Introduction
Methods
The CoLaus|PsyCoLaus cohort
The Diagnostic Interview for Genetic Studies
-
Did your parents fight with each other frequently? (interparental violence)
-
Did your parents ever do anything that frightened you (like lock you in a closet)? (fear of maltreatment)
Inflammatory markers and WBC counts
Statistical analysis
-
Adjustment for multiple testing is appropriate under specific conditions including homogeneous items (as well as large Ns, precise measurements, homogeneous conditions, etc.); in contrast, the diseases/disorders we are investigating subsume heterogeneous conditions and comprise different subtypes; this applies not only to grouped disorders but similarly also to most of the specific disorders or diseases comprised in this study; one part of the analysis strategy is to prioritize the β-error over the α-error, that is, to increase the probability to account for or to detect minor subtypes
-
Another part of the analysis strategy is to focus on pattern recognition, explicitly through the LCA in this study, but also implicitly in analyses of groups of markers and disorders; pattern recognition is prioritized over analysis of single conditions; adjustment for multiple testing is uncommon in any pattern recognition analysis such as involving LCA, factor analysis, and correspondence analysis (see also [45])
Results
All | Men | Women | |
---|---|---|---|
Infections | |||
Chickenpox | 3733 (83.3%) | 1657 (80.8%) | 2076 (85.5%) |
Measles | 3323 (75.7%) | 1442 (72.0%) | 1881 (78.8%) |
Mumps | 2720 (60.8%) | 1291 (62.9%) | 1429 (59.1%) |
Rubella | 283 (5.3%) | 62 (2.7%) | 221 (8.5%) |
Scarlet fever | 216 (4.4%) | 80 (3.5%) | 136 (5.2%) |
Pertussis | 377 (7.7%) | 113 (5.0%) | 264 (10.1%) |
Herpes labialis | 767 (15.7%) | 260 (11.5%) | 507 (19.4%) |
Atopies | |||
Atopic asthma | 291 (6.0%) | 107 (4.7%) | 184 (7.0%) |
Other asthma | 373 (7.7%) | 141 (6.2%) | 232 (8.9%) |
Atopic eczema | 230 (4.7%) | 72 (3.2%) | 158 (6.1%) |
Other eczema | 314 (6.4%) | 125 (5.5%) | 189 (7.2%) |
Hay fever | 890 (18.3%) | 420 (18.6%) | 470 (18.0%) |
Urticaria | 179 (3.7%) | 59 (2.6%) | 120 (4.6%) |
Drug allergy | 493 (10.1%) | 164 (7.2%) | 329 (12.6) |
Adverse childhood experiences | |||
Fights among parents | 609 (12.6%) | 264 (11.8%) | 345 (13.4%) |
Fear of parental maltreatment | 464 (9.6%) | 191 (8.5%) | 273 (10.5%) |
Trauma below age of 10 | 189 (3.9%) | 56 (2.5%) | 133 (5.1%) |
All | Men | Women | |
---|---|---|---|
Chronic inflammatory diseases | |||
Ulcer | 265 (5.4%) | 136 (6.0%) | 129 (4.9%) |
Irritable bowel syndrome | 188 (3.9%) | 52 (2.3%) | 136 (5.2%) |
Cystitis | 1069 (21.9%) | 116 (5.1%) | 953 (36.5%) |
Acne | 475 (9.7%) | 191 (8.4%) | 284 (10.9%) |
Psoriasis | 220 (4.5%) | 108 (4.8%) | 112 (4.3%) |
Migraine | 664 (13.6%) | 196 (8.7%) | 468 (17.9%) |
Neurodevelopmental/mental disorders1 | |||
