Figure 3.

HbA_1c response to metformin treatment is diminished by SNPs in NBEA. A: Manhattan plot of HbA_1c response to metformin treatment when all races were combined (N = 1,312). The horizontal dashed lines represent suggestive statistical significance (P = 5 × 10⁻⁶) (bottom line) and genome-wide significance (P = 5 × 10⁻⁸) (top line). Each point represents a single SNP. Genotyped SNPs are represented with black dots, imputed SNPs are represented by blue dots, and SNPs meta-analyzed from subjects genotyped in Set 1 subjects and imputed in Set 2 subjects are represented by pink dots. B: A LocusZoom (48) plot demonstrating the lead SNP, rs57081354, association with change in HbA_1c when all races are combined. Linkage disequilibrium was calculated using the 1000 Genomes reference panel using the hg19/1000 Genomes Nov 2014 EUR selection, matching the panel used to perform imputation in ACCORD. C: Forest plot demonstrating associations of rs57081354 in available replication cohorts. The β values for REP1 were changed to the additive inverse to maintain a consistent direction of effect. A larger β value means a diminished metformin response. Data for rs57081354 were not available for REP2 and REP3. Bars represent the 95% CIs. D: Change in HbA_1c by rs57081354 genotype as represented by violin plots.