Prenatal Socioeconomic Disadvantage and Epigenetic Alterations at Birth Among Children Born to White British and Pakistani Mothers in the Born in Bradford Study

Figures & data

Table 1. Parent and Child Sociodemographic and Clinical Characteristics.

	Total Sample (N = 948)	Children Born to White British Mothers (N = 455)	Children Born to Pakistani Mothers (N = 493)	P-value
Child characteristics
Sex, N (%)				0.7808
Male	492 (51.9)	234 (51.4)	258 (52.3)
Female	456 (48.1)	221 (48.6)	235 (47.7)
Gestational age (weeks), mean (± SE)	39.6 (± 0.1)	39.7 (± 0.1)	39.6 (± 0.1)	0.1137
Birthweight (grams), mean (± SE)	3279.6 (± 16.5)	3378.5 (± 25.1)	3188.2 (± 20.9)	<0.0001*
Parental characteristics
Mother’s age at time of child’s birth (years), mean (± SE)	27.4 (± 0.2)	26.8 (± 0.3)	28.0 (± 0.3)	0.0026*
Mother’s smoking status during pregnancy, N (%)^a				<0.0001*
No	778 (82.2)	301 (66.2)	477 (97.0)
Yes	169 (17.8)	154 (33.8)	15 (3.0)
Mother’s alcohol use during pregnancy, N (%)^a				<0.0001*
No	752 (79.4)	262 (57.6)	490 (99.6)
Yes	195 (20.6)	193 (42.4)	2 (0.4)
Mother’s body mass index at booking^b(kg/m^2), mean (± SE)	26.4 (± 0.2)	27.0 (± 0.3)	25.8 (± 0.2)	0.0014*
Mother’s marital status, N (%)^c				<0.0001*
Married and living with partner	619 (65.4)	163 (35.9)	456 (92.7)
Not married and living with partner	174 (18.4)	173 (38.1)	1 (0.2)
Not living with partner	153 (16.2)	118 (26.0)	35 (7.1)
Mother’s education level, N (%)^d				<0.0001*
< 5 GCSE equivalent	224 (23.8)	88 (19.5)	136 (27.8)
5 GCSE equivalent	314 (33.3)	163 (36.1)	151 (30.8)
A-level equivalent	149 (15.8)	86 (19.0)	63 (12.9)
> A-level equivalent	213 (22.6)	84 (18.6)	129 (26.3)
Other	42 (4.5)	31 (6.9)	11 (2.2)
Mother’s employment status, N (%)^a				<0.0001*
Employed	400 (42.2)	285 (62.6)	115 (23.4)
Unemployed	254 (26.8)	127 (27.9)	127 (25.8)
Never employed	293 (30.9)	43 (9.5)	250 (50.8)
Mother’s housing tenure^e				<0.0001*
Own	122 (13.0)	14 (3.1)	108 (22.3)
Mortgage	457 (48.7)	239 (52.8)	218 (44.9)
Rent	359 (38.3)	200 (44.2)	159 (32.8)
Mother’s receipt of means-tested benefits				0.0002*
No	543 (57.3)	289 (63.5)	254 (51.5)
Yes	405 (42.7)	166 (34.5)	239 (48.5)
Mother’s subjective financial security^a
Living comfortably or doing alright	647 (68.3)	321 (70.6)	326 (66.1)	0.2307
Just about getting by, quite difficult or very difficult	300 (31.7)	134 (29.4)	166 (33.7)
Mother’s index of multiple deprivation quintile, N (%)				<0.0001*
1 (most deprived)	611 (64.5)	210 (46.2)	401 (81.3)
2	173 (18.3)	111 (24.4)	62 (12.6)
3	105 (11.1)	81 (17.8)	24 (4.9)
4	41 (4.3)	37 (8.1)	4 (0.8)
5 (least deprived)	18 (1.9)	16 (3.5)	2 (0.4)
Father’s education level, N (%)^f				0.0031*
< 5 GCSE equivalent	159 (21.2)	79 (21.8)	80 (20.7)
5 GCSE equivalent	239 (31.9)	125 (34.4)	114 (29.5)
A-level equivalent	101 (13.5)	53 (14.6)	48 (12.4)
> A-level equivalent	211 (28.2)	76 (20.9)	135 (34.9)
Other	39 (5.2)	29 (8.0)	10 (2.6)
Father’s employment status, N (%)^g				<0.0001*
Employed – non-manual occupation	366 (40.5)	220 (51.9)	146 (30.5)
Employed – manual occupation	304 (33.7)	115 (27.1)	189 (39.5)
Self-employed	147 (16.3)	46 (10.8)	101 (21.1)
Unemployed or student	86 (9.5)	43 (10.1)	43 (9.0)

