A genome-wide association study (GWAS) meta-analysis identified genetic correlations and the heritability of abuse in children, according to the results of the study published in Lancet Psychiatry.
Genetic information from 159,124 participants from 4 data sets (UK Biobank [n=143,473], Study of the cognitive development of the brain in adolescents [n=5400], Avon Longitudinal Study of Parents and Children [n=8346], and Generation R study [n=1905]) were combined for this analysis. Child abuse, defined as emotional or physical neglect or emotional, sexual or physical abuse, has been linked to genetic variants using a linear mixed effects model.
The study researchers identified a total of 4 operationalizations with similar heritabilities (H2 range, 0.093 ± 0.019-0.056 ± 0.018; all P> 0.05) with the exception of severe abuse, which had a lower heritability (H2, 0.028 ± 0.018). The operationalizations (R range 0.47-1.00) and 5 individual abuse subtypes (r range 0.24-1.00) showed 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 child abuse (P = 2´10-16) and corresponded to 10% of the heritability (9.3% of the total phenotypic variance).
Stratified according to prospectively and retrospectively reported abuse, the results showed a high genetic correlation between the identified variants (r, 0.72; standard error [SE], 0.36; P = .046). Due to the high correlation, these data were combined and 14 loci were identified with a GWAS. Twelve of the leading single nucleotide polymorphisms (SNPs) had directional confirmation in either retrospective or prospective GWAS and 1 remained significant after Bonferroni correction (rs3851357; P = 0.0035).
Loci that achieved genome-wide significance were associated with mental illness (n = 6), risky behavior (n = 4), smoking and cannabis use (n = 3), sleep disorders (n = 2), and decreased intelligence or education (n = 2).
Indications of gene-environment interactions were observed with significant intermediate families (b, 0.095; SE, 0.007; P <2´10-16) and between siblings (b, 0.053; SE, 0.02; P = .015). Effects.
Using a Mendelian randomization approach, a causal effect on childhood abuse was associated with major depression and a bidirectional association with schizophrenia and attention deficit hyperactivity deficit disorder. No associations were found between child abuse and autism, bipolar disorder, type 2 diabetes, coronary artery disease, or C-reactive protein levels.
This study may have been limited by the combination of studies quantifying child abuse by different methods.
The study’s authors concluded that childhood abuse has a hereditary component and is complex with underlying genetic and environmental mechanisms.
Disclosure: Several authors stated links to the pharmaceutical industry. For a full list of the details, see the original article.
reference
Warrier V, Kwong ASF, Luo M, et al. Gene-Environment Correlations and the causal effects of child abuse on physical and mental health: a genetically informed approach. Lancet psychiatry. 2021; 8 (5): 373-386. doi: 10.1016 / S2215-0366 (20) 30569-1
