Publications
Nat1 Deficiency Is Associated with Mitochondrial Dysfunction and Exercise Intolerance in Mice.
Chennamsetty I, et al.
Cell Rep. 2016 Oct 4;17(2):527-540. doi: 10.1016/j.celrep.2016.09.005
Identification and validation of N-acetyltransferase 2 as an insulin sensitivity gene.
Knowles JW, et al.
J Clin Invest. 2015 Apr;125(4):1739-51. doi: 10.1172/JCI74692
Using Genetic Variants to Assess the Relationship Between Circulating Lipids and Type 2 Diabetes.
Fall T, et al.
Diabetes. 2015 Jul;64(7):2676-84. doi: 10.2337/db14-1710
Impact of type 2 diabetes susceptibility variants on quantitative glycemic traits reveals mechanistic heterogeneity.
Dimas AS, et al.
Diabetes. 2014 Jun;63(6):2158-71. doi: 10.2337/db13-0949
Mendelian randomization studies do not support a causal role for reduced circulating adiponectin levels in insulin resistance and type 2 diabetes.
Yaghootkar H, et al.
Diabetes. 2013 Oct;62(10):3589-98. doi: 10.2337/db13-0128
Detailed physiologic characterization reveals diverse mechanisms for novel genetic Loci regulating glucose and insulin metabolism in humans.
Ingelsson E, et al.
Diabetes. 2010 May;59(5):1266-75. doi: 10.2337/db09-1568
Dataset phenotypes
- insulin sensitivity
- insulin sensitivity adjusted for body mass index
Dataset subjects
| Cases | Controls | Cohort | Ancestry |
|---|---|---|---|
| 0 | 1,004 | RISC (Relationship between Insulin Sensitivity and Cardiovascular disease risk) | European |
| 0 | 899 | ULSAM (Uppsala Longitudinal Study of Adult Men) | European |
| 0 | 591 | EUGENE2 (European network on Functional Genomics of type 2 diabetes) | European |
| 0 | 270 | Stanford IST (Insulin Suppression Test) | European |
Project
The GENESIS (GENEticS of Insulin Sensitivity) consortium was formed to promote investigation of the genetics of insulin sensitivity.
Funding acknowledgments
The initial genotyping of the Stanford, SAPPHIRe and RISC samples was funded by Merck & Co, Inc. Work on the Stanford cohort was funded in part by a grant from the Stanford Cardiovascular Institute. Joshua W. Knowles was supported by an AHA Fellow-to-Faculty Transition Award. The RISC Study (Relationship between Insulin Sensitivity and Cardiovascular disease risk) was supported by an European Union grant and AstraZeneca. Timothy Frayling is supported by a European Research Council grant. EUGENE2 (European network on Functional Genomics of type 2 diabetes) was supported by a grant from the European Community’s FP6. ULSAM (Uppsala Longitudinal Study of Adult Men): Erik Ingelsson was supported by grants from the Swedish Research Council, the Swedish Heart-Lung Foundation, and the Swedish Foundation for Strategic Research while working with this project. Andrew P. Morris is a Wellcome Trust Senior Fellow in Basic Biomedical Science.
Experiment summary
Insulin sensitivity was tested for nondiabetic patients and was defined by the euglycemic clamp or insulin suppression tests.
RISC and Stanford samples were genotyped using the Affymetrix 6.0 microarray platform. ULSAM samples were genotyped using the Illumina Omni2.5M platform. EUGENE2 samples were genotyped using the Illumina 550K platform. Standard QC criteria were used for all studies, excluding samples that were duplicated or those with gender discordance or non-European ancestry. SNPs with genotyping call rate < 95%, Hardy-Weinberg equilibrium P-values < 0.0001 and MAF < 1% were excluded. Haplotypes were phased using MACH (RISC, EUGENE2, Stanford). Missing genotypes were imputed on the 1000 Genomes Project data (Interim 20101123 phase 1) against all-population reference panel using either MiniMac (52) (RISC, EUGENE2, Stanford) or IMPUTE (ULSAM). Additional details are available in (Knowles JW, et al. Identification and validation of N-acetyltransferase 2 as an insulin sensitivity gene.).