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- Title
Identification of low-frequency variants associated with gout and serum uric acid levels.
- Authors
Sulem, Patrick; Gudbjartsson, Daniel F; Walters, G Bragi; Helgadottir, Hafdis T; Helgason, Agnar; Gudjonsson, Sigurjon A; Zanon, Carlo; Besenbacher, Soren; Bjornsdottir, Gyda; Magnusson, Olafur T; Magnusson, Gisli; Hjartarson, Eirikur; Saemundsdottir, Jona; Gylfason, Arnaldur; Jonasdottir, Adalbjorg; Holm, Hilma; Karason, Ari; Rafnar, Thorunn; Stefansson, Hreinn; Andreassen, Ole A
- Abstract
We tested 16 million SNPs, identified through whole-genome sequencing of 457 Icelanders, for association with gout and serum uric acid levels. Genotypes were imputed into 41,675 chip-genotyped Icelanders and their relatives, for effective sample sizes of 968 individuals with gout and 15,506 individuals for whom serum uric acid measurements were available. We identified a low-frequency missense variant (c.1580C>G) in ALDH16A1 associated with gout (OR = 3.12, P = 1.5 × 10?16, at-risk allele frequency = 0.019) and serum uric acid levels (effect = 0.36 s.d., P = 4.5 × 10?21). We confirmed the association with gout by performing Sanger sequencing on 6,017 Icelanders. The association with gout was stronger in males relative to females. We also found a second variant on chromosome 1 associated with gout (OR = 1.92, P = 0.046, at-risk allele frequency = 0.986) and serum uric acid levels (effect = 0.48 s.d., P = 4.5 × 10?16). This variant is close to a common variant previously associated with serum uric acid levels. This work illustrates how whole-genome sequencing data allow the detection of associations between low-frequency variants and complex traits.
- Subjects
GOUT; SERUM; URIC acid; HUMAN genome; GENE frequency; GENOTYPE-environment interaction
- Publication
Nature Genetics, 2011, Vol 43, Issue 11, p1127
- ISSN
1061-4036
- Publication type
Article
- DOI
10.1038/ng.972