254	0.003 **
Letter-Number Sequencing	−0.10 [−0.16, −0.05]	0.093	−3.721	0.000 ***	Letter-Number Sequencing	−0.15 [−0.20, −0.09]	0.027	−5.140	0.000 ***
Elementary Cognitive Tasks
Inspection Time	0.17 [0.10, 0.24]	0.150	4.779	0.000 ***	Inspection Time	0.02 [−0.05, 0.10]	0.036	0.622	0.667
2-Choice RT	0.16 [0.08, 0.23]	0.115	4.187	0.000 ***	2-Choice RT	0.007 [−0.07, 0.09]	0.032	0.175	0.861
4-Choice RT	0.16 [0.09, 0.22]	0.119	4.514	0.000 ***	4-Choice RT	0.007 [−0.06, 0.08]	0.032	0.180	0.861
8-Choice RT	0.16 [0.08, 0.24]	0.136	4.091	0.000 ***	8-Choice RT	−0.01 [−0.09, 0.07]	0.035	−0.251	0.861
Visuo-Spatial Working Memory
Accuracy	−0.06 [−0.14, 0.02]	0.166	−1.530	0.126	Accuracy	−0.03 [−0.11, 0.05]	0.038	−0.704	0.657
Creative Writing
Create and Present	−0.23 [−0.30, −0.16]	0.150	−6.404	0.000 ***	Create and Present	−0.13 [−0.20, −0.05]	0.034	−3.321	0.003 **

Table 3. $R^2$ with the associated 95% CI for the significant models grouped by genotype, phenotype, and portion of phenotypic variance explained by the dyslexia phenotype that is due to dyslexia polygenic score.

	$R^2$ genotype	$R^2$ phenotype	Percentage of phenotypic variance due to genes
IQ subtests
Information	0.008 [0.00, 0.02]	0.038 [0.02, 0.06]	21.1%
Arithmetic	0.029 [0.01, 0.05]	0.046 [0.02, 0.07]	63%
Vocabulary	0.008 [0.00, 0.02]	0.031 [0.01, 0.05]	25.8%
Spatial	0.009 [0.00, 0.03]	0.030 [0.01, 0.05]	30%
Object Assembly	0.001 [0.00, 0.01]	0.007 [0.00, 0.02]	14.3%
Digit Symbol	0.017 [0.01, 0.03]	0.016 [0.00, 0.03]	100%
Digits Forward	0.01 [0.01, 0.02]	0.014 [0.01, 0.03]	71.4%
Working memory
Digits Backward	0.007 [0.00, 0.02]	0.005 [0.00, 0.02]	100%
Letter-Number Sequencing	0.018 [0.01, 0.03]	0.009 [0.00, 0.02]	100%
Elementary Cognitive Tasks
Inspection Time	0.000 [0.00, 0.01]	0.027 [0.01, 0.05]	0%
2-CRT	0.000 [0.00, 0.00]	0.015 [0.01, 0.03]	0%
4-CRT	0.000 [0.00, 0.00]	0.018 [0.01, 0.04]	0%
8-CRT	0.000 [0.00, 0.01]	0.017 [0.00, 0.04]	0%
Visuo-Spatial Working Memory
Accuracy	0.001 [0.00, 0.01]	0.003 [0.00, 0.02]	33.3%
Creative Writing
Create and Present	0.012 [0.003, 0.033]	0.040 [0.021, 0.069]	30%

Note 1. Variables showing 100% mediation have higher PGS than phenotypic variance.

Data availability statement

The full GWAS summary statistics for the 23andMe discovery data set are available through 23andMe to qualified researchers under an agreement with 23andMe that protects the privacy of the 23andMe participants. Datasets will be made available at no cost for academic use. Please visit https://research.23andme.com/collaborate/#dataset-access/ for more information and to apply to access the data. Note that 23andMe participants provided informed consent and volunteered to participate in the research online, under a protocol approved by the external AAHRPP-accredited IRB, Ethical & Independent (E&I) Review Services. As of 2022, E&I Review Services is part of Salus IRB (https://www.versiticlinicaltrials.org/salusirb).