Study to Understand the Genetics of the Acute Response to Metformin and Glipizide in Humans (SUGAR-MGH)

We analyzed 890 participants at risk for type 2 diabetes from diverse ancestries who underwent sequential glipizide and metformin challenges. A genome-wide association study was performed using the Illumina Multi-Ethnic Genotyping Array. Imputation was performed with the TOPMed reference panel. Multiple linear regression using an additive model tested for association between variants with an imputation R2>0.8 and primary endpoints of drug response. Analyses were adjusted for age, sex, body mass index (BMI), and the first 10 ancestry principal components (PCs). Traits were rank-inverse normalized to avoid spurious associations driven by outliers or skewed distributions and beta estimates reflect rank-inverse normalization.

Each file contains summary statistics for 46 traits, including the following information:

chromosome(b38): chromosome number
position(b38): Position in b38
chrposID: markername in chr:pos:a1:a2 format
effect_allele: Effect allele
other_allele: Other allele
effect_allele_frequency: Effect allele frequency
beta: Effect estimate (rank-inverse normalization)
standard_error: Standard error of the effect estimate
p-value: p-value

Please refer any queries to Josephine H. Li (jli71@mgh.harvard.edu), Laura Brenner (LNBRENNER@partners.org), Varinderpal Kaur (VKAUR@mgh.harvard.edu), or Josep Mercader (mercader@broadinstitute.org).