@cathrynlewis introduces the @PGCgenetics showcase event. #WCPG2022 First Pat Sullivan electronically introduces the @PGCgenetics #WCPG2022

I am in the #WCPG2022 IDEA plenary, which discusses the need and approaches to decolonising psychiatric genetics. Panel members are Olivia Matshabane, Paola Giusti-Rodriguez @paolagiustirodriguez, @hailianghuang, and @MeeraPurushott1. Chairs are Lea Davis and John Nurnberger. [I will tweet as much as I can here, but a discussion is always more challenging to tweet]

Next is Omar Shanta who will talk about a GWAS of CNVs in 500k individuals (127k cases, mostly EUR, some AFR). Needed consistent CNV calling across entire cohort. Difficult platforms, which makes things challenging. #WCPG2022 Aims: what is the contribution of rare CNVs, which are those CNVs per disorder, how do rare CNVs compare across disorders? #WCPG2022

I'm back (after a slightly longer lunch) - @juandelahozco is presenting on longitudinal trajectories in the EHR from the Clínica San Juan de Dios, Manizales, Colombia. #WCPG2022 Diagnoses of severe mental illness from ICD10, validated against structured interview and chart review. Some BIP-MDD mismatches (see tweets on @loldeloo talk earlier), but agreement is generally very good, especially for SCZ #WCPG2022

I am in the PUMAS session at #WCPG2022, listening to @b_gelaye talking about the NeuroGAP study NeuroGAP seeks to build collaboration across Africa, particularly across early career researchers. Phenotyping working group has members across Kenya, Uganda, Ethiopia and South Africa, as well as from the Broad. Lots of clinicians, valuable for building phenotypes #WCPG2022

It's day 3, and @sebatlab is outlining the spectrum of genetic influences that affect autism. Clear that although there are strong rare variant effects, these are not monogenic disorders #WCPG2022 Combining together results from common, rare, and structural variants allows a broader picture of genetic risk. See over-transmission of genetic risk at all levels from parents to affected children #WCPG2022

*Runs to bipolar* #WCPG2022 In the bipolar session, @MKoromina discussing fine mapping in bipolar GWAS. #WCPG2022

I'm running between eating disorders and bipolar this afternoon. Starting in eating disorders, where Nadia Micali is introducing the phenotypes. Eating disorders are very underfunded given how frequent and deadly they are #WCPG2022 Today's focus is anorexia nervosa, binge eating disorder, avoidant restrictive food intake disorder. #WCPG2022

Lots of great posters and lunch later, I am now in the methods session for #WCPG2022 (it was a hard decision over depression...) First up is Wouter Peyrot talking about DDx-PRS @caina89 and @hailianghuang introduce WP. DDX-PRS distinguishes between different psychiatric disorders. Early diagnosis is challenging - non specific symptoms often give way to more specific symptoms ten years on - would be valuable to be able to intervene early #WCPG2022

I am in the anxiety session at #WCPG2022 First up is @no_strom presenting on the latest @PGCgenetics GWAS. Introduces the phenotype first - clinically distressing fear/worry Anxiety is under recognised and under treated in primary care - mostly treated by anxiolytics/anti-depressants and psychotherapies. Disorders tend to start in childhood, and are very comorbid with other psych disorders. Multiple risk factors, 30-40% heritability #WCPG2022

Day 2 of #WCPG2022 kicks off as @BFranke_lab introduces another awesome speaker: @kristenbrennand who is going to talk about using stem cells to study the genetics of brain disease. KB starts by nicking @dr_appie's visualisation of the polygenicity of common complex psychiatric disorders #WCPG2022

First session of #WCPG2022 proper! @jorsmo welcomes everyone back to meatspace, before introducing @BFranke_lab, one of the program committee chairs, who in turn will welcome everyone to the conference and it's theme of vanishing boundaries across multiple aspects of the field. BF now introduces Prof Sarah Medland to give the first plenary of #WCPG2022, who will talk about the work of the ENIGMA imaging genetics consortium.

Finally in this session we hear from the @PGCgenetics diversity working groups. First up is the (new!) Consortium for Africa. Numerous African genomics leaders discuss the context and value of the diverse, distinctive human genome in Africa #WCPG2022 Cross-population analyses WG. Working to develop methods. Working with outreach group to highlight (lack of) diversity in psych genomics. Expanding research, grants going in! #WCPG2022

After a brief break for questions, round 2 #wcpg2022 @immaqua describes OCD progress. GWAS ongoing (numerous hits - see symposium on Saturday) and shared with cross disorder efforts. Symptoms analyses yielding publications. Next freeze - diversity and addressing heterogeneity #WCPG2022

It's @PGCgenetics AGM time! Ole Andreassen deputises for Pat Sullivan as the chair #WCPG2022 @PGCgenetics 17 working groups now - meet the work group leaders sessions running across the week #WCPG2022

Apologies to the morning folks in the education session (5am landing and an hour or so walking the streets of Florence required a bit of sleep...)

But I'm only chuffing here! Enjoying listening to @KKuchenbaecker explaining the vanishing boundaries of ancestry #WCPG2022 @KKuchenbaecker KK: Defining specific ancestry groups (e.g. through PCA) can be valuable, but comes with risks of abuse by bad actors. Definitions are not always straightforward and easy to get wrong - relatives have an influence on this (and this also --> misestimates of relatives) #WCPG2022

Finally, Margot Cousin presents on "Impairment of the mitochondrial one-carbon metabolism enzyme SHMT2 causes a novel brain and heart developmental syndrome" #ASHG20 SHMT2 - encodes mitochondrial serine hydroxymethyltransferase 2. Key roles in amino acid metabolism and folic acid pathways, as well as mitochondrial respiration and protein translocation #ASHG20

Next up is Helen Miranda discussing "Increased p4EBP1 underlies ALS pathology associated to P56S mutant VAPB" #ASHG20 ALS is the most common adult-onset neurodegenerative disorder. 50% of patients do not survive beyond third year of diagnosis. Pathophysiology across upper and lower motor neurones. 90% of cases are sporadic in presentation. #ASHG20

Next up is Victor Faundes, who will talk about Impaired eIF5A function causes a craniofacial-neurodevelopmental syndrome that is partially rescued in model systems by spermidine #ASHG20 EIF5A was identified as a candidate developmental disorder gene through WES. Used the DDD resource to identify a further 6 individuals with EIF5A variants, defined a novel syndrome of developmental delay and other features #ASHG20

Slightly late into the fourth plenary: David Blair discussing "Common genetic variants associated with Mendelian disease severity revealed through cryptic phenotype analysis" #ASHG20 Cryptic phenotypes are phenotypes that underlie mendelian diseases, but which are not observed. For some, this will be a liability-threshold model (mendelian as extreme of normal range), but for others it will be a phenotypic outlier model (mendelian as truly separate) #ASHG20

Elise Flynn will end the session, talking about "Transcription factor regulation of genetic variant effects across tissues and individuals" #ASHG20 Genetic variants associated with gene expression = eQTL #ASHG20