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

Agnar Helgason; Snaebjörn Pálsson; Gudmar Thorleifsson; Struan F A Grant; Valur Emilsson; Steinunn Gunnarsdottir; Adebowale Adeyemo; Yuanxiu Chen; Guanjie Chen; Inga Reynisdottir; Rafn Benediktsson; Anke Hinney; Torben Hansen; Gitte Andersen; Knut Borch-Johnsen; Torben Jorgensen; Helmut Schäfer; Mezbah Faruque; Ayo Doumatey; Jie Zhou; Robert L Wilensky; Muredach P Reilly; Daniel J Rader; Yu Bagger; Claus Christiansen; Gunnar Sigurdsson; Johannes Hebebrand; Oluf Pedersen; Unnur Thorsteinsdottir; Jeffrey R Gulcher; Augustine Kong; Charles Rotimi; Kári Stefánsson

doi:10.1038/ng1960

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

Agnar Helgason, Snaebjörn Pálsson, Gudmar Thorleifsson, Struan F A Grant, Valur Emilsson, Steinunn Gunnarsdottir, Adebowale Adeyemo, Yuanxiu Chen, Guanjie Chen, Inga Reynisdottir, Rafn Benediktsson, Anke Hinney, Torben Hansen, Gitte Andersen, Knut Borch-Johnsen, Torben Jorgensen, Helmut Schäfer, Mezbah Faruque, Ayo Doumatey, Jie ZhouRobert L Wilensky, Muredach P Reilly, Daniel J Rader, Yu Bagger, Claus Christiansen, Gunnar Sigurdsson, Johannes Hebebrand, Oluf Pedersen, Unnur Thorsteinsdottir, Jeffrey R Gulcher, Augustine Kong, Charles Rotimi, Kári Stefánsson

352 Citations (Scopus)

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.

Original language	English
Journal	Nature Genetics
Volume	39
Issue number	2
Pages (from-to)	218-25
Number of pages	8
ISSN	1061-4036
DOIs	https://doi.org/10.1038/ng1960
Publication status	Published - 2007

Keywords

African Continental Ancestry Group
Asian Continental Ancestry Group
Biological Evolution
Body Mass Index
Case-Control Studies
Diabetes Mellitus, Type 2
European Continental Ancestry Group
Female
Genetic Predisposition to Disease
Genetic Variation
Haplotypes
Humans
Iceland
Male
Polymorphism, Single Nucleotide
Risk
Selection, Genetic
TCF Transcription Factors
Transcription Factor 7-Like 2 Protein

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/ng1960

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Helgason, A., Pálsson, S., Thorleifsson, G., Grant, S. F. A., Emilsson, V., Gunnarsdottir, S., Adeyemo, A., Chen, Y., Chen, G., Reynisdottir, I., Benediktsson, R., Hinney, A., Hansen, T., Andersen, G., Borch-Johnsen, K., Jorgensen, T., Schäfer, H., Faruque, M., Doumatey, A., ... Stefánsson, K. (2007). Refining the impact of TCF7L2 gene variants on type 2 diabetes and adaptive evolution. Nature Genetics, 39(2), 218-25. https://doi.org/10.1038/ng1960

Helgason, A, Pálsson, S, Thorleifsson, G, Grant, SFA, Emilsson, V, Gunnarsdottir, S, Adeyemo, A, Chen, Y, Chen, G, Reynisdottir, I, Benediktsson, R, Hinney, A, Hansen, T, Andersen, G, Borch-Johnsen, K, Jorgensen, T, Schäfer, H, Faruque, M, Doumatey, A, Zhou, J, Wilensky, RL, Reilly, MP, Rader, DJ, Bagger, Y, Christiansen, C, Sigurdsson, G, Hebebrand, J, Pedersen, O, Thorsteinsdottir, U, Gulcher, JR, Kong, A, Rotimi, C & Stefánsson, K 2007, 'Refining the impact of TCF7L2 gene variants on type 2 diabetes and adaptive evolution', Nature Genetics, vol. 39, no. 2, pp. 218-25. https://doi.org/10.1038/ng1960

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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.",

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doi = "10.1038/ng1960",

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T1 - Refining the impact of TCF7L2 gene variants on type 2 diabetes and adaptive evolution

AU - Helgason, Agnar

AU - Pálsson, Snaebjörn

AU - Thorleifsson, Gudmar

AU - Grant, Struan F A

AU - Emilsson, Valur

AU - Gunnarsdottir, Steinunn

AU - Adeyemo, Adebowale

AU - Chen, Yuanxiu

AU - Chen, Guanjie

AU - Reynisdottir, Inga

AU - Benediktsson, Rafn

AU - Hinney, Anke

AU - Hansen, Torben

AU - Andersen, Gitte

AU - Borch-Johnsen, Knut

AU - Jorgensen, Torben

AU - Schäfer, Helmut

AU - Faruque, Mezbah

AU - Doumatey, Ayo

AU - Zhou, Jie

AU - Wilensky, Robert L

AU - Reilly, Muredach P

AU - Rader, Daniel J

AU - Bagger, Yu

AU - Christiansen, Claus

AU - Sigurdsson, Gunnar

AU - Hebebrand, Johannes

AU - Pedersen, Oluf

AU - Thorsteinsdottir, Unnur

AU - Gulcher, Jeffrey R

AU - Kong, Augustine

AU - Rotimi, Charles

AU - Stefánsson, Kári

PY - 2007

Y1 - 2007

N2 - 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.

AB - 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.

KW - African Continental Ancestry Group

KW - Asian Continental Ancestry Group

KW - Biological Evolution

KW - Body Mass Index

KW - Case-Control Studies

KW - Diabetes Mellitus, Type 2

KW - European Continental Ancestry Group

KW - Female

KW - Genetic Predisposition to Disease

KW - Genetic Variation

KW - Haplotypes

KW - Humans

KW - Iceland

KW - Male

KW - Polymorphism, Single Nucleotide

KW - Risk

KW - Selection, Genetic

KW - TCF Transcription Factors

KW - Transcription Factor 7-Like 2 Protein

U2 - 10.1038/ng1960

DO - 10.1038/ng1960

M3 - Journal article

C2 - 17206141

SN - 1061-4036

VL - 39

SP - 218

EP - 225

JO - Nature: New biology

JF - Nature: New biology

IS - 2

ER -

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

Abstract

Keywords

UN SDGs

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