Genome-Wide Association of Serum Uric Acid Concentration: Replication of Sequence Variants in an Island Population of the Adriatic Coast of Croatia

Rebekah Karns, Ge Zhang, Guangyun Sun, Subba Rao Indugula, Hong Cheng, Dubravka Havas-Augustin, Natalija Novokmet, Dusko Rudan, Zijad Durakovic, Sasa Missoni, Ranajit Chakraborty, Pavao Rudan, Ranjan Deka

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)121-127
Number of pages7
JournalAnnals of Human Genetics
Volume76
Issue number2
DOIs
StatePublished - 1 Mar 2012

Fingerprint

Croatia
Uric Acid
Islands
Genome
Single Nucleotide Polymorphism
Serum
Population
Genome-Wide Association Study
Linkage Disequilibrium
Economic Inflation
Pedigree

Keywords

  • Adriatic island population
  • Genome-wide association
  • Serum uric acid

Cite this

Karns, Rebekah ; Zhang, Ge ; Sun, Guangyun ; Rao Indugula, Subba ; Cheng, Hong ; Havas-Augustin, Dubravka ; Novokmet, Natalija ; Rudan, Dusko ; Durakovic, Zijad ; Missoni, Sasa ; Chakraborty, Ranajit ; Rudan, Pavao ; Deka, Ranjan. / Genome-Wide Association of Serum Uric Acid Concentration : Replication of Sequence Variants in an Island Population of the Adriatic Coast of Croatia. In: Annals of Human Genetics. 2012 ; Vol. 76, No. 2. pp. 121-127.
@article{223b94e452244eaab5c017d989f9da27,
title = "Genome-Wide Association of Serum Uric Acid Concentration: Replication of Sequence Variants in an Island Population of the Adriatic Coast of Croatia",
abstract = "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.",
keywords = "Adriatic island population, Genome-wide association, Serum uric acid",
author = "Rebekah Karns and Ge Zhang and Guangyun Sun and {Rao Indugula}, Subba and Hong Cheng and Dubravka Havas-Augustin and Natalija Novokmet and Dusko Rudan and Zijad Durakovic and Sasa Missoni and Ranajit Chakraborty and Pavao Rudan and Ranjan Deka",
year = "2012",
month = "3",
day = "1",
doi = "10.1111/j.1469-1809.2011.00698.x",
language = "English",
volume = "76",
pages = "121--127",
journal = "Annals of Human Genetics",
issn = "0003-4800",
publisher = "Wiley-Blackwell Publishing Ltd",
number = "2",

}

Karns, R, Zhang, G, Sun, G, Rao Indugula, S, Cheng, H, Havas-Augustin, D, Novokmet, N, Rudan, D, Durakovic, Z, Missoni, S, Chakraborty, R, Rudan, P & Deka, R 2012, 'Genome-Wide Association of Serum Uric Acid Concentration: Replication of Sequence Variants in an Island Population of the Adriatic Coast of Croatia', Annals of Human Genetics, vol. 76, no. 2, pp. 121-127. https://doi.org/10.1111/j.1469-1809.2011.00698.x

Genome-Wide Association of Serum Uric Acid Concentration : Replication of Sequence Variants in an Island Population of the Adriatic Coast of Croatia. / Karns, Rebekah; Zhang, Ge; Sun, Guangyun; Rao Indugula, Subba; Cheng, Hong; Havas-Augustin, Dubravka; Novokmet, Natalija; Rudan, Dusko; Durakovic, Zijad; Missoni, Sasa; Chakraborty, Ranajit; Rudan, Pavao; Deka, Ranjan.

In: Annals of Human Genetics, Vol. 76, No. 2, 01.03.2012, p. 121-127.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Genome-Wide Association of Serum Uric Acid Concentration

T2 - Replication of Sequence Variants in an Island Population of the Adriatic Coast of Croatia

AU - Karns, Rebekah

AU - Zhang, Ge

AU - Sun, Guangyun

AU - Rao Indugula, Subba

AU - Cheng, Hong

AU - Havas-Augustin, Dubravka

AU - Novokmet, Natalija

AU - Rudan, Dusko

AU - Durakovic, Zijad

AU - Missoni, Sasa

AU - Chakraborty, Ranajit

AU - Rudan, Pavao

AU - Deka, Ranjan

PY - 2012/3/1

Y1 - 2012/3/1

N2 - 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.

AB - 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.

KW - Adriatic island population

KW - Genome-wide association

KW - Serum uric acid

UR - http://www.scopus.com/inward/record.url?scp=84862828563&partnerID=8YFLogxK

U2 - 10.1111/j.1469-1809.2011.00698.x

DO - 10.1111/j.1469-1809.2011.00698.x

M3 - Article

C2 - 22229870

AN - SCOPUS:84862828563

VL - 76

SP - 121

EP - 127

JO - Annals of Human Genetics

JF - Annals of Human Genetics

SN - 0003-4800

IS - 2

ER -