Psychiatric genetics and epigenetics — structured clinical viva

Slide 1 — heritabilities. Schizophrenia shows high twin heritability (~80% classically from meta-analysis); major depression moderate (~37% meta-analytic twin estimate); bipolar high with genetic links to unipolar depression dimensions.^[1][2] Immediately state: heritability is population variance partition; incomplete MZ concordance; environment remains causal and interventional.

Slide 2 — Manhattan/GWAS. Points to polygenic common-variant architecture. Name PGC 2014 108 loci and later expanded maps prioritising synaptic biology; depression GWAS similarly polygenic at scale.^[3][4][5] Mention cross-disorder pleiotropy as explanation for comorbidity genetics.^[10] Missing heritability bridges to rare variants/CNVs and imperfect tagging.

Slide 3 — 22q11. Prototype high-impact CNV with multisystem developmental medicine and elevated psychosis risk; management is multidisciplinary, not genetics-only.^[6][7]

Epigenetics follow-up. Meaney/Weaver maternal care → GR promoter methylation paradigm illustrates environmental embedding of gene expression; do not claim a clinical methylation diagnostic for human depression on the ward.^[8]

PRS/ethics follow-up. Research tool, limited discrimination, ancestry caveats; non-directive counselling; refuse genetic essentialism.^[9]