3 Methylation

Author: Lucas Toshio Ito
lucas.toshio.ito@gmail.com
Universidade Federal de São Paulo (UNIFESP)

Last updated: March 16, 2026

Counts represent raw availability before modality-specific quality control. Cumulative cases are participants who met the phenotype definition at any observed timepoint; missing assessments are skipped.

Psychiatric Disorders (DAWBA):

Attention-Deficit/Hyperactivity Disorder (ADHD): dcanyhk
Anxiety Disorder: dcpanic; dcagor; dcgena; dcsoph; dcspph
Bipolar Disorder / Mania: dcmania
Eating Disorder: dceat
Major Depressive Disorder (MDD): dcmadep
Obsessive–Compulsive Disorder (OCD): dcocd
Psychosis: dcpsych
Post-Traumatic Stress Disorder (PTSD): dcptsd
Any Psychiatric Disorder: dcany

Suicidality variables (C-SSRS):

Suicidal Ideation (SI): p_colbi1_lt, p_colbi2_lt
Suicide Attempt (SA): p_colbsb1a_lt, p_colbsb2a_lt, p_colbsb3a_lt

3.1 Demographic Characteristics

Demographic Characteristics of the Study Sample
Variable	Wave0 N = 369¹	Wave1 N = 371¹	Wave2 N = 326¹	Overall N = 457²
Sex at birth
Male	218 (59.1%)	216 (58.2%)	188 (57.7%)	264 (57.8%)
Female	151 (40.9%)	155 (41.8%)	138 (42.3%)	193 (42.2%)
Age
Mean (SD)	10.6 (1.8)	14.3 (1.9)	17.8 (1.9)	23.0 (2.4)
Median (Q1-Q3)	10.4 (9.1-11.8)	14.2 (12.9-15.6)	17.7 (16.4-19.3)	23.1 (21.5-24.6)
State
RS	144 (39.0%)	159 (42.9%)	141 (43.3%)	199 (43.5%)
SP	225 (61.0%)	212 (57.1%)	185 (56.7%)	258 (56.5%)
Selection
Random	177 (48.0%)	176 (47.4%)	152 (46.6%)	212 (46.4%)
High Risk	192 (52.0%)	195 (52.6%)	174 (53.4%)	245 (53.6%)
Skin color
White	179 (48.5%)	191 (51.5%)	176 (54.0%)	236 (51.6%)
Black	54 (14.6%)	54 (14.6%)	34 (10.4%)	62 (13.6%)
Between white and black (brown)	134 (36.3%)	123 (33.2%)	113 (34.7%)	156 (34.1%)
Indigenous	1 (0.3%)	1 (0.3%)	1 (0.3%)	1 (0.2%)
Asian	1 (0.3%)	2 (0.5%)	2 (0.6%)	2 (0.4%)
¹ n (%)
² Overall N includes participants with DNA methylation data at any timepoint and reflects data from their most recent assessment.

3.2 Wave-Specific Psychiatric Phenotypes

Wave-Specific Psychiatric Phenotypes Prevalence Among Probands with DNA Methylation Data (BHRC)
Psychiatric Phenotype	Wave 0 (N=369)	Wave 1 (N=371)	Wave 2 (N=326)	Lifetime (N=457)¹
ADHD	42 (11.4%)	23 (6.2%)	17 (5.2%)	97 (21.2%)
Anxiety Disorders	29 (7.9%)	48 (12.9%)	40 (12.3%)	163 (35.7%)
Bipolar Disorder or Mania	1 (0.3%)	0 (0.0%)	1 (0.3%)	6 (1.3%)
Eating Disorders	3 (0.8%)	5 (1.3%)	1 (0.3%)	20 (4.4%)
Major Depressive Disorder	11 (3.0%)	37 (10.0%)	52 (16.0%)	123 (26.9%)
OCD	0 (0.0%)	5 (1.3%)	2 (0.6%)	13 (2.8%)
Psychosis	0 (0.0%)	1 (0.3%)	2 (0.6%)	3 (0.7%)
PTSD	5 (1.4%)	3 (0.8%)	6 (1.8%)	30 (6.6%)
Any Psychiatric Disorder	108 (29.3%)	122 (32.9%)	93 (28.5%)	301 (65.9%)
Suicidal Ideation²	0 (0.0%)	0 (0.0%)	0 (0.0%)	161 (35.2%)
Suicide Attempt²	0 (0.0%)	0 (0.0%)	0 (0.0%)	91 (19.9%)
¹ Lifetime N represents the phenotype at any assessment among participants with DNA methylation data.
² Suicidality phenotypes were only evaluated in the last follow-up (Wave 3).
Diagnoses were assessed using the Development and Well-Being Assessment (DAWBA) following DSM-IV criteria. The table summarizes psychiatric disorders identified among probands at each assessment wave.

