a, Map of 1p13 SNPs genotyped in ~20,000 individuals of European descent relative to CELSR2 and PSRC1 genes. The six SNPs with strongest association with LDL-C (indicated with boxes), comprising a single haplotype, define the 6.1 kb region between the stop codons of the two genes. b, Firefly luciferase expression from constructs transfected into Hep3B human hepatoma cells. Both the major (darker colors) and minor (lighter colors) haplotypes of the 6.1 kb region were subcloned in forward and reverse orientations into a basal firefly luciferase construct with the SV40 promoter. Shown are ratios of firefly luciferase expression to Renilla luciferase expression (expressed from cotransfected plasmid), measured 48 hours after transfection, normalized to the mean ratio from the major haplotype, forward orientation construct. Error bars show s.e.m., N = 2. c, Both the major and minor haplotypes of a minimal 2.1 kb region were subcloned into the basal construct. Single nucleotide alterations were introduced individually into the minor haplotype, changing minor alleles of SNPs into major alleles. Shown are ratios of firefly luciferase expression to Renilla luciferase expression normalized to the mean ratio from the major haplotype construct. Error bars show s.e.m., N = 4.