*p-value < 0.05. ^aN = 947, ^bN = 913, ^cN = 946, ^dN = 942, ^eN = 938, ^fN = 749, ^gN = 903. SE; standard error.

Table 2. Association Between Prenatal Socioeconomic Disadvantage and Cord Blood DNAm Among Children in the Born in Bradford Study.

					Model 1				Model 2				Model 3
	Probe	Closest gene	Genomic location	Relation to CpG island	β	SE	P-value	Δ % DNAm	β	SE	P-value	Δ % DNAm	β	SE	P-value	Δ % DNAm
Housing tenure
Own vs. rent^a
	Cg07094228	–	–	–	0.260	0.045	1.23E-08	3.56%	0.252	0.046	7.54E-08	3.46%	0.253	0.046	7.03E-08	3.47%
Father’s occupation
Manual vs. non-manual^a
	Cg22930484	–	–	–	0.188	0.031	3.20E-09	3.20%	0.196	0.033	2.69E-09	3.33%	0.198	0.033	1.8E-09	3.36%
IMD quintile
2 vs. 1^a
	Cg01181499	–	–	N Shore	0.206	0.039	1.61E-07	1.82%	0.204	0.039	2.41E-07	1.81%	0.206	0.039	1.91E-07	1.82%
4 vs. 1^a
	Cg09777657	RAI1	5ʹUTR	–	−0.451	0.075	2.23E-09	−4.72%	−0.434	0.078	6.71E-08	−4.56%	−0.431	0.077	2.53E-08	−4.53%
	Cg16785213	GABARAPL2	TSS1500	N Shore	−0.337	0.067	4.47E-07	−2.40%	−0.335	0.067	8.08E-07	−2.39%	−0.331	0.067	1.02E-06	−2.36%
	Cg15736726	IQCJ	TSS1500	–	−0.413	0.076	7.26E-07	−3.30%	−0.451	0.084	1.21E-07	−3.64%	−0.451	0.084	1.20E-07	−3.64%
5 vs. 1^b
	Cg01544807	POLB	TSS1500	N Shore	−0.254	0.045	2.71E-06	−0.31%	−0.263	0.046	2.09E-08	−0.32%	−0.26	0.046	2.84E-08	−0.31%
	Cg06703304	DUS2L;DDX28	TSS200;1stExon;5ʹUTR	Island	−0.353	0.047	1.13E-13	−0.37%	−0.380	0.049	1.45E-14	−0.40%	−0.380	0.049	1.80E-04	−0.40%
	Cg10666628	HNRNPH1	1stExon;5ʹUTR	Island	−0.396	0.058	2.31E-12	−0.49%	−0.415	0.058	1.42E-12	−0.51%	−0.415	0.058	1.53E-12	−0.51%
	Cg12491688	CASC4	TSS1500	N Shore	−0.351	0.07	6.00E-07	−0.79%	−0.374	0.072	2.96E-07	−0.84%	−0.373	0.072	3.11E-07	−0.83%
	Cg16414852	SULT1B1	5ʹUTR	–	0.513	0.102	6.80E-07	8.86%	0.472	0.106	9.67E-06	8.15%	0.464	0.106	1.33E-05	8.01%
	Cg24214261	LIMCH1	5ʹUTR;Body	–	0.606	0.116	1.94E-07	10.42%	0.475	0.118	6.08E-05	8.15%	0.466	0.118	8.10E-05	7.99%
	Cg27638126	MEOX2	Body	–	−0.723	0.141	3.48E-07	−1.99%	−0.684	0.146	3.24E-06	−1.90%	−0.677	0.146	4.10E-06	−1.89%

