Association between dietary patterns reflecting one-carbon metabolism nutrients intake before pregnancy and placental DNA methylation

Figures & data

Table 1. Characteristics of the three dietary patterns resulting from the reduced rank regression method, described in details in [11].

	Varied and balanced	Vegetarian tendency	Bread and starchy food
High intake of main food groups^a	Low-fat milk, meat, liver, fish, eggs and egg dishes, cereals, mixed vegetables, chicory, leeks and cabbage, and broccoli	Fruits, chicory, mixed vegetables, cereals, and bread	Bread, sandwiches and rice, pasta and other grains
Low intake of food groups^a	Snacks and confectionery and sugar-sweetened beverages	Meat and liver	Low-fat milk, fruits, fruit juices, and sugar-sweetened beverages
Explained variation in nutrients intake^b	35%	14.4%	8.3%
Association with OCMnutrients^c
Positivecoefficient	B vitamins, choline, and methionine	B6 and B9 vitamins and betaine	Betaine
Negative coefficient	Betaine	Vitamin B12, choline and methionine	Vitamins B2, B6, and B9

^aHigh and low intake of main food groups with factor loading ≥ 0.20.

^bExplained variation in the overall nutrient variables from the reduced-rank regression

^cAssociation of the nutrient variables with the three dietary patterns.

Figure 1. Flow-chart of population selection.

Table 2. Characteristics of women selected for analysis (N = 573).

Sociodemographic data	Missing data n (%)	Population^a
Study centre	0 (0)	-
Poitiers		251 (44)
Nancy		322 (56)
Maternal age (years)	0 (0)	29.2 ± 5
Maternal education level	3 (0.5)	-
Lower secondary school		151 (26.5)
Upper secondary school		100 (17.5)
Post-secondary		123 (21.6)
Tertiary		196 (34.4)
Pregnancy
Gestational age (weeks)	0 (0)	39.3 ± 1.5
Primiparous	1 (0.15)	258 (45)
Smoking during pregnancy	16 (2.8)	-
No		390 (70)
1–9 cigarettes/day		138 (24.8)
At least 10 cigarettes/day		29 (5.2)
Vitamin supplementation	3 (0.5)
No		339 (59.5)
Before pregnancy		53 (9.3)
During pregnancy		129 (22.6)
Before and during pregnancy		49 (8.6)
BMI at conception, kg/m^2	10 (1.7)	22.9 ± 4.2
Child sex	0 (0)	-
Boy		302 (52.7)
Girl		271 (47.3)

^aDescriptive data n (%) and mean ± SD. BMI, body mass index.

Table 3. Association between dietary patterns or vitamin supplementation and global DNA methylation in different adjusted models.

	Alu (16.2 ± 1.0) *				LINE-1 (26.1 ± 1.9) *
Exposure	β ^a (SE)	P-value	β ^b (SE)	P-value	β ^a (SE)	P-value	β ^b (SE)	P-value
Dietary patterns
Varied and balanced	-0.02 (0.03)	0.60	-0.02 (0.03)	0.52	-0.10 (0.07)	0.16	-0.07 (0.07)	0.31
Vegetarian tendency	0.02 (0.04)	0.69	0.03 (0.04)	0.50	-0.13 (0.08)	0.11	-0.10 (0.08)	0.18
Bread and starchy food	0.03 (0.04)	0.52	0.03 (0.04)	0.41	-0.06 (0.09)	0.52	-0.05 (0.09)	0.58
Vitamin supplementation
No supplementation	Reference		Reference		Reference		Reference
Before pregnancy only	-0.14 (0.14)	0.29	-0.14 (0.14)	0.29	0.10 (0.29)	0.74	0.06 (0.28)	0.82
During pregnancy only	0.15 (0.09)	0.11	0.16 (0.09)	0.08	0.18 (0.20)	0.37	0.23 (0.20)	0.24
Before and during pregnancy	0.40 (0.14)	0.005	0.37 (0.14)	0.009	-0.07 (0.30)	0.80	-0.10 (0.29)	0.74

Median percentage of the four CpG sites in Alu and long interspersed nucleotide elements [LINE-1] as proxies of overall methylation level

Data are regression coefficients for an increase in one score unit for each dietary pattern.

