Table 3.
Attempt at replication of genome-wide significant findings from the DPP in the MetGen Consortium
| DPP model | Trait | rsID | DPP β* | MetGen (n) | MetGen β* | MetGen P value |
|---|---|---|---|---|---|---|
| MET | Weight, kg | rs186681623 | −2.66 (greater weight loss) | 10,519 | −0.05 (decreased HbA1c reduction) | 0.10 |
| MET | Weight, kg | rs17083791 | −1.85 (greater weight loss) | 12,578 | 0.004 (greater HbA1c reduction) | 0.79 |
| MET | Fasting insulin, ln | rs73944532 | −0.47 (greater decrease in fasting insulin) | 7,048 | 0.03 (greater HbA1c reduction) | 0.84 |
| G×T | Weight, kg | rs148219263 | 10.73 (reduced weight loss) | 10,519 | −0.04 (decreased HbA1c reduction) | 0.39 |
| G×T | Fasting glucose, mmol/L | rs75147163 | −0.73 (greater decrease in fasting glucose) | 10,288 | −0.02 (decreased HbA1c reduction) | 0.70 |
| G×T | HbA1c, % | rs12314996 | −0.47 (greater decrease in HbA1c) | 7,048 | 0.19 (greater HbA1c reduction) | 0.24 |
ln, natural log transformed; rsID, reference SNP ID.
*
In the DPP, the β estimates represent 1-year change in the quantitative trait as calculated by follow-up value minus baseline value. In MetGen, the outcome was change in HbA1c (%), defined as baseline value minus follow-up value within 18 months (will have opposite signs of β estimates for change in HbA1c compared with that in the DPP). For each analysis and cohort, the impact of the variant on the metformin response outcome is indicated in parentheses.