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Polygenic Scores and Environmental Factors in Psychiatric Disorders: Gene-Environment Interaction Analyses Using the

Tahereh Gholipourshahraki1,2, Linda Ejlskov1, Birgitte Semark1

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Genetic and environmental factors influence psychiatric disorder risk. This study found limited, modest gene-environment interactions, highlighting the need for larger studies to understand complex genetic and environmental influences on mental health.

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Area of Science:

  • Psychiatry and Genetics
  • Environmental Epidemiology

Background:

  • Psychiatric disorders have complex origins involving genetic and environmental factors.
  • The interplay between genetic predisposition and environmental exposures in psychiatric disorder risk is not well understood.
  • Polygenic scores (PGS) serve as a proxy for genetic risk in psychiatric research.

Purpose of the Study:

  • To investigate the interaction between polygenic scores (PGS) and environmental factors in the risk of psychiatric disorders.
  • To examine how genetic liability, as measured by PGS, interacts with various environmental factors across different psychiatric conditions.
  • To identify specific gene-environment interactions that may contribute to the etiology of psychiatric disorders.

Main Methods:

  • Utilized the iPSYCH case-cohort sample (n=141,265) from Danish nationwide registers.
  • Assessed environmental factors including region, urbanicity, parental socioeconomic status, parental age, parental psychiatric history, and early-life exposures.
  • Employed logistic regression to analyze the effects of PGS, environmental factors, and their interactions on psychiatric disorders, adjusting for covariates.

Main Results:

  • Both polygenic scores (PGS) and environmental factors were significantly associated with psychiatric disorder risk.
  • Limited evidence of statistically significant gene-environment interactions was found across most psychiatric disorders studied.
  • Specific significant interactions included associations between PGS and region for ADHD, parental income for bipolar disorder, parental psychiatric history for major depressive disorder, paternal age for schizophrenia, and region for anorexia nervosa.

Conclusions:

  • Polygenic scores (PGS) for psychiatric disorders are associated with risk across diverse environmental contexts.
  • Detected gene-environment interactions were modest and specific to certain mental disorders, indicating the complexity of their interplay.
  • The findings underscore the challenges in detecting robust gene-environment interactions and emphasize the need for large-scale studies with sufficient statistical power to elucidate subtle effects in psychiatric disorder etiology.