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Association of Gout Polygenic Risk Score with Age at Disease Onset and Tophaceous Disease in European and Polynesian Men with Gout.

Association of Gout Polygenic Risk Score with Age at Disease Onset and Tophaceous Disease in European and Polynesian Men with Gout. Thumbnail


Abstract

OBJECTIVE: To determine whether a gout polygenic risk score (PRS) associates with age at gout onset and tophaceous disease in European (EUR), East Polynesian (EP), and West Polynesian (WP) men/women with gout.

METHODS: A 19-variant gout PRS was produced in seven European gout cohorts (NTOTAL =?4,016), two East Polynesian gout cohorts (NTOTAL =?682), and one West Polynesian gout cohort (N = 490). Sex-stratified regression models were used to estimate the relationship between the PRS and age at onset/tophaceous disease.

RESULTS: The PRS associated with earlier age at gout onset in men (ßEUR [95%-CI]: -3.61 [-4.32, -2.90] years per unit PRS; ßEP : -6.35 [-8.91, -3.80]; ßWP : -3.51 [-5.46, -1.57]) but not in women (ßEUR : 0.07 [-2.32, 2.45]; ßEP : 0.20 [-7.21, 7.62]; ßWP : -3.33 [-9.28, 2.62]). The PRS showed a positive association with tophaceous disease in men (OREUR : 1.15 [1.00, 1.31]; OREP : 2.60 [1.66, 4.06]; ORWP : 1.53 [1.07, 2.19]) but not in women (OREUR : 0.68 [0.42, 1.10]; OREP : 1.45 [0.39, 5.36]). The age at onset association was robust to the removal of ABCG2 variants from the PRS in Europeans and East Polynesians but not West Polynesians (ßEUR : -2.42 [-3.37, -1.46]; ßEP : -6.80 [-10.06, -3.55]; ßWP : -1.79 [-4.74, 1.16]).

CONCLUSION: Gout risk variants also harbor risk for earlier age at onset and tophaceous disease in European and Polynesian men. Our findings suggest that earlier gout onset involves the accumulation of gout risk alleles in men but perhaps not women, and that this genetic risk is shared across multiple ancestral groups.

Citation

Roddy, E. (2022). Association of Gout Polygenic Risk Score with Age at Disease Onset and Tophaceous Disease in European and Polynesian Men with Gout. Arthritis and Rheumatology, 75(5), 816-825. https://doi.org/10.1002/art.42393

Acceptance Date Oct 2, 2022
Online Publication Date Apr 26, 2023
Publication Date Oct 25, 2022
Publicly Available Date Oct 26, 2023
Journal Arthritis & Rheumatology
Print ISSN 2326-5191
Electronic ISSN 2326-5205
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 75
Issue 5
Pages 816-825
DOI https://doi.org/10.1002/art.42393
Public URL https://keele-repository.worktribe.com/output/424817
Publisher URL https://onlinelibrary.wiley.com/doi/10.1002/art.42393

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