Table 2.
Summary of Population Studies
| Study | Sample; Number of Participants | Childhood Adversity Investigated | Gene-Environment Correlation Between SZ PRS and CA | SZ PRS GWAS | Gene-Environment Interaction Between SZ PRS, CA, and Psychosis |
|---|---|---|---|---|---|
| Docherty et al (2018)45 | S4S; 5947 | Interpersonal trauma | q-value < 0.01a; effect size not reportedb | PGC2 (2014) | Not assessed |
| Krapohl et al (2017)53 | TEDS; 6710 | Parental smacking | β = .010, SE = 0.013, X 2 = 0.55, P = 5E-01 | PGC2 (2014) | Not assessed |
| Lehto et al (2020)55 | UKBB; 3151 adopted | Adoption | OR = 1.05; 95% CI = 1.01, 1.09; P = .01 a | PGC2 (2014) | Not assessed |
| Leppert et al (2020)52 | UKBB; 334 976 (total) | Sexually molested, felt loved, physically abused by family, felt hated by family, and someone to take to doctor |
Sexually molested: β = .062; 95% CI = 0.040, 0.084; P = 3.11E-08
a
Felt loved: β = −.044; 95% CI = −0.055, −0.032; P = 3.52E-14a Physically abused by family: β = .033; 95% CI = 0.017, 0.048; P = 3.91E-05 Felt hated by family: β = .060; 95% CI = 0.043, 0.077; P = 3.24E-12a Someone to take to doctor: β = −.042; 95% CI = −0.058, −0.025; P = 6.36E-07a |
PGC2 (2014) | Not assessed |
| Pergola et al (2019)24 | TRAILS; 650 | Bullying victimization | Time point 1: N = 650, all P > .05c Time point 2: N = 625, F2,611 = 3.4, P = .033, partial η 2 = 0.011 (ANOVA)a,c |
PGC2 (2014) | Not assessed |
| Pries et al (2020)46 | TwinssCan; 593 | General adversity | β = −.01; 95% CI = −0.03, 0.02; P = .676 | PGC2 + CLOZUK (2018) | Not assessed |
| Riglin et al (2019)49 | ALSPAC; 8365 | Peer victimization | OR = 0.95; 95% CI = 0.86, 1.04; P = .292 | PGC2 (2014) | Not assessed |
| Sallis et al (2020)42 | ALSPAC; 7426 (child PRS) MoBa; 7244 (child PRS) |
Bullying, domestic violence, sexual abuse, emotional neglect, emotional cruelty, and physical cruelty |
ALSPAC any adversity across childhood and adolescence: OR = 1.14; 95% CI = 1.08, 1.20; P = 8.4E-6 Bullying: OR = 1.03; 95% CI = 0.97, 1.09; P = .342 Domestic violence: OR = 1.07; 95% CI = 1.01, 1.13; P = .028a Sexual abuse: OR = 1.15; 95% CI = 1.03, 1.29; P = .012a Emotional neglect: OR = 1.06; 95% CI = 0.96, 1.17; P = .235 Emotional cruelty: OR = 1.16; 95% CI = 1.09, 1.24; P = 3.49E-6a Physical cruelty: OR = 1.12; 95% CI = 1.05, 1.20; P = 7.9E-4a MoBa: OR = 1.08; 95% CI = 1.02, 1.14; P = .005 |
PGC2 (2014) | Not assessed |
| Schoeler et al (2019)50 | ALSPAC; 5028 | Bullying | β = .038; 95% CI = 0.008, 0.068; P = .02 a | PGC2 + CLOZUK (2018) | Not assessed |
| Ratanatharathorn et al (2021)54 | NHS2; 13 313 | Physical/emotional abuse, physical assault, and sexual abuse |
Physical/emotional abuse: OR = 1.11; 95% CI = 1.07, 1.16; P = 2.10E-08
a
Physical assault: OR = 1.09; 95% CI = 1.04, 1.13, P = 2.50E-05a Sexual abuse: OR = 1.02, 95% CI = 0.98, 1.07, P = 2.80E-01 |
PGC2 (2014) | Not assessed |
| Bolhuis et al (2021)44 | Generation R; 1901 | General adversity |
P
t
< .5: OR = 1.08; 95% CI = 1.02,1 .15; P = .01 (Generation R)a Pt < .5: OR = 1.02; 95% CI = 1.01, 1.03; P = .001 (ALSPAC)a |
PGC2 (2014) | Not assessed |
| Peel et al (2021)43 | TEDS; 3963 | Emotional and physical abuse | β = .44; 95% CI = 0.13, 0.75; P = .01 a | PGC2 + CLOZUK (2018) | Not assessed |
| Results from controls in clinical population studies | |||||
| Trotta et al (2016)48 | GAP; 110 unaffected community controls | General adversity Physical/sexual abuse, parental separation, parental death, taken into the care system, and number of family arrangements | Controls: OR = 2.77; 95% CI = −1.92, 7.47; P = .247 | PGC2 (2014) | Assessed in cases |
| Aas et al (2021)47 | EU-GEI; 690 controls | General adversity | Control: β = .03; 95% CI = −0.09, 0.25; P = .34 (binary) Control: β = .09; 95% CI = 0.02, 0.16; P = .02a (continuous) |
PGC2 (2014) | Assessed in cases |
| Guloksuz et al (2019)58 | EU-GEI; 1542 controls | Bullying, emotional neglect, physical neglect, emotional abuse, physical abuse, and sexual abuse |
Bullying: OR = 1.28; 95% CI = 0.87, 1.89; P = .21 Emotional abuse: OR = 1.13; 95% CI = 0.81, 1.59; P = .476 Physical abuse: OR = 1.84; 95% CI = 1.19, 2.84; P = .006a Sexual abuse: OR = 0.79; 95% CI = 0.51, 1.23; P = .292 Emotional neglect: OR = 1.16; 95% CI = 0.90, 1.50; P = .258 Physical neglect: OR = 1.19; 95% CI = 0.90, 1.58; P = .219 |
PGC2 (2014) | Assessed in cases |
Note: ALSPAC, Avon Longitudinal Study of Parents and Children; CA, childhood adversity; EU-GEI, EUropean Network of National Schizophrenia Networks Studying Gene-Environment Interactions; GAP, genes and psychosis; GWAS, genome-wide association studies; MoBa, Norwegian Mother, Father and Child Cohort Study; NHS2, Nurses’ Health Study 2; PGC2, Psychiatric Genomics Consortium 24; PGC + CLOZUK, Psychiatric Genomics Consortium and CLOZUK3; SZ PRS, schizophrenia polygenic risk score; S4S, spit for science; TEDS, Twins Early Development Study; TRAILS, TRacking Adolescents’ Individual Lives Survey; TwinssCan, East Flanders Prospective Twin Survey; UKBB, UK BioBank. The table describes the population studies included in this review and outlines the number of participants with genetic data, the type of childhood adversity investigated, and the outcome.
aStudy defined statistical significance. Effect sizes reported in bold were used in the meta-analysis.
bStudy not included in meta-analysis due to no effect size.
cStudy not included in meta-analysis because not peer reviewed.