Skilgreining áhættuþátta fyrir sjálfsofnæmissjúkdóma - verkefni lokið
Fréttatilkynning verkefnisstjóra
The aim of the project was to examine, in a comprehensive manner, the relationship between sequence variants in the human genome and the risk of autoimmune and inflammatory diseases.
Heiti verkefnis: Skilgreining
áhættuþátta fyrir sjálfsofnæmissjúkdóma
Verkefnisstjóri: Snævar Sigurðsson, Íslenskri erfðagreiningu
Tegund styrks: Rannsóknastöðustyrkur
Styrktímabil: 2012-2014
Fjárhæð styrks: 19,32 millj. kr. alls
Tilvísunarnúmer Rannís: 120458
Whole genome SNP typing and whole genome sequencing (WGS) of large proportion of Icelanders at deCODE created a valuable resource enabling investigations of the association of not only common sequence variants but also rare variants with high impact on disease risks.
No genome wide significant associations of novel
sequence variants with the autoimmune disease were found, but several sequence
variants showing suggestive associations were followed up in external cohorts,
but did not reach genome wide significant association in Icelandic and
replication sample sets combined. We calculated polygenic risk scores (PRS)
based on publicly available summary statistics for common autoimmune diseases,
quantified genetic overlap between the autoimmune diseases in Icelanders and showed
that RA can be characterized by autoantibody presence or absence.
We identified three loci that associate with the risk of the diverticular
disease, representing a non-autoimmune inflammatory disease of the
gastrointestinal tract, in Iceland and replicated the association in a follow
up cohort from Denmark. These are the first genome wide significant
associations reported for this disease. The discoveries of sequence variants
affecting the risk of complex diseases will help us understand the underlying
cause of the diseases, hopefully increase available treatments and make better
diagnostics possible. The results from the association analysis have been
submitted to a high impact peer reviewed journal.
(Sigurdsson et al. Submitted: Sequence
variants in ARHGAP15, COLQ and FAM155A associate with diverticular disease and diverticulitis) and
(Olofsson et al. Submitted: Meta-analysis informed by genetic
correlations yields novel Multiple sclerosis sequence variants).
