A Multi-omics Approach to Investigate the Inflammatory Response to Life Course Socioeconomic Position

Figures & data

Table 1. Summary characteristics of the study population by life course socioeconomic position.

Characteristics	Father’s occupational position (N = 158)			Participant’s education (N = 172)			Household’s highest occupational position (N = 160)			Participants with complete data (N = 155)
	Nonmanual	Manual	p-value^†	High	Low	p-value^†	Nonmanual	Manual	p-value^†	N% or mean (SD)
N	54 (34.2)	104 (65.8)		77 (44.8)	95 (55.2)		102 (63.7)	58 (36.2)
Age, years, mean (SD)	51.9 (8.1)	53.7 (7.8)	2.04 × 10^-1	50.5 (7.3)	54.8 (7.8)	2.34 × 10^-4	52.2 (7.9)	54.9 (7.8)	3.93 × 10^-2	53.2 (7.9)
Gender   – Women   – Men	45 (83.3) 9 (16.7)	75 (72.1) 29 (27.9)	1.71 × 10^-1	59 (76.6) 18 (23.4)	75 (78.9) 20 (21.1)	8.57 × 10^-1	76 (74.5) 26 (25.5)	45 (22.4) 13 (22.4)	8.07 × 10^-1	118 (76.1) 37 (23.9)
Cancer case	26 (48.1)	39 (37.5)	2.63 × 10^-1	28 (36.4)	41 (43.2)	4.55 × 10^-1	48 (47.1)	17 (29.3)	4.24 × 10^-2	63 (40.6)
Center^‡   – South   – Central   – North	1 (1.9) 34 (63.0) 19 (35.2)	11 (10.6) 46 (44.2) 47 (45.2)	3.21 × 10^-2	12 (15.6) 43 (55.8) 22 (28.6)	9 (9.5) 40 (42.1) 46 (48.4)	2.73 × 10^-2	7 (6.9) 56 (54.9) 39 (38.2)	5 (8.6) 25 (43.1) 28 (48.3)	0.3571444	11 (7.1) 79 (51.0) 65 (41.9)
BMI   – Missing	25.3 (3.6) –	25.8 (3.5) 2	4.33 × 10^-1	25.1 (3.3) –	26.2 (3.6) 1	3.36 × 10^-2	25.4 (3.4) –	26.2 (3.7) 2	1.61 × 10^-1	25.7 (3.5)
Smoking status   – Never   – Former   – Current   – Missing	23 (42.6) 15 (27.8) 16 (29.6) 0	56 (53.8) 25 (24.0) 22 (21.2) 1 (1)	3.42 × 10^-1	28 (36.4) 26 (33.8) 23 (29.9) –	56 (58.9) 19 (20.0) 20 (21.1) –	1.20 × 10^-2	45 (44.1) 29 (28.4) 28 (27.5) –	34 (59.6) 12 (21.1) 11 (19.3) 1	1.70 × 10^-1	78 (50.3) 40 (25.8) 37 (23.9)
Grams alcohol/day   – Missing	13.7 (19.3) –	9.2 (14) 1	1.30 × 10^-1	12 (16.4) –	9 (15.1) –	2.20 × 10^-1	10.8 (15.3) –	11.5 (17.7) 1	8.12 × 10^-1	10.9 (16.2)

Counts and percentages are reported for categorial variable, and means and SDs for continuous variables.

† p-value for difference was calculated using the Chi-squared test for categorical variables and the student’s t-test for continuous variables.

‡ North: Turin & Varese; Central: Florence; South: Naples & Ragusa.

SD: Standard deviation.

Figure 1. Description of the inflammatory methylome.

Frequency of the 61 cis-eMS defining the inflammatory methylome by (A) inflammatory subpathway; (B) correlation between DNA methylation and gene expression; (C) physical distribution and (D) CpG island and neighborhood context.

eMS: Expression methylation site.

Table 2. Linear regression results for the inflammatory methylome and each of the three life course socioeconomic position factors in the European Prospective Investigation into Cancer and Nutrition-Italy participants from EnviroGenoMarkers (N = 155).

Inflammatory methylome scores	Father’s occupational position		Participant’s education		Highest household occupational position
	β (SE)	p-value	β (SE)	p-value	β (SE)	p-value
Inflammatory methylome score	-0.0023 (0.0028)	4.18 × 10^-1	-0.0075 (0.0028)	6.72 × 10^-3	-0.0076 (0.0028)	7.37 × 10^-3
Inflammatory methylome z-score	-2.325 (4.0788)	5.70 × 10^-1	-9.7219 (3.9778)	1.57 × 10^-2	-11.4191 (4.0258)	5.20 × 10^-3
Principal component 1	-0.713 (0.9193)	4.39 × 10^-1	-1.6264 (0.9055)	7.45 × 10^-2	-2.0508 (0.9172)	2.69 × 10^-2

Results are given for Model 1 controlling for age, gender, lymphoma and breast cancer case–control status, phase and center.

SE: Standard error.

Table 3. Life course multiple regression analyses and the inflammatory methylome. Results are presented for the inflammatory methlyome score (A), the inflammatory methylome z-score (B) and the first PC (C). Estimates are based on 155 participants with complete socioeconomic position, lifestyle information and DNA methylation data.

