Extended data 4 -. A common GCKR variant increases hepatic cytosolic NADH reductive stress.

(a) Gene structure, variant location, variant LD blocks, and haplotype frequency for risk haplotype of GCKR from the 1000 Genomes Project⁴⁵. AFR, Africa; EAS, East Asian; EUR, European; SAS, South Asian (b) Enrichment of redox sensitive metabolites in reported metabolite associations by loci from Rhee et al 2013. p values were determined from one-tailed Fisher’s exact test as described in Methods. (c) Effects of overexpression of Gckr or Gckr p.P446L in mouse primary hepatocytes. Data are mean ± s.e.m. Nominal p values were determined using paired two-sided Student’s T tests between n=5 independent hepatocyte isolations.