Aotearoa New Zealand Māori and Pacific population-specific gout risk variants: CLNK is a separate risk gene at the SLC2A9 locus.

Abstract

OBJECTIVE\nThe Māori and Pacific (Polynesian) population of Aotearoa New Zealand (NZ) 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.\n\n\nMETHODS\nA 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 (AF > 0.05). Candidate functional variants were tested for association with gout by multivariable-adjusted regression analysis in 2,528 individuals of Polynesian ancestry.\n\n\nRESULTS\nWe identified 26 variants common in the Polynesian population and uncommon in the European and East Asian populations. Three of the 26 population-specific variants were nominally associated with the risk of gout (rs1635712, KIAA0319, ORmeta = 1.28, Pmeta = 0.028; rs16869924, CLNK, ORmeta = 1.37, P meta = 0.0017; rs2070025, FGA, ORmeta = 1.34, P meta = 0.017). The CLNK variant, within the established SLC2A9 gout locus, was genetically-independent of the association signal at SLC2A9.\n\n\nCONCLUSION\nWe 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 association of this gene with gout.