Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose: The prevalence of gout in New Zealand Polynesian (Māori and Pacific) populations is approximately twice that of the New Zealand European population, with a younger average age of onset and more severe symptoms. We aimed to undertake a genome-wide association study of gout in Polynesian people. Additionally, we assessed the differences in genetic susceptibility to gout between Eastern and Western Polynesian individuals to further identify regions involved in gout risk.
Methods: Polynesian individuals with clinically-ascertained gout (ngout = 929) or with no history of gout (ncontrol = 861) were recruited. This cohort was divided into Eastern (New Zealand and Cook Island Māori; ngout = 566, ncontrol = 605) and Western Polynesian (Samoan, Tongan, Tokelauan and Niuean; ngout = 363, ncontrol = 256) based on self-reported ancestry and principal component clusters. Genotyping across the Infinium CoreExome chip and logistic regression analyses adjusted for sex and age were conducted. Differential effect of each variant in the two cohorts was compared using Cochran’s Q-test during meta-analysis, in order to identify heterogeneous effects. Genome-wide significant association was set at P < 5.0×10-8 and suggestive association at P < 1.0×10-5.
Results: The only genome-wide significant result in the combined Polynesian cohort was at ABCG2 (rs2231142: OR = 2.31, P = 9.7×10-14). The Western Polynesian cohort showed a genome-wide significant effect for rs2231142 (OR = 2.65, P = 1.4×10-11), but the Eastern Polynesian cohort did not (OR = 1.87, P = 5.2×10-4). These results were not significantly different (PQ = 0.13). Two other variants in the ABCG2 locus (rs6857847 and rs3737488) had significant Q-test p-values (PQ = 5.1×10-8 and 2.8×10-8), with strong protective effects in Western Polynesian (OR = 0.47, P = 2.0×10-7; and OR = 0.47, P = 1.36×10-7), but weak susceptibility effects in Eastern Polynesian people (OR = 1.22, P = 4.3×10-2; and OR = 1.23, P = 3.5×10-2). A variant on Chromosome 18 (rs4939827) also produced a genome-wide significant Q-test p-value (PQ = 1.5×10-8). This variant had a suggestively significant protective effect in Western Polynesian (OR = 0.53, P = 7.4×10-6) and a non-significant susceptibility effect in Eastern Polynesian individuals (OR = 1.38, P = 5.0×10-4).
Conclusion: Genome-wide association analysis of Polynesian cohorts revealed a significant effect at ABCG2 in the Western Polynesian, but not Eastern Polynesian, cohort. There was a genome-wide significant difference in effect at rs4939827, within an intron of SMAD7, a gene that has been associated with inflammatory bowel disease, colorectal cancer, and chronic kidney disease and that is involved in the regulation of TGF-beta signalling.
To cite this abstract in AMA style:Flynn T, Topless R, Cadzow M, Phipps-Green A, Burns N, Dalbeth N, Stamp LK, Harre Hindmarsh J, Merriman TR. Genome-Wide Association Study of Gout in New Zealand Polynesian People [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/genome-wide-association-study-of-gout-in-new-zealand-polynesian-people/. Accessed July 13, 2020.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/genome-wide-association-study-of-gout-in-new-zealand-polynesian-people/