Thread by @Joni_Coleman

@cathrynlewis introduces the @PGCgenetics showcase event. #WCPG2022

First Pat Sullivan electronically introduces the @PGCgenetics #WCPG2022

PGC 1000+ scientists from 50+ countries. Primary funding from NIH, but many others as well. 8 sites, 16 PIs in USA, UK, and Ireland. Coordinating committee including regional representatives. #WCPG2022

Executive committee of PS, @cathrynlewis , Arpana Agrawal, Ole Andreassen #WCPG2022

Aims: genetic discovery for severe psych disorders, especially increasing ancestry diversity, advance discovery, going beyond standard diagnosis, and expanding understanding of treatment #WCPG2022

PGC under covered in the tropics, working to improve #WCPG2022

How to get involved? Sign MoU. Bring in data, or partner with existing PI to conduct secondary data. Matchmaking between people with samples and people who can genotype them. Talk to group leaders! #WCPG2022

New study - Common variant genotype+ CNVS + WES on 130k cases. Focussed on SCZ, BIP1, MDD severe. Free assays, data comes back, but working with for-profit #WCPG2022 Contact [psych dot exome at gmail dot com] if interested.

Lea Davis now talks about data access and data intake. #WCPG2022

Data intake pipeline: welcome. See pgc.unc.edu. Mostly comes through workgroup leaders. Once contact is established, intake through the data receiving committee #WCPG2022

DRC members liaise with new and existing members to vet incoming data and ensure contact with Stage 1 analyst. #WCPG2022

Data owner submits enquiry form, 5 mins, basic info, found on @PGCgenetics website. Gathers important metadata to ensure data intake can proceed without concern #WCPG2022

Fuller data information form filled out - allows methods data for paper to be gathered and associated with the data from the start. Reviewed by DRC rep. Email to data owner with LISA upload instructions #WCPG2022

Data to LISA, stage 1 analyst QC and harmonises. --> Stage 2 analysis (working group analysts) #WCPG2022

Data access - DAC committee. Not an approval body (work groups deal with that, cohort PIs as needed), DAC facilitates data access. #WCPG2022

DRC and DAC reps are volunteers, don't be mean to them #WCPG2022

Data access is increasingly challenging due to regulations #WCPG2022

376 currently active secondary data access requests. Secondary access works by proposal and approval of request to/by work group. Data access approved and access granted to data on LISA. Individual level data can never leave LISA! #WCPG2022

More info on data access can be found on the @PGCgenetics website. #WCPG2022

There is a PGC data bundle on dbGAP - makes life a lot easier...! #WCPG2022

Various back end initiatives underway as well as new secondary phenotyping effort #WCPG2022

Now Jerry Guintivano talks about @PGCgenetics postpartum depression GWAS. #WCPG2022

PGC successes - ID of 100s of loci implicated in psych, well-defined and vetted analytical pipelines, opportunity to reduce heterogeneity and define specific subphenotypes. PPD is an example - 10-15% prevalence, has rapidly increased under COVID. #WCPG2022

PPD is morbid across the family unit and is often missed, not uniformly screened for #WCPG2022

PPD: more homogeneous than MDD and twin studies suggest it is more heritable. Challenges too: defining period, establishing depression status, need for specific exposure - women not routinely screened, need MDD data to be intersected with pregnancy to use it #WCPG2022

GWAS - 20 cohorts, 18k cases 58k controls. EUR meta-analysis and trans-ancestry analysis. No GWS hits, but suggestive hits are enriched in brain, neuroendocrine and reproductive tissue eQTLs #WCPG2022

PPD correlated with MDD rg not distinguishable from 1. Broad rg with other psych disorders, and with PCOS. #WCPG2022

Some tentative results from cell types, but very preliminary #WCPG2022

Finally @Juditperala will talk about using @PGCgenetics studies to evaluate pathway polygenic risk scores #WCPG2022

PRS can be a useful tool for stratified medicine, not there yet in psych. Typically work in a polygenic paradigm , but psych disorders are very complex, do perhaps a pathway polygenic paradigm promotes prediction? #WCPG2022

Enter PRSet, a variant of PRSice. Pathway polygenic scores enable decomposition of genetic risk. #WCPG2022

Work in UK Biobank to separate Crohn's disease from ulcerative colitis - underpowered, couldn't separate with enough precision #WCPG2022

Can compare artificial compound diseases by meta analysing distinct diseases and then splitting them apart again - works, but is artificial #WCPG2022

Enter @PGCgenetics bipolar disorder - natural BIP1 Vs BIP2 distinction. Able to separate with pathway prediction scores, albeit with low R2 #WCPG2022

Further directions - incorporate functional genomics, improve pathways in the dataset #WCPG2022