A rare coding allele in IFIH1 is protective for psoriatic arthritis

Ashley Budu-Aggrey, John Bowes, Philip E Stuart, Matthew Zawistowski, Lam C Tsoi, Rajan Nair, Deepak Rohit Jadon, Neil McHugh, Eleanor Korendowych, James T Elder, Anne Barton, Soumya Raychaudhuri

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Abstract

OBJECTIVES: 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.

METHODS: 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.

RESULTS: 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.

CONCLUSION: For the first time, we report a rare coding allele in IFIH1 to be protective for PsA. This rare allele has also been identified to have the same direction of effect on type I diabetes and psoriasis. While this association further supports existing evidence for IFIH1 as a causal gene for PsA, mechanistic studies will need to be pursued to confirm that IFIH1 is indeed causal.

Original languageEnglish
Pages (from-to)1321-1324
JournalAnnals of the Rheumatic Diseases
Volume76
Issue number7
Early online date13 May 2017
DOIs
Publication statusPublished - 1 Jul 2017

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Psoriatic Arthritis
Alleles
Medical problems
Genes
Psoriasis
Amino Acids
Meta-Analysis
Proteins
Exome
Type 1 Diabetes Mellitus
Arthritis
Genotype
Direction compound

Keywords

  • Journal Article

Cite this

Budu-Aggrey, A., Bowes, J., Stuart, P. E., Zawistowski, M., Tsoi, L. C., Nair, R., ... Raychaudhuri, S. (2017). A rare coding allele in IFIH1 is protective for psoriatic arthritis. Annals of the Rheumatic Diseases, 76(7), 1321-1324. https://doi.org/10.1136/annrheumdis-2016-210592

A rare coding allele in IFIH1 is protective for psoriatic arthritis. / Budu-Aggrey, Ashley; Bowes, John; Stuart, Philip E; Zawistowski, Matthew; Tsoi, Lam C; Nair, Rajan; Jadon, Deepak Rohit; McHugh, Neil; Korendowych, Eleanor; Elder, James T; Barton, Anne; Raychaudhuri, Soumya.

In: Annals of the Rheumatic Diseases, Vol. 76, No. 7, 01.07.2017, p. 1321-1324.

Research output: Contribution to journalArticle

Budu-Aggrey, A, Bowes, J, Stuart, PE, Zawistowski, M, Tsoi, LC, Nair, R, Jadon, DR, McHugh, N, Korendowych, E, Elder, JT, Barton, A & Raychaudhuri, S 2017, 'A rare coding allele in IFIH1 is protective for psoriatic arthritis', Annals of the Rheumatic Diseases, vol. 76, no. 7, pp. 1321-1324. https://doi.org/10.1136/annrheumdis-2016-210592
Budu-Aggrey A, Bowes J, Stuart PE, Zawistowski M, Tsoi LC, Nair R et al. A rare coding allele in IFIH1 is protective for psoriatic arthritis. Annals of the Rheumatic Diseases. 2017 Jul 1;76(7):1321-1324. https://doi.org/10.1136/annrheumdis-2016-210592
Budu-Aggrey, Ashley ; Bowes, John ; Stuart, Philip E ; Zawistowski, Matthew ; Tsoi, Lam C ; Nair, Rajan ; Jadon, Deepak Rohit ; McHugh, Neil ; Korendowych, Eleanor ; Elder, James T ; Barton, Anne ; Raychaudhuri, Soumya. / A rare coding allele in IFIH1 is protective for psoriatic arthritis. In: Annals of the Rheumatic Diseases. 2017 ; Vol. 76, No. 7. pp. 1321-1324.
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abstract = "OBJECTIVES: 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.METHODS: 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.RESULTS: 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.CONCLUSION: For the first time, we report a rare coding allele in IFIH1 to be protective for PsA. This rare allele has also been identified to have the same direction of effect on type I diabetes and psoriasis. While this association further supports existing evidence for IFIH1 as a causal gene for PsA, mechanistic studies will need to be pursued to confirm that IFIH1 is indeed causal.",
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T1 - A rare coding allele in IFIH1 is protective for psoriatic arthritis

AU - Budu-Aggrey, Ashley

AU - Bowes, John

AU - Stuart, Philip E

AU - Zawistowski, Matthew

AU - Tsoi, Lam C

AU - Nair, Rajan

AU - Jadon, Deepak Rohit

AU - McHugh, Neil

AU - Korendowych, Eleanor

AU - Elder, James T

AU - Barton, Anne

AU - Raychaudhuri, Soumya

N1 - © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

PY - 2017/7/1

Y1 - 2017/7/1

N2 - OBJECTIVES: 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.METHODS: 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.RESULTS: 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.CONCLUSION: For the first time, we report a rare coding allele in IFIH1 to be protective for PsA. This rare allele has also been identified to have the same direction of effect on type I diabetes and psoriasis. While this association further supports existing evidence for IFIH1 as a causal gene for PsA, mechanistic studies will need to be pursued to confirm that IFIH1 is indeed causal.

AB - OBJECTIVES: 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.METHODS: 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.RESULTS: 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.CONCLUSION: For the first time, we report a rare coding allele in IFIH1 to be protective for PsA. This rare allele has also been identified to have the same direction of effect on type I diabetes and psoriasis. While this association further supports existing evidence for IFIH1 as a causal gene for PsA, mechanistic studies will need to be pursued to confirm that IFIH1 is indeed causal.

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M3 - Article

VL - 76

SP - 1321

EP - 1324

JO - Annals of the Rheumatic Diseases

JF - Annals of the Rheumatic Diseases

SN - 0003-4967

IS - 7

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