title: Refining the impact of TCF7L2 gene variants on type 2 diabetes and adaptive evolution.
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.
authors.affiliation: deCODE genetics, 101 Reykjavik, Iceland. agnar@decode.is
authors.forename: Agnar
authors.initials: A
authors.lastname: Helgason
authors.forename: Snaebjörn
authors.initials: S
authors.lastname: Pálsson
authors.forename: Gudmar
authors.initials: G
authors.lastname: Thorleifsson
authors.forename: Struan F A
authors.initials: SF
authors.lastname: Grant
authors.forename: Valur
authors.initials: V
authors.lastname: Emilsson
authors.forename: Steinunn
authors.initials: S
authors.lastname: Gunnarsdottir
authors.forename: Adebowale
authors.initials: A
authors.lastname: Adeyemo
authors.forename: Yuanxiu
authors.initials: Y
authors.lastname: Chen
authors.forename: Guanjie
authors.initials: G
authors.lastname: Chen
authors.forename: Inga
authors.initials: I
authors.lastname: Reynisdottir
authors.forename: Rafn
authors.initials: R
authors.lastname: Benediktsson
authors.forename: Anke
authors.initials: A
authors.lastname: Hinney
authors.forename: Torben
authors.initials: T
authors.lastname: Hansen
authors.forename: Gitte
authors.initials: G
authors.lastname: Andersen
authors.forename: Knut
authors.initials: K
authors.lastname: Borch-Johnsen
authors.forename: Torben
authors.initials: T
authors.lastname: Jorgensen
authors.forename: Helmut
authors.initials: H
authors.lastname: Schäfer
authors.forename: Mezbah
authors.initials: M
authors.lastname: Faruque
authors.forename: Ayo
authors.initials: A
authors.lastname: Doumatey
authors.forename: Jie
authors.initials: J
authors.lastname: Zhou
authors.forename: Robert L
authors.initials: RL
authors.lastname: Wilensky
authors.forename: Muredach P
authors.initials: MP
authors.lastname: Reilly
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Rader
authors.forename: Yu
authors.initials: Y
authors.lastname: Bagger
authors.forename: Claus
authors.initials: C
authors.lastname: Christiansen
authors.forename: Gunnar
authors.initials: G
authors.lastname: Sigurdsson
authors.forename: Johannes
authors.initials: J
authors.lastname: Hebebrand
authors.forename: Oluf
authors.initials: O
authors.lastname: Pedersen
authors.forename: Unnur
authors.initials: U
authors.lastname: Thorsteinsdottir
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Gulcher
authors.forename: Augustine
authors.initials: A
authors.lastname: Kong
authors.forename: Charles
authors.initials: C
authors.lastname: Rotimi
authors.forename: Kári
authors.initials: K
authors.lastname: Stefánsson
mesh_terms: D044466:Asian People; D005075:Biological Evolution; D044383:Black People; D015992:Body Mass Index; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D007055:Iceland; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D012641:Selection, Genetic; D051820:TCF Transcription Factors / Q000235:genetics*; D058118:Transcription Factor 7-Like 2 Protein; D044465:White People
chemical_list: D051820:TCF Transcription Factors; C544894:TCF7L2 protein, human; D058118:Transcription Factor 7-Like 2 Protein