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Novel functional variants for serum uric acid and total serum bilirubin levels in an Irish population

Tuesday, October 25, 2011 — Poster Session II

Noon – 2:00 p.m.

Natcher Conference Center

NHGRI

GEN/GENOM-4

Authors

  • C Cropp
  • Y Kim
  • A Molloy
  • J Mills
  • P Kirke
  • J Scott
  • L Brody
  • A Wilson
  • J Bailey-Wilson

Abstract

The catabolic products of purine and hemoglobin metabolism can directly cause disease and serve as pathologic markers of several disease states. We present results from a GWAS of the purine breakdown product, serum uric acid (URIC, mmol/L) and the major hemoglobin breakdown product, total serum bilirubin (TBIL, umol/L). Genotyping was performed with the Illumina 1M HumanOmni1-Quad chip. After quality control 2232 unrelated, healthy individuals from Trinity College Dublin and 757,533 SNPs were retained for association testing that was performed with simple univariate linear regression, assuming an additive genetic model (PLINK v1.0.7). Locus-specific heritability (h2) was calculated with R. For URIC, we replicated previously reported SNPs in SLC2A9 (rs6449213, h2=10%), WDR1 (rs717615, h2=3%), and ABCG2 (rs2199936, h2=2%) at genome-wide significance levels (p-value‚ȧ5e-08). The most significant results found were novel variants in SLC2A9: rs13111638 (p-value=4e-24, h2=9.5%) in an intronic region, and two coding SNPs, rs10939650 and rs13113918 (p-value=2e-22, 1e-21; h2=4.4%, 5.6% respectively). For TBIL, strong UGT1A signals were found including rs887829 (p-value=4e-156, h2=28%). Two non-synonymous SNPs in LOC339766 (rs6431631 & rs1500480, p-value=3e-09, 2e-08 respectively) were significantly associated with TBIL. In conclusion, common variants associated with URIC and TBIL were replicated and novel coding genetic variants were found in SLC2A9 and LOC339766, respectively.

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