*mean percentage methylation level

^aAdjusted models for study centre, maternal age, child sex, smoking during pregnancy, gestational age, batch effect and vitamin supplementation (model for dietary pattern), and adjusted mutually for the three dietary patterns (model for vitamin supplementation).

^bAdditional adjustment for estimated cellular composition.

P < 0.05. SE: standard error

Figure 2. Manhattan plots of epigenome-wide association results for ‘varied and balanced pattern’ within the placenta.

The red dashed line represents Bonferroni correction significance threshold (p = 1.0 × 10^–7). The direction of the associations is reported with negative effects below zero and positive effects above zero. Model adjusted for study centre, maternal age, child sex, gestational age, smoking during pregnancy, batch effect, cellular composition and surrogate variable analysis variables.

Figure 3. Quantile-quantile plot for regression model between scores on the ‘varied and balanced diet’ in the year before pregnancy and placental DNA methylation.

Model adjusted for study center, maternal age, child sex, gestational age, smoking during pregnancy, batch effect, cellular composition, and SVA variables.

Table 4. Dietary patterns in the year before pregnancy and differentially methylated regions (DMRs)^a of placental DNA in the EDEN cohort.

Exposure	Number of CpG sites	Chr	Position	Gene(s)	CpG site	DMR direction of association and individual CpG site β-value^b	P-value^c
Varied and balanced	8	Chr 3	37034730-37034956	EPM2AIP1, MLH1	cg10769891 cg19132762 cg23658326 cg11600697 cg21490561 cg00893636 cg03192963 cg06791151	Positive 0.0002466 0.0000365 0.0001607 -0.0002116 -0.0001209 -0.0000941 0.0000985 -0.0000509	0.003 0.05 0.81 0.04 0.49 0.45 0.68 0.54 0.58
Vegetarian tendency	6	Chr 19	9785647-9785919	ZNF562	cg10755961 cg24874111 cg18587364 cg20631204 cg14073063 cg14308647	Positive 0.0005334 -0.0006368 -0.0003679 -0.0002906 0.0001544 0.0003846	4.6.10^−18 0.04 0.09 0.46 0.40 0.53 0.03
	5	Chr 11	13690122-13690194	FAR1	cg02831587 cg26240185 cg03326059 cg10572969 cg24412501	Negative 0.0003768 -0.0000984 -0.0000360 -0.0000200 0.0003739	9.5.10^−10 0.04 0.17 0.49 0.77 0.04
Bread and starchy food	5	Chr 10	104628959-104629151	AS3MT	cg16989281 cg00086670 cg25143771 cg08856941 cg24592962	Negative -0.0040595 0.0000005 -0.0008883 -0.0008247 -0.0011958	0.04 0.01 0.99 0.53 0.07 0.0004
	8	Chr8	144635309-144635547	GSDMD	cg22012530 cg01134012 cg18198896 cg14721632 cg23090207 cg12686110 cg15541193 cg09317036	Negative -0.0021065 0.0004952 -0.0004702 -0.0011329 -0.0002147 -0.0005133 -0.0004292 -0.0006335	0.002 0.03 0.44 0.04 0.27 0.64 0.06 0.23 0.003
	3	Chr 5	110075158-110075285	SLC25A46	cg13505794 cg13911629 cg27366305	Positive -0.0029363 -0.0000855 -0.0014410	0.0008 0.01 0.85 0.003

^aDMRs determined with the use of dmrff [26]. All models were adjusted for child sex, study centre, maternal age, gestational age, smoking during pregnancy, batch effect, cell-type distribution estimated and SVA variables.

