A genome-wide association study (GWAS) meta-analysis identified genetic correlations and heritability of childhood maltreatment, according to study findings published in Lancet Psychiatry.

Genetic information of 159,124 participants from 4 datasets (UK Biobank [n=143,473], Adolescent Brain Cognitive Development Study [n=5400], Avon Longitudinal Study of Parents and Children [n=8346], and Generation R Study [n=1905]) were combined for this analysis. Childhood maltreatment, defined as emotional or physical neglect or emotional, sexual, or physical abuse, was associated with genetic variants using a linear mixed-effects model.

Study researchers identified a total of 4 operationalizations which had similar heritabilities (H2 range, 0.093±0.019-0.056±0.018; all P >.05) except for severe abuse which had a lower heritability (H2, 0.028±0.018). The operationalizations (r range, 0.47-1.00) and 5 individual maltreatment subtypes (r range, 0.24-1.00) had at least modest genetic correlations.

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GWAS identified a total of 14 loci as significant. These loci accounted for 0.91% of the variance in childhood maltreatment (P =2´10-16) and corresponded with 10% of the heritability (9.3% of total phenotypic variance).

Stratified by prospectively and retrospectively reported maltreatment, results indicated a high genetic correlation between identified variants (r, 0.72; standard error [SE], 0.36; P =.046). Given the high correlation, these data were combined, and 14 loci were identified with a GWAS. Twelve of the lead single nucleotide polymorphisms (SNPs) had directional confirmation in either the retrospective or prospective GWAS and 1 remained significant after Bonferroni correction (rs3851357; P =.0035).

Loci which reached genome-wide significance were associated with mental health conditions (n=6), risky behavior (n=4), smoking and cannabis use (n=3), sleep difficulties (n=2), and reduced intelligence or educational attainment (n=2).

Evidence of gene-by-environment interactions were observed with significant between-family (b, 0.095; SE, 0.007; P <2´10-16) and between-sibling (b, 0.053; SE, 0.02; P =.015) effects.

Using a Mendelian randomization approach, a causal effect on childhood maltreatment was associated with major depressive disorder and a bidirectional association with schizophrenia and attention hyperactivity deficit disorder. No associations between childhood maltreatment and autism, bipolar disorder, type 2 diabetes, coronary artery disease, or C-reactive protein concentration were detected.

This study may have been limited by combining studies which quantified childhood maltreatment using differing methods.

The study authors concluded childhood maltreatment has some heritable component and is complex with underlying genetic and environmental mechanisms.

Disclosure: Multiple authors declared affiliations with the pharmaceutical industry. Please refer to the original article for a full list of disclosures.


Warrier V, Kwong A S F, Luo M, et al. Gene–environment correlations and causal effects of childhood maltreatment on physical and mental health: a genetically informed approach. Lancet Psychiatry. 2021;8(5):373-386. doi:10.1016/S2215-0366(20)30569-1