TY - JOUR T1 - Aotearoa New Zealand Māori and Pacific Population-amplified Gout Risk Variants: <em>CLNK</em> Is a Separate Risk Gene at the <em>SLC2A9</em> Locus JF - The Journal of Rheumatology JO - J Rheumatol DO - 10.3899/jrheum.201684 SP - jrheum.201684 AU - Aichang Ji AU - Amara Shaukat AU - Riku Takei AU - Matthew Bixley AU - Murray Cadzow AU - Ruth K. Topless AU - Tanya J. Major AU - Amanda Phipps-Green AU - Marilyn E. Merriman AU - Jennie Harré Hindmarsh AU - Lisa K. Stamp AU - Nicola Dalbeth AU - Changgui Li AU - Tony R. Merriman Y1 - 2021/07/01 UR - http://www.jrheum.org/content/early/2021/08/26/jrheum.201684.abstract N2 - Objective The Māori and Pacific (Polynesian) population of Aotearoa New Zealand has a high prevalence of gout. Our aim was to identify potentially functional missense genetic variants in candidate inflammatory genes amplified in frequency that may underlie the increased prevalence of gout in Polynesian populations. Methods A list of 712 inflammatory disease-related genes was generated. An in silico targeted exome set was extracted from whole genome sequencing data in people with gout of various ancestral groups (Polynesian, European, East Asian; n = 55, 780, 135, respectively) to identify Polynesian-amplified common missense variants (minor allele frequency &gt; 0.05). Candidate functional variants were tested for association with gout by multivariable-adjusted regression analysis in 2528 individuals of Polynesian ancestry. Results We identified 26 variants common in the Polynesian population and uncommon in the European and East Asian populations. Three of the 26 population-amplified variants were nominally associated with the risk of gout (rs1635712 [KIAA0319], ORmeta = 1.28, Pmeta = 0.03; rs16869924 [CLNK], ORmeta = 1.37, Pmeta = 0.002; rs2070025 [fibrinogen A alpha chain (FGA)], ORmeta = 1.34, Pmeta = 0.02). The CLNK variant, within the established SLC2A9 gout locus, was genetically independent of the association signal at SLC2A9. Conclusion We provide nominal evidence for the existence of population-amplified genetic variants conferring risk of gout in Polynesian populations. Polymorphisms in CLNK have previously been associated with gout in other populations, supporting our evidence for the association of this gene with gout. ER -