Inflammatory methylome scores			Model A		Model B-1		Model B-2		Model C		Model D		Fully adjusted model^†
(A) Inflammatory methylome score
Variables	Levels	β (SE)	p-value	β (SE)	p-value	β (SE)	p-value	β (SE)	p-value	β (SE)	p-value	β (SE)	p-value
Father’s occupational position	Manual	-0.002 (0.003)	4.18 × 10^-1	0.002 (0.003)	6.22 × 10^-1	0 (0.003)	9.96 × 10^-1	0.002 (0.003)	5.07 × 10^-1	0.002 (0.003)	5.12 × 10^-1	0.002 (0.002)	3.87 × 10^-1
Participant’s education	Low			-0.008 (0.003)	8.67 × 10^-3			-0.006 (0.003)	8.05 × 10^-2	-0.005 (0.003)	1.39 × 10^-1	-0.006 (0.003)	2.98 × 10^-2
Highest household occupational position	Manual					-0.008 (0.003)	1.09 × 10^-2	-0.005 (0.003)	1.03 × 10^-1	-0.005 (0.003)	1.07 × 10^-1	-0.003 (0.002)	1.76 × 10^-1
BMI										0 (0)	3.02 × 10^-1	0 (0)	8.94 × 10^-1
Smoking status	Former									0.002 (0.004)	5.14 × 10^-1	0.001 (0.003)	8.04 × 10^-1
	Current									-0.001 (0.004)	7.13 × 10^-1	0.001 (0.003)	6.58 × 10^-1
Alcohol										0 (0)	7.18 × 10^-1	0 (0)	7.91 × 10^-1
(B) Inflammatory methylome z-score
Variables	Levels	β (SE)	p-value	β (SE)	p-value	β (SE)	p-value	β (SE)	p-value	β (SE)	p-value	β (SE)	p-value
Father’s occupational position	Manual	-2.325 (4.079)	5.70 × 10^-1	2.791 (4.523)	5.38 × 10^-1	1.259 (4.192)	7.64 × 10^-1	3.706 (4.506)	4.12 × 10^-1	3.969 (4.613)	3.91 × 10^-1	3.864 (3.222)	2.32 × 10^-1
Participant’s education	Low			-11.003 (4.494)	1.55 × 10^-2			-7.073 (4.889)	1.50 × 10^-1	-5.481 (4.971)	2.72 × 10^-1	-6.129 (3.474)	7.99 × 10^-2
Highest household occupational position	Manual					-11.811 (4.243)	6.09 × 10^-3	-9.038 (4.642)	5.35 × 10^-2	-9.186 (4.706)	5.29 × 10^-2	-6.105 (3.311)	6.73 × 10^-2
BMI										-0.783 (0.568)	1.70 × 10^-1	-0.224 (0.399)	5.75 × 10^-1
Smoking status	Former									5.024 (5.357)	3.50 × 10^-1	2.356 (3.752)	5.31 × 10^-1
	Current									-0.946 (5.101)	8.53 × 10^-1	2.772 (3.585)	4.41 × 10^-1
Alcohol										0.086 (0.136)	5.30 × 10^-1	0.006 (0.096)	9.54 × 10^-1
(C) Principal component 1
Variables	Levels	β (SE)	p-value	β (SE)	p-value	β (SE)	p-value	β (SE)	p-value	β (SE)	p-value	β (SE)	p-value
Father’s occupational position	Manual	-0.713 (0.919)	4.39 × 10^-1	0.055 (1.031)	9.58 × 10^-1	-0.1 (0.955)	9.17 × 10^-1	0.222 (1.032)	8.30 × 10^-1	0.251 (1.06)	8.14 × 10^-1	0.207 (0.542)	7.03 × 10^-1
Participant’s education	Low			-1.652 (1.024)	1.09 × 10^-1			-0.932 (1.119)	4.06 × 10^-1	-0.625 (1.143)	5.85 × 10^-1	-0.781 (0.584)	1.84 × 10^-1
Highest household occupational position	Manual					-2.02 (0.967)	3.85 × 10^-2	-1.654 (1.063)	1.22 × 10^-1	-1.663 (1.081)	1.26 × 10^-1	-0.76 (0.557)	1.74 × 10^-1
BMI										-0.155 (0.13)	2.37 × 10^-1	-0.004 (0.067)	9.55 × 10^-1
Smoking status	Former									1.027 (1.231)	4.06 × 10^-1	0.26 (0.631)	6.81 × 10^-1
	Current									-0.101 (1.172)	9.31 × 10^-1	0.871 (0.603)	1.51 × 10^-1
Alcohol										0.013 (0.031)	6.81 × 10^-1	-0.01 (0.016)	5.44 × 10^-1

† Model adjusted for cell blood composition (see Methods section).

SE: Standard error.

Figure 2. Boxplot summarizing the distribution of the inflammatory methylome (on the left) and corresponding inflammatory transcriptome (on the right) score by life course socioeconomic position.

(A) Father’s occupational position; (B) participant’s education and (C) the highest household occupational position from 155 EPIC-Italy participants. t-test mean comparison p-values are reported for each score by SEP.

EPIC-Italy: European Prospective Investigation into Cancer and Nutrition-Italy; SEP: Socioeconomic position.