DESCRIPTION:

List of positional candidate genes after correcting for multiple testing and controlling the false discovery rate from genome wide association studies (GWAS) retrieved from the NHGRI-EBI Catalog of published genome-wide association studies (http://www.ebi.ac.uk/gwas/). The disease/trait examined in this study, as reported by the authors, was Response to metformin in type 2 diabetes (glycemic). The EFO term response to metformin was annotated to this set after curation by NHGRI-EBI. Intergenic SNPS were mapped to both the upstream and downstream gene. P-value uploaded. This gene set was generated using gwas2gs v. 0.1.8 and the GWAS Catalog v. 1.0.1.

LABEL:

GWAS: response to metformin

SCORE TYPE:

P-Value

DATE ADDED:

2017-05-02

DATE UPDATED:

2024-04-25

SPECIES:

AUTHORS:

K Zhou, C Bellenguez, CC Spencer, AJ Bennett, RL Coleman, R Tavendale, SA Hawley, LA Donnelly, C Schofield, CJ Groves, L Burch, F Carr, A Strange, C Freeman, JM Blackwell, E Bramon, MA Brown, JP Casas, A Corvin, N Craddock, P Deloukas, S Dronov, A Duncanson, S Edkins, E Gray, S Hunt, J Jankowski, C Langford, HS Markus, CG Mathew, R Plomin, A Rautanen, SJ Sawcer, NJ Samani, R Trembath, AC Viswanathan, NW Wood, LW Harries, AT Hattersley, AS Doney, H Colhoun, AD Morris, C Sutherland, DG Hardie, L Peltonen, MI McCarthy, RR Holman, CN Palmer, P Donnelly, ER Pearson

TITLE:

Common variants near ATM are associated with glycemic response to metformin in type 2 diabetes.

JOURNAL:

Nature genetics Feb 2011, Vol 43, pp. 117-20

ABSTRACT:

Metformin is the most commonly used pharmacological therapy for type 2 diabetes. We report a genome-wide association study for glycemic response to metformin in 1,024 Scottish individuals with type 2 diabetes with replication in two cohorts including 1,783 Scottish individuals and 1,113 individuals from the UK Prospective Diabetes Study. In a combined meta-analysis, we identified a SNP, rs11212617, associated with treatment success (n = 3,920, P = 2.9 × 10(-9), odds ratio = 1.35, 95% CI 1.22-1.49) at a locus containing ATM, the ataxia telangiectasia mutated gene. In a rat hepatoma cell line, inhibition of ATM with KU-55933 attenuated the phosphorylation and activation of AMP-activated protein kinase in response to metformin. We conclude that ATM, a gene known to be involved in DNA repair and cell cycle control, plays a role in the effect of metformin upstream of AMP-activated protein kinase, and variation in this gene alters glycemic response to metformin. PUBMED: 21186350
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