Family-based integrative approaches to elucidate the genetic architecture of spondyloarthritis

Spondyloarthritis (SpA) is a common chronic inflammatory rheumatic disease with a strong genetic component. More than 40 susceptibility loci have been uncovered but they explain only a small fraction of disease predisposition. Some of the missing heredity probably lies in rare variants with large effects and family-based designs might help to identify them. Study of a large set of multiplex families from the French genetic group of SpA led to the identification of a chromosomal region showing significantly linked with SpA on 13q13. Analysis of the ultra-deep sequencing of this region is underway. Context-specific gene expression and epigenetic processes are also useful to better understand SpA genetic architecture. Study of gene expression in monocyte-derived dendritic cells from SpA patients and their unaffected siblings has highlighted an unexpected dysregulated pathway: lipid metabolism regulation. It also revealed that SpA-associated ERAP1 haplotypes influence gene expression.
Félicie Costantino, MD, PhD, is Assistant Professor in the Rheumatology Department of Ambroise Paré University Hospital (Boulogne-Billancourt, France) headed by Prof. Maxime Breban. She obtained a PhD in Genetics from Paris-Descartes University in 2013 and works in the INSERM UMR 1173 “Infection and Inflammation” Research Unit led by Prof. Gilles Chiocchia at Versailles-Saint-Quentin University. Her research interest is focused on SpA and her main goal is to identify the genetic determinants of the disease by combining genetic and functional genomic studies in family context.
Key publications – A family-based genome-wide association study reveals an association of spondyloarthritis with MAPK14. Costantino F. et al (2017) Ann Rheum Dis, 75:310-314. – Whole-genome single nucleotide polymorphism-based linkage analysis in spondyloarthritis multiplex families reveals a new susceptibility locus in 13q13. Costantino F. et al (2016) Ann Rheum Dis, 75, 1380-1385. – ERAP1 gene expression is influenced by non-synonymous polymorphisms associated with predisposition to spondyloarthritis. Costantino F. et al (2015) Arthritis Rheumatol, 67, 1525-1534.