METSIM GWAS

Dataset

Most samples in this dataset are included in the "DIAMANTE (European) T2D GWAS" dataset.

Publications

The Metabolic Syndrome in Men study: a resource for studies of metabolic and cardiovascular diseases.
Laakso M, et al.
J Lipid Res. 2017 Mar;58(3):481-493. doi: 10.1194/jlr.O072629

Dataset phenotypes

Phase 1 analysis:

type 2 diabetes
type 2 diabetes adjusted for BMI
fasting glucose
fasting glucose adjusted for BMI
fasting insulin
fasting insulin adjusted for BMI
HbA1c
HbA1c adjusted for BMI

Phase 2 analysis:

serum creatinine
systolic blood pressure
HDL cholesterol
eGFR-creat (serum creatinine)
diastolic blood pressure
LDL cholesterol
BMI

Dataset subjects

Cases

Controls

Cohort (Click to view selection criteria for cases and controls)

Ancestry

1,185

7,357

METSIM (METabolic Syndrome In Men)

European

Project

The METSIM (METabolic Syndrome In Men) study includes 10,197 men, aged from 45 to 73 years at entry, who were randomly selected from the population register of the Kuopio town, Eastern Finland, and were examined in 2005–2010. Subjects were phenotyped extensively, with emphasis on traits associated with type 2 diabetes (T2D), cardiovascular disease, and insulin resistance, and were genotyped using both Exome chip and OmniExpress chip technology.

Acknowledgments

This work was funded by grants from the Academy of Finland, the Juselius Foundation, the European Union, the European Medical Information Framework, the Finnish Heart Disease Research Foundation, and the Foundation for the National Institutes of Health.

Experiment summary

Most samples were genotyped using both Exome chip and OmniExpress chip technology.

Fasting glucose and fasting insulin levels were measured in blood samples taken from patients who had not had food or drink for at least 8 hours.

Overview of analysis and results

Data were analyzed by the Analysis Team at the Accelerating Medicines Partnership Data Coordinating Center (AMP-DCC), Broad Institute, using Loamstream software and the AMP-DCC Data Analysis Pipeline. Results are summarized below; see the Quality Control and Analysis Reports (links below) for full details.

One variant, rs12255372, in the region of the TCF7L2 gene was associated with T2D at genome-wide significance in both the unadjusted (p = 4.86 × 10⁻⁸) and BMI-adjusted (p = 2.96 × 10⁻⁹) models. These associations had been previously identified, and one additional association within the top 20 associations in the BMI-adjusted model had been previously identified.

In the BMI-unadjusted model, three associations with fasting glucose levels reached genome-wide significance: the variants rs579060 in the region of the ABCB11 gene, rs573225 in the region of the G6PC2 gene, and rs3847554 in the region of the MTNR1B gene, with p-values of 3.34 × 10⁻¹⁶, 4.55 × 10⁻¹⁵, and 1.17 × 10⁻¹³ respectively. All of these associations were identified previously, as were three additional associations within the top 20.

In the BMI-adjusted model, three associations with fasting glucose levels reached genome-wide significance: the variants rs552976 in the region of the ABCB11 gene, rs573225 in the region of the G6PC2 gene, and rs3847554 in the region of the MTNR1B gene, with p-values of 7.78 × 10⁻¹⁸, 2.02 × 10⁻¹⁷, and 5.34 × 10⁻¹⁶ respectively. All of these associations were identified previously, as were three additional associations within the top 20.

None of the fasting insulin associations reached genome-wide significance in the BMI-unadjusted model, and none of the top 20 associations had been identified previously. In the BMI-adjusted model, rs2943645 in the IRS1 gene was associated with a p-value of 2.08 × 10⁻¹⁰, and one other association in the top 20 had been identified previously.

The top association with HbA1c levels in both models was a novel association of rs1135071 in the region of the HBB gene, with p-values of 2.64 × 10⁻⁷² and 2.25 × 10⁻⁷¹ in the BMI-unadjusted and the BMI-adjusted models, respectively. In the BMI-unadjusted model, four additional associations reached genome-wide significance; one of these had been identified previously. Three additional associations in the top 20 of the BMI-unadjusted model had been identified previously. Five associations in the BMI-adjusted model, in addition to the top variant rs1135071, reached genome-wide significance. Three of these had been identified previously, and two additional associations within the top 20 had been identified previously.

None of the serum creatinine or systolic blood pressure associations reached genome-wide significance, and none had been identified previously.

Five associations with HDL cholesterol levels, all previously identified, reached genome-wide significance; the top association was rs173539 in the region of the CETP gene. Four additional associations within the top 20 were identified previously.

No associations with estimated glomerular filtration rate (eGFR) reached genome-wide significance. Two of the top 20 associations had been identified previously.

None of the associations with diastolic blood pressure reached genome-wide significance, and none had been identified previously.

All of the top 20 associations with LDL cholesterol reached genome-wide significance, and all had been identified previously.

The top association with BMI reached genome-wide significance and had been identified previously: rs9941349 in the region of the FTO gene. No other association in the top 20 had been identified previously.