RT Journal Article
SR Electronic
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
FD The Journal of Rheumatology
SP jrheum.201684
DO 10.3899/jrheum.201684
A1 Aichang Ji
A1 Amara Shaukat
A1 Riku Takei
A1 Matthew Bixley
A1 Murray Cadzow
A1 Ruth K.  Topless
A1 Tanya J.  Major
A1 Amanda Phipps-Green
A1 Marilyn E.  Merriman
A1 Jennie  Harré Hindmarsh
A1 Lisa K.  Stamp
A1 Nicola Dalbeth
A1 Changgui Li
A1 Tony R.  Merriman
YR 2021
UL http://www.jrheum.org/content/early/2021/08/26/jrheum.201684.abstract
AB 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.