A rare coding allele in IFIH1 is protective for psoriatic arthritis

Annals of the Rheumatic Diseases
Ashley Budu-AggreySoumya Raychaudhuri

Abstract

Psoriatic arthritis (PsA) is an inflammatory arthritis associated with psoriasis. While many common risk alleles have been reported for association with PsA as well as psoriasis, few rare coding alleles have yet been identified. To identify rare coding variation associated with PsA risk or protection, we genotyped 41 267 variants with the exome chip and investigated association within an initial cohort of 1980 PsA cases and 5913 controls. Genotype data for an independent cohort of 2234 PsA cases and 5708 controls was also made available, allowing for a meta-analysis to be performed with the discovery dataset. We identified an association with the rare variant rs35667974 (p=2.39x10-6, OR=0.47), encoding an Ile923Val amino acid change in the IFIH1 gene protein product. The association was reproduced in our independent cohort, which reached a high level of significance on meta-analysis with the discovery and replication datasets (p=4.67x10-10). We identified a strong association with IFIH1 when performing multiple-variant analysis (p=6.77x10-6), and found evidence of independent effects between the rare allele and the common PsA variant at the same locus. For the first time, we report a rare coding allele in IFIH1 to be protective...Continue Reading

References

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Citations

Feb 10, 2018·International Journal of Molecular Sciences·Marie-Astrid BoutetCostantino Pitzalis
Aug 8, 2020·International Journal of Rheumatic Diseases·Jingjing ChenYahua Wang
Jun 9, 2020·Frontiers in Immunology·Shaoling ZhengTianwang Li
Mar 14, 2021·Seminars in Immunopathology·Sara RahmatiVinod Chandran
May 23, 2021·Best Practice & Research. Clinical Rheumatology·Darren D O'Rielly, Proton Rahman

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Methods Mentioned

BETA
chip
genotyping
exome sequencing

Software Mentioned

R
GenomeStudio Data Analysis
EIGENSOFT
SKAT
PLINK

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