3.3 Cumulative Psychiatric Phenotypes

Cumulative Psychiatric Phenotypes Prevalence Across Waves Among Probands with DNA Methylation Data (BHRC)
Psychiatric Phenotype	Wave 0 (N=369)	Wave 1 (N=371)	Wave 2 (N=326)	Lifetime (N=457)¹
ADHD	42 (11.4%)	63 (17.0%)	63 (19.3%)	97 (21.2%)
Anxiety Disorders	29 (7.9%)	76 (20.5%)	88 (27.0%)	163 (35.7%)
Bipolar Disorder or Mania	1 (0.3%)	1 (0.3%)	1 (0.3%)	6 (1.3%)
Eating Disorders	3 (0.8%)	9 (2.4%)	8 (2.5%)	20 (4.4%)
Major Depressive Disorder	11 (3.0%)	44 (11.9%)	78 (23.9%)	123 (26.9%)
OCD	0 (0.0%)	6 (1.6%)	9 (2.8%)	13 (2.8%)
Psychosis	0 (0.0%)	1 (0.3%)	3 (0.9%)	3 (0.7%)
PTSD	5 (1.4%)	6 (1.6%)	12 (3.7%)	30 (6.6%)
Any Psychiatric Disorder	108 (29.3%)	182 (49.1%)	189 (58.0%)	301 (65.9%)
Suicidal Ideation²	0 (0.0%)	0 (0.0%)	0 (0.0%)	161 (35.2%)
Suicide Attempt²	0 (0.0%)	0 (0.0%)	0 (0.0%)	91 (19.9%)
¹ Lifetime N represents the phenotype at any assessment among participants with DNA methylation data.
² Suicidality phenotypes were only evaluated in the last follow-up (Wave 3).
Diagnoses were assessed using the Development and Well-Being Assessment (DAWBA) following DSM-IV criteria. The table summarizes lifetime psychiatric disorders identified in probands up to each wave. Phenotypes are counted from the wave of first identification onward.

3.4 Diagnosis Timing Relative to Methylation Acquisition

A diagnosis is counted by acquisition when identified in the same or an earlier wave. Age-18+ diagnoses use p1dawbaage or sdawbaage.

Exclusions

Pre-18-only cases and diagnoses first observed after acquisition are excluded from controls. Participants without an age-18+ evaluation fall outside the adult denominator.

Psychiatric Diagnosis Timing Among Probands with Methylation Data (BHRC)
Cell format: cases / controls / excluded lifetime cases
Psychiatric Phenotype	Lifetime (N=457)	Diagnosed at 18+ (N=441)	By Methylation wave (N=457)	At 18+ by Methylation wave (N=137)
ADHD	97 / 360 / 0	28 / 346 / 67	82 / 360 / 15	9 / 107 / 21
Anxiety Disorders	163 / 294 / 0	96 / 280 / 65	116 / 294 / 47	25 / 78 / 34
Bipolar Disorder or Mania	6 / 451 / 0	4 / 435 / 2	2 / 451 / 4	0 / 134 / 3
Eating Disorders	20 / 437 / 0	10 / 421 / 10	11 / 437 / 9	1 / 134 / 2
Major Depressive Disorder	123 / 334 / 0	75 / 320 / 46	88 / 334 / 35	32 / 83 / 22
OCD	13 / 444 / 0	5 / 428 / 8	10 / 444 / 3	1 / 131 / 5
Psychosis	3 / 454 / 0	2 / 438 / 1	3 / 454 / 0	2 / 134 / 1
PTSD	30 / 427 / 0	17 / 411 / 13	14 / 427 / 16	2 / 127 / 8
Any Psychiatric Disorder	301 / 156 / 0	179 / 147 / 115	248 / 156 / 53	52 / 33 / 52
Cells show cases / controls / excluded cases. Controls were assessed and never positive. Pre-18-only cases are excluded from adult controls; 16 participants lacked an age-18+ evaluation. Diagnoses first observed after the relevant Methylation wave are excluded from acquisition-aligned controls.