Psych Vivas · Foundations — psychiatric genetics and epigenetics
Psychiatric genetics and epigenetics — structured clinical viva
Fellowship viva on heritability, GWAS architecture, CNVs/22q11, PRS limits, epigenetics, and counselling ethics.
On this page & tools
Target exams
Interpretation
Reveal interpretation
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]
Key points
References
- [1]Sullivan PF, Kendler KS, Neale MC Schizophrenia as a complex trait: evidence from a meta-analysis of twin studies Arch Gen Psychiatry, 2003.PMID 14662550
- [2]Sullivan PF, Neale MC, Kendler KS Genetic epidemiology of major depression: review and meta-analysis Am J Psychiatry, 2000.PMID 11007705
- [3]Schizophrenia Working Group of the Psychiatric Genomics Consortium Biological insights from 108 schizophrenia-associated genetic loci Nature, 2014.PMID 25056061
- [4]Trubetskoy V, Pardiñas AF, Qi T, et al. Mapping genomic loci implicates genes and synaptic biology in schizophrenia Nature, 2022.PMID 35396580
- [5]Wray NR, Ripke S, Mattheisen M, et al. Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression Nat Genet, 2018.PMID 29700475
- [6]Malhotra D, Sebat J CNVs: harbingers of a rare variant revolution in psychiatric genetics Cell, 2012.PMID 22424231
- [7]McDonald-McGinn DM, Sullivan KE, Marino B, et al. 22q11.2 deletion syndrome Nat Rev Dis Primers, 2015.PMID 27189754
- [8]Weaver ICG, Cervoni N, Champagne FA, et al. Epigenetic programming by maternal behavior Nat Neurosci, 2004.PMID 15220929
- [9]Lewis CM, Vassos E Polygenic risk scores: from research tools to clinical instruments Genome Med, 2020.PMID 32423490
- [10]Cross-Disorder Group of the Psychiatric Genomics Consortium Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders Cell, 2019.PMID 31835028