Extended Data Fig. 9: Identification of functional regulatory variants near the BLOC1S6 locus.
(a). rs72713175 overlaps a regulatory region in melanocytes. Green tracks indicate ATAC-seq for MNT-1 and WM88 cells; blue tracks indicate ATAC-seq and ChIP-Seq from NHM; orange tracks indicate CUT&RUN from MNT-1 cells. (b) MPRA results showing allelic skews at rs11985280 in WM88 cells but not in MNT-1 cells (n = 3). P values were estimated with a random effects model for mpralm and paired t-tests without multiple testing adjustments. For boxplots, central lines are median, with boxes extending from the 25th to the 75th percentiles. Whiskers further extend by ±1.5 times the interquartile range from the limits of each box. (c) Allele frequencies at rs72713175 in global populations, data were from the 180 G18 and 1000 G31 datasets. (d) LRA results showing that rs72713175 did not affect enhancer activity in WM88 and MNT-1 cells. Two-tailed paired t-tests (n = 6). (e) CRISPRi of the enhancer containing rs72713175 significantly reduced the expression of BLOC1S6 (control, n = 8; others, n = 6; Two-sided Dunnett’s test with adjustments for multiple comparisons). (f) CRISPRi of the enhancer containing rs72713175 significantly reduced melanin levels in MNT-1 cells (control, n = 18; others, n = 9, Two-sided Dunnett’s test with adjustments for multiple comparisons). Data are presented as mean ± SEM and p values are listed above the bars.
