Along with her team, Dr. Patricia Silveira, a researcher at the Douglas Research Centre and Associate Professor at McGill University’s Department of Psychiatry, has just published an article investigating gene variants associated with common diseases, considering the effects of emotional abuse and neglect.
KEY TAKE-AWAYS
This study asked whether the genetic variants that increase risk for common adult diseases are the same variants that influence how people respond to adverse childhood experiences. Using data from 180,129 UK Biobank participants, researchers compared genome-wide association studies (GWAS) with genome-wide environment interaction studies (GWEIS) focused on childhood emotional abuse and neglect.
The main finding was that the genetic factors linked to disease risk were largely different from those associated with vulnerability to early-life adversity. Across cardiovascular disease, type 2 diabetes, mood disorders, and neurotic disorders, there was virtually no overlap between the genetic signals identified by GWAS and GWEIS.
WHY THIS MATTERS
Many genetic prediction tools, including polygenic risk scores, are based on GWAS findings and assume that the same genetic variants driving disease risk also shape responses to environmental adversity.
This study suggests otherwise. Genetic susceptibility to disease and genetic sensitivity to early-life experiences may involve different biological pathways. As a result, GWAS-based models alone may provide only a partial view of disease risk, especially for conditions influenced by environmental factors.
WHAT THEY DID
Dr. Silvera and her team analyzed genetic and health data from 180,129 UK Biobank participants, including 22,372 who reported childhood emotional adversity, such as feeling hated or unloved.
They examined four outcomes: cardiovascular disease, type 2 diabetes, mood disorders, and neurotic disorders. GWAS was used to identify variants associated with disease risk, while GWEIS tested whether genetic variants altered the impact of childhood adversity on later disease development. Both analyses were conducted in the same population using the same analytical framework.
WHAT THEY FOUND
GWAS identified significant genetic associations for cardiovascular disease and type 2 diabetes, but not for mood or neurotic disorders. No GWEIS variants reached genome-wide significance.
Crucially, variants linked to adversity-related effects were located outside the significant GWAS regions. Even at more relaxed thresholds, no overlap was observed between GWAS and GWEIS findings at either the SNP or gene level. Heritability was evident for disease risk, particularly for physical disorders, but not for gene-environment interaction effects, suggesting these effects are highly context dependent.
WHAT IT MEANS
Genes associated with disease risk are not necessarily the same genes that influence responses to childhood adversity. Gene-environment interactions may act through pathways related to environmental sensitivity rather than baseline disease risk.
WHAT’S NEXT
Larger studies and more powerful methods will be needed to detect subtle gene-environment interactions. Integrating environmental exposures with functional genomics and biological pathway analyses may provide a more complete understanding of disease development and support more personalized approaches to prevention and treatment.
