Identification of low-frequency variants associated with gout and serum uric acid levels.

2.50
Hdl Handle:
http://hdl.handle.net/2336/226412
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; 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
Citation:
Nat. Genet. 2011, 43(11):1127-30
Issue Date:
Nov-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.
Description:
To access publisher full text version of this article. Please click on the hyperlink in Additional Links field.
Additional Links:
http://dx.doi.org/10.1038/ng.972
Rights:
Archived with thanks to Nature genetics

Full metadata record

DC FieldValue Language
dc.contributor.authorSulem, Patricken_GB
dc.contributor.authorGudbjartsson, Daniel Fen_GB
dc.contributor.authorWalters, G Bragien_GB
dc.contributor.authorHelgadottir, Hafdis Ten_GB
dc.contributor.authorHelgason, Agnaren_GB
dc.contributor.authorGudjonsson, Sigurjon Aen_GB
dc.contributor.authorZanon, Carloen_GB
dc.contributor.authorBesenbacher, Sorenen_GB
dc.contributor.authorBjornsdottir, Gydaen_GB
dc.contributor.authorMagnusson, Olafur Ten_GB
dc.contributor.authorMagnusson, Gislien_GB
dc.contributor.authorHjartarson, Eirikuren_GB
dc.contributor.authorSaemundsdottir, Jonaen_GB
dc.contributor.authorGylfason, Arnalduren_GB
dc.contributor.authorJonasdottir, Adalbjorgen_GB
dc.contributor.authorHolm, Hilmaen_GB
dc.contributor.authorKarason, Arien_GB
dc.contributor.authorRafnar, Thorunnen_GB
dc.contributor.authorStefansson, Hreinnen_GB
dc.contributor.authorAndreassen, Ole Aen_GB
dc.contributor.authorPedersen, Jesper Hen_GB
dc.contributor.authorPack, Allan Ien_GB
dc.contributor.authorde Visser, Marieke C Hen_GB
dc.contributor.authorKiemeney, Lambertus Aen_GB
dc.contributor.authorGeirsson, Arni Jen_GB
dc.contributor.authorEyjolfsson, Gudmundur Ien_GB
dc.contributor.authorOlafsson, Isleifuren_GB
dc.contributor.authorKong, Augustineen_GB
dc.contributor.authorMasson, Gislien_GB
dc.contributor.authorJonsson, Helgien_GB
dc.contributor.authorThorsteinsdottir, Unnuren_GB
dc.contributor.authorJonsdottir, Ingileifen_GB
dc.contributor.authorStefansson, Karien_GB
dc.date.accessioned2012-05-29T13:41:40Z-
dc.date.available2012-05-29T13:41:40Z-
dc.date.issued2011-11-
dc.date.submitted2012-05-29-
dc.identifier.citationNat. Genet. 2011, 43(11):1127-30en_GB
dc.identifier.issn1546-1718-
dc.identifier.pmid21983786-
dc.identifier.doi10.1038/ng.972-
dc.identifier.urihttp://hdl.handle.net/2336/226412-
dc.descriptionTo access publisher full text version of this article. Please click on the hyperlink in Additional Links field.en_GB
dc.description.abstractWe 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.en_GB
dc.description.sponsorshipEuropean Commission 200800en_GB
dc.language.isoenen
dc.publisherNature Publishing Groupen_GB
dc.relation.urlhttp://dx.doi.org/10.1038/ng.972en_GB
dc.rightsArchived with thanks to Nature geneticsen_GB
dc.subject.meshGouten_GB
dc.subject.meshHumansen_GB
dc.subject.meshIcelanden_GB
dc.subject.meshMutation, Missenseen_GB
dc.subject.meshPolymorphism, Single Nucleotideen_GB
dc.subject.meshUric Aciden_GB
dc.titleIdentification of low-frequency variants associated with gout and serum uric acid levels.en
dc.typeArticleen
dc.contributor.departmentdeCODE genetics, Reykjavik, Iceland. patrick.sulem@decode.isen_GB
dc.identifier.journalNature geneticsen_GB

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