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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
Pedersen, Jesper H
Pack, Allan I
de Visser, Marieke C H
Kiemeney, Lambertus A
Geirsson, Arni J
Eyjolfsson, Gudmundur I
Olafsson, Isleifur
Kong, Augustine
Masson, Gisli
Jonsson, Helgi
Thorsteinsdottir, Unnur
Jonsdottir, Ingileif
Stefansson, Kari
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
Pedersen, Jesper H
Pack, Allan I
de Visser, Marieke C H
Kiemeney, Lambertus A
Geirsson, Arni J
Eyjolfsson, Gudmundur I
Olafsson, Isleifur
Kong, Augustine
Masson, Gisli
Jonsson, Helgi
Thorsteinsdottir, Unnur
Jonsdottir, Ingileif
Stefansson, Kari
Source :
Sulem , P , Gudbjartsson , D F , Walters , G B , Helgadottir , H T , Helgason , A , Gudjonsson , S A , Zanon , C , Besenbacher , S , Bjornsdottir , G , Magnusson , O T , Magnusson , G , Hjartarson , E , Saemundsdottir , J , Gylfason , A , Jonasdottir , A , Holm , H , Karason , A , Rafnar , T , Stefansson , H , Andreassen , O A , Pedersen , J H , Pack , A I , de Visser , M C H , Kiemeney , L A , Geirsson , A J , Eyjolfsson , G I , Olafsson , I , Kong , A , Masson , G , Jonsson , H , Thorsteinsdottir , U , Jonsdottir , I & Stefansson , K 2011 , ' Identification of low-frequency variants associated with gout and serum uric acid levels ' , Nature Genetics , vol. 43 , no. 11 , pp. 1127-30 .
Publication Year :
2011

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.

Details

Database :
OAIster
Journal :
Sulem , P , Gudbjartsson , D F , Walters , G B , Helgadottir , H T , Helgason , A , Gudjonsson , S A , Zanon , C , Besenbacher , S , Bjornsdottir , G , Magnusson , O T , Magnusson , G , Hjartarson , E , Saemundsdottir , J , Gylfason , A , Jonasdottir , A , Holm , H , Karason , A , Rafnar , T , Stefansson , H , Andreassen , O A , Pedersen , J H , Pack , A I , de Visser , M C H , Kiemeney , L A , Geirsson , A J , Eyjolfsson , G I , Olafsson , I , Kong , A , Masson , G , Jonsson , H , Thorsteinsdottir , U , Jonsdottir , I & Stefansson , K 2011 , ' Identification of low-frequency variants associated with gout and serum uric acid levels ' , Nature Genetics , vol. 43 , no. 11 , pp. 1127-30 .
Notes :
English
Publication Type :
Electronic Resource
Accession number :
edsoai.ocn826493913
Document Type :
Electronic Resource