Work Package 2:

Genetic risk factors for neuropathic pain


WP2 aims to define genetic variants that influence the development of neuropathic pain with a principal though not exclusive focus on diabetic neuropathy. The specific objectives are:

1) To identify common and low frequency variants that influence the risk and severity of neuropathic pain using genomewide association approaches;

2) To identify rare variants underlying extreme neuropathic pain phenotypes using whole exome sequencing in selected samples, and through targeted resequencing of selected candidate genes in larger numbers;

3) To relate these findings to results emerging from ongoing studies of other microvascular diabetic complications (nephropathy, retinopathy) through integration with data from the SUMMIT consortium.

Description of work

The genetic studies in WP2 will be led by Mark McCarthy (Oxford) and performed in carefully phenotyped cohorts of patients. These include a large cross-sectional cohort of subjects with painful and painless diabetic polyneuropathy and a longitudinal cohort with post-surgical pain. As well as robust classification of disease state, many subjects will have had detailed quantitative assessment of patterns of sensory dysfunction and physiological biomarkers (WPs 4 and 5) that will support more nuanced analyses. Furthermore gene variants associated with increased risk will be studied in terms of molecular pathways and functional analysis in WP3 and be included in the risk prediction algorithm being developed in WP7.

WP leader: University of Oxford