10/n We @PGCgenetics would like to thank everyone who participated in these (or any) studies for their generosity and time.
We would also like to thank all of our collaborators and funders who made this effort possible –
Excited to share our new Genome-wide meta-analysis of myasthenia gravis! The study identifies novel genetic loci and enhances prediction models. Read more: https://t.co/bfjF5gIKBc @aliceb3000#Genetics#MyastheniaGravis
12/12 These represent what we consider some of the first steps in identifying the ingredients of biological risk for schizophrenia. We hope they provide tools for further study, mechanistic insight and in time better treatments for those with what can be a devastating condition.
11/12 Thanks to the @PGCgenetics for support, the 100s of investigators and researchers in the schizophrenia group, 1000s of clinicians and 10,000s patients who made the study possible.
10/12 A main insight was the convergence of findings between common and rare genetic variation. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants from SCHEMA, highlighting glutamatergic function including GRIN2A and SP4.
9/12 We then priortised 120 genes based on statistical fine-mapping and functional annotation, including 16 genes (and high probability SNPs) with credible causal non-synonymous or untranslated region variation.
7/12 Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Previous enrichments strengthened but we did not see a broadening beyond neuronal cell types.
5/12 Compared to the lowest centile of PRS, the highest has OR for SZ of 39, and 5.6 when the top centile is compared with the remaining 99% of individuals. This should be helpful for research (with caveats https://t.co/ktKAbKC1IX) but not currently for clinical applications.
4/12 SNP-based heritability was estimated to be 0.24, polygenic risk score (PRS) analysis explained a median of 0.073 of variance in liability (SNPs with GWAS P < 0.05).
3/12 Bringing together data from 76,755 individuals with schizophrenia and 243,649 control individuals in mainly European but also East Asian, African American and Latino ancestries identifying, we report common variant associations at 287 distinct genomic loci.
2/12 It was a pleasure to work on this with all colleagues from the PGC including Vasa Trubetskoy @AFPopgen@stephanripke and Mick O'Donovan and alongside the SCHEMA consortium @TarjS@dalygene @bmneale
1/12 Very pleased to finally share the @PGC Schizophrenia Group paper: Mapping genomic loci implicates genes and synaptic biology in schizophrenia https://t.co/IEcUWZVQiF (my first proper thread!!)
What is the role of genetics in schizophrenia? Thanks to an international collaboration and the largest-ever genetic study on the disorder, researchers from #CharitéBerlin have brought us one step closer to an answer. @nature@bridges_berlin https://t.co/trnSrqbnZV
2/2 Für weitere Informationen zu #Genetik und #Psychiatrie: Der leitende Studienautor Prof. Ripke von der #CharitéBerlin sprach im @Dlf_Forschung u. a. über Schizophrenie-Gene und genetisch ähnliche Muster von verschiedenen psychiatrischen Krankheiten. https://t.co/rJ54Qo1BZV
1/2 Welche Rolle spielt das Erbgut bei #Schizophrenie? Forschende der #CharitéBerlin sind der Antwort ein Stück nähergekommen. In internationaler Zusammenarbeit ist die bisher größte genetische Studie dazu entstanden. @nature@bridges_berlin https://t.co/ZpKOcg3fud