Genome-wide association of serum uric acid concentration: replication of sequence variants in an island population of the Adriatic coast of Croatia.
A genome-wide association study of serum uric acid (SUA) laevels was performed in a relatively isolated population of European descent from an island of the Adriatic coast of Croatia. The study sample included 532 unrelated and 768 related individuals from 235 pedigrees. Inflation due to relatedness was controlled by using genomic control. Genetic association was assessed with 2,241,249 single nucleotide polymorphisms (SNPs) in 1300 samples after adjusting for age and gender. Our study replicated four previously reported SUA loci (SLC2A9, ABCG2, RREB1, and SLC22A12). The strongest association was found with a SNP in SLC2A9 (rs13129697, P=2.33×10(-19)), which exhibited significant gender-specific effects, 35.76 μmol/L (P=2.11×10(-19)) in females and 19.58 μmol/L (P=5.40×10(-5)) in males. Within this region of high linkage disequilibrium, we also detected a strong association with a nonsynonymous SNP, rs16890979 (P=2.24×10(-17)), a putative causal variant for SUA variation. In addition, we identified several novel loci suggestive of association with uric acid levels (SEMA5A, TMEM18, SLC28A2, and ODZ2), although the P-values (P<5×10(-6)) did not reach the threshold of genome-wide significance. Together, these findings provide further confirmation of previously reported uric-acid-related genetic variants and highlight suggestive new loci for additional investigation.
Center for Genome Information, Department of Environmental Health, University of Cincinnati, and Cincinnati Children's Hospital, Cincinnati, OH 45267, USA.
Rebekah
R
Karns
Ge
G
Zhang
Guangyun
G
Sun
Subba
S
Rao Indugula
Hong
H
Cheng
Dubravka
D
Havas-Augustin
Natalija
N
Novokmet
Dusko
D
Rudan
Zijad
Z
Durakovic
Sasa
S
Missoni
Ranajit
R
Chakraborty
Pavao
P
Rudan
Ranjan
R
Deka
D017523:Croatia; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D014527:Uric Acid / Q000097:blood*
D014527:Uric Acid