Model 1 adjusted for mother’s age, race/ethnicity, and education level as well as cell-type fraction (N = 932 for model with housing tenure, N = 897 for model with father’s occupation and N = 942 for model with IMD quintile). Model 2 additionally adjusted for mother’s smoking status, alcohol use, and booking BMI (N = 898 for model with housing tenure, N = 863 for model with father’s occupation, N = 907 for model with IMD quintile). Model 3 additionally adjusted for child’s gestational age and birthweight (N = 898 for model with housing tenure, N = 863 for model with father’s occupation, N = 907 for model with IMD quintile). ^aAssociation for which the false discovery rate (FDR) threshold of p < 0.05 was met. ^bAssociation for which both the FDR threshold of p < 0.05 as well as a permutation-based threshold of p ≤ 8.00e-06 were met. β; beta coefficient from model with m-values, Δ % DNAm; difference in percentage of methylation, SE; standard error, TSS; transcription start site, UTR; untranslated region, closest gene; UCSC annotated gene, genomic location; UCSC gene region feature category, relation to CpG island; UCSC relation to CPG islands.

Table 3. Association Between Prenatal Socioeconomic Disadvantage and Cord Blood DNAm Among Children in the Born in Bradford Study, Stratified by Maternal Ethnicity.

					Model 1				Model 2				Model 3
	Probe	Closest gene	Genomic location	Relation to CpG island	β	SE	P-value	Δ% DNAm	β	SE	P-value	Δ% DNAm	β	SE	P-value	Δ% DNAm
Children Born to White British Mothers
Father’s occupation
Student or unemployed vs. non-manual^a
Cg05709124		C2orf82	3ʹUTR	Island	−0.278	0.048	1.5E-08	−0.21%	−0.274	0.051	1.5E-07	−0.21%	−0.278	0.052	1.2E-07	−0.21%
IMD quintile
4 vs. 1^a
	Cg25379161	C5orf41	TSS1500	N Shore	−0.662	0.125	2.0E-07	−5.97%	−0.680	0.129	2.2E-07	−6.10%	−0.653	0.129	5.8E-07	−5.89%
5 vs. 1^b
	Cg08940732	–	–	–	−0.443	0.072	1.5E-09	−4.26%	−0.460	0.073	5.9E-10	−4.42%	−0.452	0.072	1.1E-09	−4.35%
	Cg19350003	–	–	–	−0.859	0.147	1.1E-08	−4.78%	−0.902	0.153	7.6E-09	−4.96%	−0.886	0.153	1.3E-08	−4.89%
Children Born to Pakistani Mothers
IMD quintile
2–5 vs. 1^a
Cg19219463		SLC6A17	–	Body	−0.283	0.048	4.9E-09	−2.68%	−0.276	0.049	2.7E-08	−2.63%	−0.276	0.490	2.6E-08	−2.62%

Model 1 adjusted for mother’s age and education level as well as cell-type fraction (N=452 among children born to White British mothers and N=490 among children born to Pakistani mothers). Model 2 additionally adjusted for mother’s smoking status, alcohol use (White British mothers only), and body mass index (kg/m2) (N=437 among children born to White British mothers and N=470 among children born to Pakistani mothers). Model 3 additionally adjusted for child’s gestational age and birthweight (N=437 among children born to White British mothers and N=470 among children born to Pakistani mothers). ^aAssociation for which the false discovery rate (FDR) threshold of p <0.05 was met. ^bAssociation for which both the FDR threshold of p <0.05 and permutation-based threshold of p ≤ 8.00e–06 was met. β; beta coefficient from model with m-values, Δ % DNAm; difference in percentage of methylation, SE; standard error, TSS; transcription start site, UTR; untranslated region, closest gene; UCSC annotated gene, genomic location; UCSC gene region feature category, relation to CpG island; UCSC relation to CpG islands.

Data availability Statement

The data that support the findings of this study are available upon request from the Born In Bradford Study team. https://borninbradford.nhs.uk/