Chris Ponting: Causal variants and mechanisms in complex traits and diseases

Research Programme

1. Pinpointing DNA variants that alter complex disease risk

We seek to determine the causal contribution made by molecular mechanisms to disease susceptibility. First, we infer partially directed gene regulatory networks from single cell RNA-seq data from the same cell type. These graphs use conditional independence to estimate self- and n-point genetic mechanisms (2≤n≤5). Second, DNA variants that alter the expression or activity of genes within a mechanism are then used to test their influence on human traits, using UK Biobank data. This approach is being developed with experts in machine learning (Khamseh), mathematics (Beentjes), and physics (Del Debbio), and with our joint PhD student (Jansma).

2. ME/CFS Genetics

DecodeME is a £3.2m NIHR and MRC-funded strategic grant running until August 2024. With 25,000 intended participants, this is the world’s largest genetic study into ME/CFS. Its first participants were recruited in January 2022, and an initial genome-wide association analysis (using matched UK Biobank individuals as controls) will occur late in 2022. DecodeME is a co-production with people with lived experience of ME/CFS that adheres to UK PPI Standards.

PhD students also work in the group on ME/CFS genetics funded on an integrated studies in Engagement for Impact programme, or by Action for ME and the Chief Scientist Office, or by ME Research UK. We support Action for ME’s vision to establish the UK’s first Genetics Centre of Excellence, a virtual network of ME researchers who, with the ME community, will build on the genetic insights gained through DecodeME and other studies.

Please get in touch (chris.ponting@ed.ac.uk) if you would like to undertake a personal Fellowship, postdoctoral post or studentship with us!