Fig. 5. MPRA refines T2D-associated haplotype in SLC35D3 locus.

a Islet caQTL in the SLC35D3 locus. Two T2D SNPs, rs6937795 and rs6917676 (15 bps apart; r² = 0.99; green lines), are both significantly associated with altered chromatin accessibility changes (caQTLs) in the SLC35D3 locus in islets from 19 different individuals. b MPRA activity (log₂RNA/plasmid ratios) for each of the four possible rs6937795 and rs6917676 allelic combinations tested in the MPRA library. Only rs6917676 alleles altered MIN6 MPRA activity. The rs6917676 T allele is associated with both increased chromatin accessibility and MPRA activity. Shape/shading of points indicate the five paired biological replicates for each MPRA experiment. c Plot of InsPIRE Consortium islet eQTL -log10 association p-values between rs6917676 genotypes and expression of genes ± 1 megabase from the SNP. d MPRA activity (log₂RNA/plasmid ratio) of caQTL SNP rs6917676 (left), and two additional SNPs [rs947734 (red) and rs947735 (blue); 43 bp apart] that overlap the same SINE, in ER stress (Tg-treated) compared to DMSO control conditions. Red and blue dashed lines indicate relationships between alleles for each biological replicate. * denotes FDR < 10%. Box plots in panels (b) and (d) display the minimum, maximum, median, first quartile and third quartile of each data set. Points outside the minimum and maximum values are outliers.