^bCoefficient associated with DMR or direction of the association. β-value reported for individual CpG sites.

^cAdjusted p-value associated with DMR and no-adjusted p-value for CpG sites.

Table 5. Dietary patterns in the year before pregnancy and differentially methylated regions (DMRs)^a of placental DNA, after adjustment for vitamin supplementation.

Exposure	Number of CpG sites	Chr	Position	Gene	CpG site	DMR direction of association and individual CpG site β-value^b	P-value^c
Varied and balanced	3	Chr 9	139940640-139941067	NPDC1	cg22952834 cg12611723 cg17902858	Positive 0.0002152 0.0014960 0.0010973	0.02 0.031 0.0001 0.0004
Vegetarian tendency	4 3	Chr 6 Chr 6	170599869-170600060 170599826-170599840	DLL1 DLL1	cg08273501 cg12024311 cg27139933 cg00474209 cg03394401 cg14497851 cg03815571	Negative -0.0002168 -0.0000268 -0.0000134 0.0012425 Negative 0.0038978 -0.0000644 0.0005043	5.3.10^−7 0.31 0.79 0.97 0.004 7.0.10^−3 0.008 0.55 0.40
	2 3	Chr 11 Chr 11	13690122-13690157 13690160-13690194	FAR1 FAR1	cg02831587 g10572969 cg03326059 cg10572969 cg24412501	Negative 0.0003705 -0.0001112 Negative -0.0000295 -0.0000240 0.0003721	3.7.10^−9 0.04 0.12 7.8.10^−3 0.57 0.73 0.05
Bread and starchy food	5	Chr 10	104628959-104629151	AS3MT	cg16989281 cg0086670 cg25143771 cg08856941 cg24592962	Negative -0.0040765 0.0000536 -0.0007242 -0.0008231 -0.0012140	0.02 0.01 0.94 0.61 0.07 0.0003
	8	Chr8	144635309-144635547	GSDMD	cg22012530 cg01134012 cg18198896 cg14721632 cg23090207 cg12686110 cg15541193 cg09317036	Negative -0.0020483 0.0005035 -0.0004714 -0.0010857 -0.0002096 -0.0005028 -0.0004105 -0.0006211	0.004 0.03 0.43 0.04 0.29 0.65 0.06 0.25 0.003
	3	Chr 5	110075158-110075285	SLC25A46	cg13505794 cg13911629 cg27366305	Positive -0.0029720 -0.0001567 -0.0013743	0.01 0.01 0.74 0.006
	4	Chr 19	52074293-52074348	ZNF175	cg18379413 cg18708075 cg26605406 cg01382982	Positive 0.0127613 0.0129549 0.0095819 0.0075372	0.006 0.003 0.02 0.21 0.26

^aDMRs determined with the use of dmrff [26]. All models were adjusted for child sex, study centre, maternal age, gestational age, smoking during pregnancy, batch effect, cell-type distribution estimated, surrogate variable analysis variables and vitamin supplementation.

^bCoefficient associated with DMR or direction of the association. β-value reported for individual CpG sites.

^cAdjusted p-value associated with DMR and no-adjusted p-value for CpG sites.

Lecorguillé M, Lioret S, de Lauzon-Guillain B, de Gavelle E, Forhan A, Mariotti F, Charles M-A, Heude B. Association between Dietary Intake of One-Carbon Metabolism Nutrients in the Year before Pregnancy and Birth Anthropometry. Nutrients [Internet]. 2020 [cited 2020 Mar 31];12:838. Available from: https://www.mdpi.com/2072-6643/12/3/838

 Google Scholar

Suderman M, Staley JR, French R, et al. dmrff: identifying differentially methylated regions efficiently with power and control. bioRxiv. Internet] 2018 [cited 2020 May 15];508556. Available from. []:. https://www.biorxiv.org/content/10.1101/508556v1

 Google Scholar