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Gene-environment interaction — MRCPsych Paper A MCQ

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HardGeneticsGene-environment interactionMRCPsych Paper A

A prospective cohort examines schizophrenia polygenic risk and regular high-potency cannabis use. Each is independently associated with psychotic disorder. However, among participants with both high polygenic risk and regular cannabis exposure, the observed incidence exceeds that expected by adding the separate excess incidences associated with each factor. Schizophrenia polygenic risk does not predict whether participants use cannabis. Which genetic epidemiological mechanism best explains this finding?

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Correct answer: B — Gene–environment interaction

The answer is B, gene–environment interaction. The effect of cannabis on psychosis risk differs according to genetic liability: their joint excess risk is greater than expected from adding their separate effects, demonstrating positive interaction on an additive scale. Gene–environment correlation would mean that genetic liability influences the likelihood of cannabis exposure; the stem explicitly excludes this. Incomplete penetrance describes failure of a susceptibility genotype to produce the phenotype in every carrier, but does not itself establish a differential environmental effect. Population stratification is confounding caused by ancestry-related differences in allele and outcome frequencies. Genetic drift is random change in population allele frequencies and cannot explain the individual-level joint effect.

Reference: Guloksuz S et al. Examining the independent and joint effects of molecular genetic liability and environmental exposures in schizophrenia: results from the EUGEI study. World Psychiatry. 2019;18(2):173–182. https://pubmed.ncbi.nlm.nih.gov/31059627/