A variant in CDKAL1 influences insulin response and risk of type 2 diabetes

V. Steinthorsdottir; G. Thorleifsson; I. Reynisdottir; R. Benediktsson; T. Jonsdottir; G.B. Walters; U. Styrkarsdottir; S. Gretarsdottir; V. Emilsson; S. Ghosh; A. Baker; S. Snorradottir; H. Bjarnason; M.C. Ng; T. Hansen; Y. Bagger; R.L. Wilensky; M.P. Reilly; A. Adeyemo; Y. Chen; J. Zhou; V. Gudnason; G. Chen; H. Huang; K. Lashley; A. Doumatey; W.Y. So; R.C. Ma; G. Andersen; K. Borch Johnsen; T. Jorgensen; J.V. van Vliet-Ostaptchouk; M.H. Hofker; C. Wijmenga; C. Christiansen; D.J. Rader; C. Rotimi; M. Gurney; J.C. Chan; O. Pedersen; G. Sigurdsson; J.R. Gulcher; U. Thorsteinsdottir; A. Kong; K. Stefansson

doi:10.1038/ng2043

A variant in CDKAL1 influences insulin response and risk of type 2 diabetes

V. Steinthorsdottir
, G. Thorleifsson
, I. Reynisdottir
, R. Benediktsson
, T. Jonsdottir
, G.B. Walters
, U. Styrkarsdottir
, S. Gretarsdottir
, V. Emilsson
, S. Ghosh
, A. Baker
, S. Snorradottir
, H. Bjarnason
, M.C. Ng
, T. Hansen
, Y. Bagger
, R.L. Wilensky
, M.P. Reilly
, A. Adeyemo
, Y. Chen

J. Zhou, V. Gudnason, G. Chen, H. Huang, K. Lashley, A. Doumatey, W.Y. So, R.C. Ma, G. Andersen, K. Borch Johnsen, T. Jorgensen, J.V. van Vliet-Ostaptchouk, M.H. Hofker, C. Wijmenga, C. Christiansen, D.J. Rader, C. Rotimi, M. Gurney, J.C. Chan, O. Pedersen, G. Sigurdsson, J.R. Gulcher, U. Thorsteinsdottir, A. Kong, K. Stefansson^*

^*Corresponding author for this work

NUTRIM - Institute of Nutrition and Translational Research in Metabolism

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

We conducted a genome-wide association study for type 2 diabetes (T2D) in Icelandic cases and controls, and we found that a previously described variant in the transcription factor 7-like 2 gene (TCF7L2) gene conferred the most significant risk. In addition to confirming two recently identified risk variants, we identified a variant in the CDKAL1 gene that was associated with T2D in individuals of European ancestry (allele-specific odds ratio (OR) = 1.20 (95% confidence interval, 1.13-1.27), P = 7.7 x 10(-9)) and individuals from Hong Kong of Han Chinese ancestry (OR = 1.25 (1.11-1.40), P = 0.00018). The genotype OR of this variant suggested that the effect was substantially stronger in homozygous carriers than in heterozygous carriers. The ORs for homozygotes were 1.50 (1.31-1.72) and 1.55 (1.23-1.95) in the European and Hong Kong groups, respectively. The insulin response for homozygotes was approximately 20% lower than for heterozygotes or noncarriers, suggesting that this variant confers risk of T2D through reduced insulin secretion.

Original language	English
Pages (from-to)	770-775
Journal	Nature Genetics
Volume	39
Issue number	6
DOIs	https://doi.org/10.1038/ng2043
Publication status	Published - 1 Jan 2007

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Steinthorsdottir, V., Thorleifsson, G., Reynisdottir, I., Benediktsson, R., Jonsdottir, T., Walters, G. B., Styrkarsdottir, U., Gretarsdottir, S., Emilsson, V., Ghosh, S., Baker, A., Snorradottir, S., Bjarnason, H., Ng, M. C., Hansen, T., Bagger, Y., Wilensky, R. L., Reilly, M. P., Adeyemo, A., ... Stefansson, K. (2007). A variant in CDKAL1 influences insulin response and risk of type 2 diabetes. Nature Genetics, 39(6), 770-775. https://doi.org/10.1038/ng2043

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title = "A variant in CDKAL1 influences insulin response and risk of type 2 diabetes",

abstract = "We conducted a genome-wide association study for type 2 diabetes (T2D) in Icelandic cases and controls, and we found that a previously described variant in the transcription factor 7-like 2 gene (TCF7L2) gene conferred the most significant risk. In addition to confirming two recently identified risk variants, we identified a variant in the CDKAL1 gene that was associated with T2D in individuals of European ancestry (allele-specific odds ratio (OR) = 1.20 (95\% confidence interval, 1.13-1.27), P = 7.7 x 10(-9)) and individuals from Hong Kong of Han Chinese ancestry (OR = 1.25 (1.11-1.40), P = 0.00018). The genotype OR of this variant suggested that the effect was substantially stronger in homozygous carriers than in heterozygous carriers. The ORs for homozygotes were 1.50 (1.31-1.72) and 1.55 (1.23-1.95) in the European and Hong Kong groups, respectively. The insulin response for homozygotes was approximately 20\% lower than for heterozygotes or noncarriers, suggesting that this variant confers risk of T2D through reduced insulin secretion.",

author = "V. Steinthorsdottir and G. Thorleifsson and I. Reynisdottir and R. Benediktsson and T. Jonsdottir and G.B. Walters and U. Styrkarsdottir and S. Gretarsdottir and V. Emilsson and S. Ghosh and A. Baker and S. Snorradottir and H. Bjarnason and M.C. Ng and T. Hansen and Y. Bagger and R.L. Wilensky and M.P. Reilly and A. Adeyemo and Y. Chen and J. Zhou and V. Gudnason and G. Chen and H. Huang and K. Lashley and A. Doumatey and W.Y. So and R.C. Ma and G. Andersen and \{Borch Johnsen\}, K. and T. Jorgensen and \{van Vliet-Ostaptchouk\}, J.V. and M.H. Hofker and C. Wijmenga and C. Christiansen and D.J. Rader and C. Rotimi and M. Gurney and J.C. Chan and O. Pedersen and G. Sigurdsson and J.R. Gulcher and U. Thorsteinsdottir and A. Kong and K. Stefansson",

