A variant in CDKAL1 influences insulin response and risk of type 2 diabetes
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A variant in CDKAL1 influences insulin response and risk of type 2 diabetes. / Steinthorsdottir, Valgerdur; Thorleifsson, Gudmar; Reynisdottir, Inga; Benediktsson, Rafn; Jonsdottir, Thorbjorg; Walters, G Bragi; Styrkarsdottir, Unnur; Gretarsdottir, Solveig; Emilsson, Valur; Ghosh, Shyamali; Baker, Adam; Snorradottir, Steinunn; Bjarnason, Hjordis; Ng, Maggie C Y; Hansen, Torben; Bagger, Yu; Wilensky, Robert L; Reilly, Muredach P; Adeyemo, Adebowale; Chen, Yuanxiu; Zhou, Jie; Gudnason, Vilmundur; Chen, Guanjie; Huang, Hanxia; Lashley, Kerrie; Doumatey, Ayo; So, Wing-Yee; Ma, Ronald C Y; Andersen, Gitte; Borch-Johnsen, Knut; Jorgensen, Torben; van Vliet-Ostaptchouk, Jana V; Hofker, Marten H; Wijmenga, Cisca; Christiansen, Claus; Rader, Daniel J; Rotimi, Charles; Gurney, Mark; Chan, Juliana C N; Pedersen, Oluf; Sigurdsson, Gunnar; Gulcher, Jeffrey R; Thorsteinsdottir, Unnur; Kong, Augustine; Stefansson, Kari.
In: Nature Genetics, Vol. 39, No. 6, 2007, p. 770-5.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - A variant in CDKAL1 influences insulin response and risk of type 2 diabetes
AU - Steinthorsdottir, Valgerdur
AU - Thorleifsson, Gudmar
AU - Reynisdottir, Inga
AU - Benediktsson, Rafn
AU - Jonsdottir, Thorbjorg
AU - Walters, G Bragi
AU - Styrkarsdottir, Unnur
AU - Gretarsdottir, Solveig
AU - Emilsson, Valur
AU - Ghosh, Shyamali
AU - Baker, Adam
AU - Snorradottir, Steinunn
AU - Bjarnason, Hjordis
AU - Ng, Maggie C Y
AU - Hansen, Torben
AU - Bagger, Yu
AU - Wilensky, Robert L
AU - Reilly, Muredach P
AU - Adeyemo, Adebowale
AU - Chen, Yuanxiu
AU - Zhou, Jie
AU - Gudnason, Vilmundur
AU - Chen, Guanjie
AU - Huang, Hanxia
AU - Lashley, Kerrie
AU - Doumatey, Ayo
AU - So, Wing-Yee
AU - Ma, Ronald C Y
AU - Andersen, Gitte
AU - Borch-Johnsen, Knut
AU - Jorgensen, Torben
AU - van Vliet-Ostaptchouk, Jana V
AU - Hofker, Marten H
AU - Wijmenga, Cisca
AU - Christiansen, Claus
AU - Rader, Daniel J
AU - Rotimi, Charles
AU - Gurney, Mark
AU - Chan, Juliana C N
AU - Pedersen, Oluf
AU - Sigurdsson, Gunnar
AU - Gulcher, Jeffrey R
AU - Thorsteinsdottir, Unnur
AU - Kong, Augustine
AU - Stefansson, Kari
PY - 2007
Y1 - 2007
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.
KW - Adult
KW - Blood Glucose
KW - Carrier Proteins
KW - Case-Control Studies
KW - Cross-Sectional Studies
KW - Diabetes Mellitus, Type 2
KW - Female
KW - Gene Frequency
KW - Genome, Human
KW - Humans
KW - Insulin
KW - Insulin Resistance
KW - Intracellular Signaling Peptides and Proteins
KW - Linkage Disequilibrium
KW - Male
KW - Middle Aged
KW - Nerve Tissue Proteins
KW - Polymorphism, Single Nucleotide
KW - TCF Transcription Factors
KW - Transcription Factor 7-Like 1 Protein
KW - Transcription Factor 7-Like 2 Protein
U2 - 10.1038/ng2043
DO - 10.1038/ng2043
M3 - Journal article
C2 - 17460697
VL - 39
SP - 770
EP - 775
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
IS - 6
ER -
ID: 38455034