Neurodevelopmental disorders | 353 (7.2%) | 214 (9.5%) | 139 (5.3%) |
Early anxiety disorders | 1104 (22.7%) | 377 (16.7%) | 727 (27.9%) |
Late anxiety disorders | 655 (16.2%) | 233 (10.3%) | 422 (16.2%) |
Mood disorders | 2161 (44.3%) | 770 (34.0%) | 1391 (53.3%) |
Substance disorders | 645 (13.2%) | 488 (21.6%) | 157 (6.0%) |
All | Men | Women | |
---|---|---|---|
White blood cell counts1 | |||
Total leukocytes (in 1000/mm3) | 6.25 (6.19–6.32) | 6.40 (6.30–6.49) | 6.13 (6.05–6.21) |
Neutrophils % | 0.548 (0.545–0.551) | 0.545 (0.540–0.550) | 0.550 (0.546–0.555) |
Basophils % | 0.0058 (0.0057–0.0059) | 0.0056 (0.0054–0.0057) | 0.0060 (0.0059–0.0062) |
Eosinophils % | 0.0294 (0.0288–0.0301) | 0.0316 (0.0307–0.0326) | 0.0276 (0.0268–0.0284) |
Lymphocytes % | 0.326 (0.323–0.329) | 0.321 (0.317–0.326) | 0.330 (0.326–0.334) |
Monocytes % | 0.0868 (0.0860–0.0876) | 0.0924 (0.0912–0.0936) | 0.0821 (0.0812–0.0831) |
Inflammatory markers at baseline | |||
IL-6 (pg/ml) | 8.15 (6.46–9.84) | 8.11 (5.55–10.67) | 8.19 (5.93–10.44) |
IL-1β (pg/ml) | 4.25 (3.49–5.02) | 4.31 (3.38–5.24) | 4.20 (3.03–5.38) |
TNF-α (pg/ml) | 6.62 (4.95–8.29) | 5.52 (4.37–6.66) | 7.57 (4.62–10.53) |
hsCRP (mg/l) | 1.81 (1.76–1.87) | 1.73 (1.65–1.80) | 1.89 (1.81–1.97) |
Inflammatory markers at follow-up 1 | |||
IL-6 (pg/ml) | 17.54 (15.39–19.69) | 17.53 (14.45–20.60) | 17.56 (14.56–20.55) |
IL-1β (pg/ml) | 4.45 (3.84–5.06) | 4.53 (3.81–5.24) | 4.39 (3.45–5.34) |
TNF-α (pg/ml) | 10.46 (8.44–12.47) | 10.08 (8.57–11.59) | 10.78 (7.27–14.29) |
hsCRP (mg/l) | 1.89 (1.83–1.95) | 1.77 (1.69–1.85) | 1.98 (1.90–2.06) |
Immune-mediated classes derived from LCA
Fit statistics | 1-class model | 2-class model | 3-class model | 4-class model | 5-class model | 6-class model |
---|---|---|---|---|---|---|
Men | ||||||
AIC | 21,775.3 | 21,055.2 | 20,801.7 | 20,639.2 | 20,604.3 | 20,599.4 |
BIC | 21,872.7 | 21,255.5 | 21,105.1 | 21,045.7 | 21,113.8 | 21,211.9 |
ABIC | 21,818.6 | 21,144.3 | 20,936.7 | 20,820.1 | 20,831.1 | 20,872.0 |
LMR-LRT. adj. | 750.8 | 287.4 | 197.0 | 70.4 | 40.6 | |
p-value | < 0.001 | < 0.001 | 0.052 | 0.648 | 0.016 | |
Women | ||||||
AIC | 30,328.7 | 29,729.7 | 29,466.4 | 29,262.3 | 29,186.2 | 29,148.4 |
BIC | 30,428.4 | 29,935.1 | 29,777.4 | 29,678.9 | 29,708.3 | 29,776.2 |
ABIC | 30,374.4 | 29,823.8 | 29,609.0 | 29,453.3 | 29,425.6 | 29,436.2 |
LMR-LRT. adj. | 630.5 | 297.2 | 238.4 | 111.4 | 73.2 | |
p-value | < 0.001 | < 0.001 | 0.003 | 0.002 | 0.106 |
Immune-mediated classes differ regarding socioeconomic and sociodemographic features
Neutral class | Resilient class | Atopic class | Mixed class | ACE class | Overall | |
---|---|---|---|---|---|---|
Men | ||||||
N | 1337 | 523 | 131 | 177 | 96 | 2264 |
SES score | 3.56 (3.50–3.63) | 3.33 (3.23–3.44) | 3.93 (3.73–4.13) | 3.77 (3.60–3.94) | 3.27 (3.00–3.54) | 3.53 (3.48–3.59) |
