DNA methylation at birth and fine motor ability in childhood: an epigenome-wide association study with replication

Figures & data

Table 1. Descriptive statistics in two cohorts.

	GenR (N = 925)	INMA (N = 326)
Child characteristics
Sex, % girls	50.8	48.2
Gestational age in weeks, mean (SD)	40.2 (1.5)	39.8 (1.4)
Prematurity, %	2.38	2.45
Age at measure of FTT, years, mean (SD)	9.8 (0.3)	6.8 (0.4)
Handedness, laterality quotient, mean (SD)	0.7 (0.5)	0.8 (0.5)
Finger-tapping test (FTT), number of taps, mean (SD)
Left-hand FTT	38.2 (5.6)	56.6 (8.8)
Right-hand FTT	41.1 (6.6)	66.0 (8.1)
Bimanual FTT (alternating)	35.1 (11.9)	NA
Maternal characteristics
Age at intake/delivery, years, mean (SD)	32.1 (4.1)	31.7 (4.1)
Sustained smoking during pregnancy, %	11.2	12.6
Educational level, %
Lower (below university degree)	32.5	68.0
Higher (university degree and above)	67.5	32.0

Note. Prematurity is defined as neonates at less than 37 weeks gestation.

Figure 1. Manhattan plots (Fig.1a. Left-hand; Fig.1b. Right-hand). showing EWAS between cord blood DNA methylation and finger tapping test at 10 years (N = 925). The horizontal line indicates a FDR threshold of q < 0.05. Top CpG sites are highlighted in green.

Table 2. Top 10 CpGs derived from the EWAS of the association between neonatal blood DNAm and right and left hand finger tapping test at 10 years in GenR; sorted by ascending p-value (N = 925).

CpGs	Chr	Pos	Nearest gene	Effect	SE	p	FDR
Outcome: right-hand FTT
cg07783800	chr1	235803662	GNG4	0.17	0.03	5.11E–08	0.023
cg14660125	chr4	89378460	HERC5	0.14	0.03	6.95E–07	0.159
cg20790998	chr1	68290436	GNG12	−0.18	0.04	1.31E–06	0.171
cg09469355	chr1	2161886	SKI	0.16	0.03	1.61E–06	0.171
cg26657045	chr5	60132712	ELOVL7	0.17	0.04	2.20E–06	0.171
cg13964781	chr19	14552350	PKN1	0.14	0.03	2.29E–06	0.171
cg26095658	chr2	71017887	FIGLA	−0.13	0.03	2.65E–06	0.171
cg11849213	chr14	65210900	PLEKHG3	0.16	0.03	3.28E–06	0.171
cg04477675	chr6	33168449	SLC39A7;RXRB	−0.14	0.03	3.35E–06	0.171
cg23468128	chr2	61108270	REL	−0.15	0.03	4.35E–06	0.200
Outcome: left-hand FTT
cg05136476	chr3	53190709	PRKCD*	0.15	0.03	1.20E–07	0.026
cg07783800	chr1	235803662	GNG4	0.16	0.03	1.70E–07	0.026
cg07638797	chr21	38792116	DYRK1A	0.19	0.04	2.12E–07	0.026
cg16705073	chr16	70472678	ST3GAL2	0.17	0.03	2.29E–07	0.026
cg10194627	chr13	74568601	KLF12	0.21	0.04	7.25E–07	0.067
cg09004351	chr7	5515555	FBXL18	0.15	0.03	2.20E–06	0.168
cg02019988	chr3	50311211	SEMA3B	−0.13	0.03	9.38E–06	0.404
cg19321991	chr1	213124472	VASH2	−0.20	0.04	1.02E–05	0.404
cg02960777	chr7	77562848	PHTF2	−0.14	0.03	1.05E–05	0.404
cg19870626	chr1	175889703	RFWD2*	0.13	0.03	1.07E–05	0.404

Note. FTT: finger-tapping test; Chr: chromosome; Pos: position; Effect, standardized regression coefficients, SE, standardized error. The full model is adjusted for sex, gestational age, age at FTT assessment, handedness, maternal age in take/delivery, maternal smoking during pregnancy, batch effects, estimated cell-type proportions.*Annotation based on University of California Santa Cruz Known Gene fills in the nearest gene within 10 MB.

Figure 2. Regional Association Plot for the Top DNA Methylation (CpG) Site cg07783800.

Note. On the top graph, the x-axis depicts the position in base pair (bp) (hg19) for the region of GNG4. The y-axis indicates the strength of association from EWAS with FTT. Each circle represents a CpG site. Red dashed line within the graph indicates the genome-wide significance threshold. The regulatory information and correlation matrix of other CpG sites in the region with the top hit are shown below the x-axis. Color intensity marks the strength of the correlation and color indicates the direction of the correlation. The figure was made using the R package coMET.