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Steinthorsdottir, V, Thorleifsson, G, Reynisdottir, I, Benediktsson, R, Jonsdottir, T, Walters, GB, Styrkarsdottir, U, Gretarsdottir, S, Emilsson, V, Ghosh, S, Baker, A, Snorradottir, S, Bjarnason, H, Ng, MC, Hansen, T, Bagger, Y, Wilensky, RL, Reilly, MP, Adeyemo, A, Chen, Y, Zhou, J, Gudnason, V, Chen, G, Huang, H, Lashley, K, Doumatey, A, So, WY, Ma, RC, Andersen, G, Borch Johnsen, K, Jorgensen, T, van Vliet-Ostaptchouk, JV, Hofker, MH, Wijmenga, C, Christiansen, C, Rader, DJ, Rotimi, C, Gurney, M, Chan, JC, Pedersen, O, Sigurdsson, G, Gulcher, JR, Thorsteinsdottir, U, Kong, A & Stefansson, K 2007, 'A variant in CDKAL1 influences insulin response and risk of type 2 diabetes', Nature Genetics, vol. 39, no. 6, pp. 770-775. https://doi.org/10.1038/ng2043

TY - JOUR

T1 - A variant in CDKAL1 influences insulin response and risk of type 2 diabetes

AU - Steinthorsdottir, V.

AU - Thorleifsson, G.

AU - Reynisdottir, I.

AU - Benediktsson, R.

AU - Jonsdottir, T.

AU - Walters, G.B.

AU - Styrkarsdottir, U.

AU - Gretarsdottir, S.

AU - Emilsson, V.

AU - Ghosh, S.

AU - Baker, A.

AU - Snorradottir, S.

AU - Bjarnason, H.

AU - Ng, M.C.

AU - Hansen, T.

AU - Bagger, Y.

AU - Wilensky, R.L.

AU - Reilly, M.P.

AU - Adeyemo, A.

AU - Chen, Y.

AU - Zhou, J.

AU - Gudnason, V.

AU - Chen, G.

AU - Huang, H.

AU - Lashley, K.

AU - Doumatey, A.

AU - So, W.Y.

AU - Ma, R.C.

AU - Andersen, G.

AU - Borch Johnsen, K.

AU - Jorgensen, T.

AU - van Vliet-Ostaptchouk, J.V.

AU - Hofker, M.H.

AU - Wijmenga, C.

AU - Christiansen, C.

AU - Rader, D.J.

AU - Rotimi, C.

AU - Gurney, M.

AU - Chan, J.C.

AU - Pedersen, O.

AU - Sigurdsson, G.

AU - Gulcher, J.R.

AU - Thorsteinsdottir, U.

AU - Kong, A.

AU - Stefansson, K.

PY - 2007/1/1

Y1 - 2007/1/1

N2 - We conducted a genome-wide association study for type 2 diabetes (T2D) in Icelandic cases and controls, and we found that a previously described variant in the transcription factor 7-like 2 gene (TCF7L2) gene conferred the most significant risk. In addition to confirming two recently identified risk variants, we identified a variant in the CDKAL1 gene that was associated with T2D in individuals of European ancestry (allele-specific odds ratio (OR) = 1.20 (95% confidence interval, 1.13-1.27), P = 7.7 x 10(-9)) and individuals from Hong Kong of Han Chinese ancestry (OR = 1.25 (1.11-1.40), P = 0.00018). The genotype OR of this variant suggested that the effect was substantially stronger in homozygous carriers than in heterozygous carriers. The ORs for homozygotes were 1.50 (1.31-1.72) and 1.55 (1.23-1.95) in the European and Hong Kong groups, respectively. The insulin response for homozygotes was approximately 20% lower than for heterozygotes or noncarriers, suggesting that this variant confers risk of T2D through reduced insulin secretion.

AB - We conducted a genome-wide association study for type 2 diabetes (T2D) in Icelandic cases and controls, and we found that a previously described variant in the transcription factor 7-like 2 gene (TCF7L2) gene conferred the most significant risk. In addition to confirming two recently identified risk variants, we identified a variant in the CDKAL1 gene that was associated with T2D in individuals of European ancestry (allele-specific odds ratio (OR) = 1.20 (95% confidence interval, 1.13-1.27), P = 7.7 x 10(-9)) and individuals from Hong Kong of Han Chinese ancestry (OR = 1.25 (1.11-1.40), P = 0.00018). The genotype OR of this variant suggested that the effect was substantially stronger in homozygous carriers than in heterozygous carriers. The ORs for homozygotes were 1.50 (1.31-1.72) and 1.55 (1.23-1.95) in the European and Hong Kong groups, respectively. The insulin response for homozygotes was approximately 20% lower than for heterozygotes or noncarriers, suggesting that this variant confers risk of T2D through reduced insulin secretion.

U2 - 10.1038/ng2043

DO - 10.1038/ng2043

M3 - Article

C2 - 17460697

SN - 1061-4036

VL - 39

SP - 770

EP - 775

JO - Nature Genetics

JF - Nature Genetics

IS - 6

ER -

A variant in CDKAL1 influences insulin response and risk of type 2 diabetes

Abstract

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