Mean age | 53.6 (53.0–54.2) | 54.4 (53.4–55.4) | 50.1 (48.2–51.9) | 53.3 (51.6–55.0) | 51.5 (49.3–53.6) | 53.5 (53.0–53.9) |
Women | ||||||
N | 1512 | 509 | 186 | 255 | 148 | 2610 |
SES score | 3.19 (3.12–3.25) | 3.20 (3.09–3.31) | 3.39 (3.21–3.57) | 3.44 (3.29–3.59) | 2.95 (2.73–3.16) | 3.21 (3.17–3.26) |
Mean age | 54.7 (54.2–55.3) | 56.4 (55.4–57.5) | 51.9 (50.2–53.5) | 55.2 (54.0–56.5) | 51.1 (49.7–52.6) | 54.7 (54.3–55.1) |
Immune-mediated classes differ regarding WBC counts and inflammatory markers
Immune-mediated classes’ associations with chronic inflammatory diseases and neurodevelopmental/mental disorders
Neutral class | Resilient class | Atopic class | Mixed class | ACE class | |
---|---|---|---|---|---|
Men | |||||
Ulcer | 1 (ref.) | 1.6 (1.1–2.3) | 1.0 (0.4–2.1) | 0.7 (0.3–1.6) | 0.7 (0.3–2.1) |
Irritable bowel syndrome | 1 (ref.) | 1.0 (0.5–2.1) | 3.0 (1.3–7.0) | 2.5 (1.1–5.6) | 1.1 (0.3–4.8) |
Cystitis | 1 (ref.) | 0.7 (0.4–1.3) | 3.2 (1.8–5.7) | 3.3 (1.9–5.5) | 1.5 (0.6–3.6) |
Acne | 1 (ref.) | 0.7 (0.5–1.1) | 1.4 (0.8–2.5) | 1.8 (1.1–2.8) | 0.7 (0.3–1.7) |
Psoriasis | 1 (ref.) | 0.7 (0.4–1.1) | 0.3 (0.1–1.2) | 1.3 (0.7–2.5) | 1.2 (0.5–2.9) |
Migraine | 1 (ref.) | 1.1 (0.7–1.6) | 1.8 (1.1–3.2) | 2.3 (1.5–3.6) | 1.3 (0.6–2.6) |
Women | |||||
Ulcer | 1 (ref.) | 1.3 (0.8–2.1) | 1.5 (0.8–2.9) | 1.4 (0.8–2.5) | 3.1 (1.8–5.4) |
Irritable bowel syndrome | 1 (ref.) | 1.5 (0.9–2.4) | 2.0 (1.1–3.8) | 2.9 (1.8–4.8) | 3.7 (2.1–6.6) |
Cystitis | 1 (ref.) | 1.0 (0.8–1.2) | 2.1 (1.5–2.8) | 1.9 (1.5–2.5) | 2.2 (1.5–3.0) |
Acne | 1 (ref.) | 0.9 (0.6–1.3) | 1.1 (0.6–1.7) | 1.5 (1.0–2.2) | 1.8 (1.1–2.8) |
Psoriasis | 1 (ref.) | 0.9 (0.5–1.5) | 1.0 (0.5–2.1) | 0.9 (0.5–1.8) | 1.6 (0.8–3.2) |
Migraine | 1 (ref.) | 0.9 (0.7–1.2) | 1.7 (1.2–2.4) | 1.2 (0.9–1.7) | 1.2 (0.8–1.8) |
Neutral class | Resilient class | Atopic class | Mixed class | ACE class | |
---|---|---|---|---|---|
Men | |||||
Neurodevelopmental disorders | 1 (ref.) | 0.8 (0.5–1.2) | 1.7 (1.0–3.0) | 2.0 (1.3–3.2) | 4.0 (2.4–6.5) |
Early anxiety disorders | 1 (ref.) | 0.8 (0.6–1.1) | 1.1 (0.7–1.8) | 2.0 (1.4–2.8) | 2.7 (1.7–4.3) |
Late anxiety disorders | 1 (ref.) | 0.7 (0.5–1.0) | 1.2 (0.7–2.1) | 1.5 (1.0–2.4) | 1.6 (0.9–2.9) |
Mood disorders | 1 (ref.) | 0.8 (0.7–1.0) | 1.5 (1.0–2.2) | 1.8 (1.3–2.5) | 2.3 (1.5–3.4) |
Substance disorders | 1 (ref.) | 0.9 (0.7–1.2) | 1.1 (0.7–1.6) | 1.1 (0.8–1.6) | 1.8 (1.1–2.8) |
Women | |||||
Neurodevelopmental disorders | 1 (ref.) | 0.6 (0.3–1.0) | 0.9 (0.4–1.8) | 1.6 (0.9–2.6) | 3.8 (2.3–6.2) |
Early anxiety disorders | 1 (ref.) | 0.7 (0.5–0.9) | 1.6 (1.2–2.2) | 1.4 (1.1–1.9) | 3.0 (2.1–4.2) |
Late anxiety disorders | 1 (ref.) | 0.8 (0.6–1.1) | 1.2 (0.8–1.8) | 1.6 (1.1–2.2) | 2.7 (1.9–4.0) |
Mood disorders | 1 (ref.) | 0.9 (0.7–1.0) | 1.1 (0.8–1.5) | 1.4 (1.1–1.9) | 2.2 (1.5–3.2) |
Substance disorders | 1 (ref.) | 0.6 (0.4–1.0) | 1.8 (1.0–3.0) | 1.6 (1.0–2.6) | 2.7 (1.6–4.6) |