Refining the impact of TCF7L2 gene variants on type 2 diabetes and adaptive evolution

2.50
Hdl Handle:
http://hdl.handle.net/2336/13070
Title:
Refining the impact of TCF7L2 gene variants on type 2 diabetes and adaptive evolution
Authors:
Helgason, Agnar; Palsson, Snaebjorn; Thorleifsson, Gudmar; Grant, Struan F A; Emilsson, Valur; Gunnarsdottir, Steinunn; Adeyemo, Adebowale; Chen, Yuanxiu; Chen, Guanjie; Reynisdottir, Inga; Benediktsson, Rafn; Hinney, Anke; Hansen, Torben; Andersen, Gitte; Borch-Johnsen, Knut; Jorgensen, Torben; Schäfer, Helmut; Faruque, Mezbah; Doumatey, Ayo; Zhou, Jie; Wilensky, Robert L; Reilly, Muredach P; Rader, Daniel J; Bagger, Yu; Christiansen, Claus; Sigurdsson, Gunnar; Hebebrand, Johannes; Pedersen, Oluf; Thorsteinsdottir, Unnur; Gulcher, Jeffrey R; Kong, Augustine; Rotimi, Charles; Stefansson, Kari
Citation:
Nat. Genet. 2007, 39(2):218-25
Issue Date:
1-Feb-2007
Abstract:
We recently described an association between risk of type 2diabetes and variants in the transcription factor 7-like 2 gene (TCF7L2; formerly TCF4), with a population attributable risk (PAR) of 17%-28% in three populations of European ancestry. Here, we refine the definition of the TCF7L2 type 2diabetes risk variant, HapB(T2D), to the ancestral T allele of a SNP, rs7903146, through replication in West African and Danish type 2 diabetes case-control studies and an expanded Icelandic study. We also identify another variant of the same gene, HapA, that shows evidence of positive selection in East Asian, European and West African populations. Notably, HapA shows a suggestive association with body mass index and altered concentrations of the hunger-satiety hormones ghrelin and leptin in males, indicating that the selective advantage of HapA may have been mediated through effects on energy metabolism.
Description:
To access publisher full text version of this article. Please click on the hyperlink in Additional Links field
Additional Links:
http://www.nature.com/ng/journal/v39/n2/abs/ng1960.html

Full metadata record

DC FieldValue Language
dc.contributor.authorHelgason, Agnar-
dc.contributor.authorPalsson, Snaebjorn-
dc.contributor.authorThorleifsson, Gudmar-
dc.contributor.authorGrant, Struan F A-
dc.contributor.authorEmilsson, Valur-
dc.contributor.authorGunnarsdottir, Steinunn-
dc.contributor.authorAdeyemo, Adebowale-
dc.contributor.authorChen, Yuanxiu-
dc.contributor.authorChen, Guanjie-
dc.contributor.authorReynisdottir, Inga-
dc.contributor.authorBenediktsson, Rafn-
dc.contributor.authorHinney, Anke-
dc.contributor.authorHansen, Torben-
dc.contributor.authorAndersen, Gitte-
dc.contributor.authorBorch-Johnsen, Knut-
dc.contributor.authorJorgensen, Torben-
dc.contributor.authorSchäfer, Helmut-
dc.contributor.authorFaruque, Mezbah-
dc.contributor.authorDoumatey, Ayo-
dc.contributor.authorZhou, Jie-
dc.contributor.authorWilensky, Robert L-
dc.contributor.authorReilly, Muredach P-
dc.contributor.authorRader, Daniel J-
dc.contributor.authorBagger, Yu-
dc.contributor.authorChristiansen, Claus-
dc.contributor.authorSigurdsson, Gunnar-
dc.contributor.authorHebebrand, Johannes-
dc.contributor.authorPedersen, Oluf-
dc.contributor.authorThorsteinsdottir, Unnur-
dc.contributor.authorGulcher, Jeffrey R-
dc.contributor.authorKong, Augustine-
dc.contributor.authorRotimi, Charles-
dc.contributor.authorStefansson, Kari-
dc.date.accessioned2007-08-02T11:01:08Z-
dc.date.available2007-08-02T11:01:08Z-
dc.date.issued2007-02-01-
dc.date.submitted2007-08-02-
dc.identifier.citationNat. Genet. 2007, 39(2):218-25en
dc.identifier.issn1061-4036-
dc.identifier.pmid17206141-
dc.identifier.doi10.1038/ng1960-
dc.identifier.urihttp://hdl.handle.net/2336/13070-
dc.descriptionTo access publisher full text version of this article. Please click on the hyperlink in Additional Links fielden
dc.description.abstractWe recently described an association between risk of type 2diabetes and variants in the transcription factor 7-like 2 gene (TCF7L2; formerly TCF4), with a population attributable risk (PAR) of 17%-28% in three populations of European ancestry. Here, we refine the definition of the TCF7L2 type 2diabetes risk variant, HapB(T2D), to the ancestral T allele of a SNP, rs7903146, through replication in West African and Danish type 2 diabetes case-control studies and an expanded Icelandic study. We also identify another variant of the same gene, HapA, that shows evidence of positive selection in East Asian, European and West African populations. Notably, HapA shows a suggestive association with body mass index and altered concentrations of the hunger-satiety hormones ghrelin and leptin in males, indicating that the selective advantage of HapA may have been mediated through effects on energy metabolism.en
dc.language.isoenen
dc.publisherNature Pub. Co.en
dc.relation.urlhttp://www.nature.com/ng/journal/v39/n2/abs/ng1960.htmlen
dc.subject.meshAfrican Continental Ancestry Groupen
dc.subject.meshIcelanden
dc.subject.meshBody Mass Indexen
dc.subject.meshCase-Control Studiesen
dc.subject.meshDiabetes Mellitus, Type 2en
dc.subject.meshGenetic Predisposition to Diseaseen
dc.subject.meshPolymorphism, Single Nucleotideen
dc.subject.meshTCF Transcription Factorsen
dc.titleRefining the impact of TCF7L2 gene variants on type 2 diabetes and adaptive evolutionen
dc.typeArticleen
dc.format.digYES-

Related articles on PubMed

All Items in Hirsla are protected by copyright, with all rights reserved, unless otherwise indicated.