Psychiatric genetics and epigenetics

Meet the paper

In July 2014 the Schizophrenia Working Group of the Psychiatric Genomics Consortium published a single paper in Nature that is the line where psychiatric genetics grew up: 108 genome-wide significant loci for schizophrenia, across roughly 37,000 cases and 113,000 controls, with biological signals pointing at synaptic genes and the immune or MHC region.^[5]

What changed was not the clinic — it was the exam question. Before 2014, registrars could answer "schizophrenia is heritable but we have not found the genes." After 2014 the honest answer became "highly polygenic, many loci of small effect, no single causative gene, and a polygenic score that is a research tool rather than a clinic test."^[5][17]

This topic teaches that architecture: what twin studies and GWAS actually show, what 22q11.2 deletion means at the bedside, and where genomics changes a formulation without changing first-line treatment.^[1][13]

References17ShowHide

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3. [3]Sullivan PF, Neale MC, Kendler KS Genetic epidemiology of major depression: review and meta-analysis Am J Psychiatry, 2000.PMID 11007705
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5. [5]Schizophrenia Working Group of the Psychiatric Genomics Consortium Biological insights from 108 schizophrenia-associated genetic loci Nature, 2014.PMID 25056061
6. [6]Trubetskoy V, Pardiñas AF, Qi T, et al. Mapping genomic loci implicates genes and synaptic biology in schizophrenia Nature, 2022.PMID 35396580
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12. [12]Marshall CR, Howrigan DP, Merico D, et al. Contribution of copy number variants to schizophrenia from a genome-wide study of 41,321 subjects Nat Genet, 2017.PMID 27869829
13. [13]Bassett AS, McDonald-McGinn DM, Devriendt K, et al. Practical guidelines for managing patients with 22q11.2 deletion syndrome J Pediatr, 2011.PMID 21570089
14. [14]McDonald-McGinn DM, Sullivan KE, Marino B, et al. 22q11.2 deletion syndrome Nat Rev Dis Primers, 2015.PMID 27189754
15. [15]Singh T, Poterba T, Curtis D, et al. Rare coding variants in ten genes confer substantial risk for schizophrenia Nature, 2022.PMID 35396579
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