Supplementary material: Human Adaptation to Arsenic-Rich Environments 1 15 Total SAC Sub SAC 10 density 5 0 0.0 0.2 0.4 0.6 iAs/AsAdj 25 20 15 density 10 5 0 0.00 0.05 0.10 0.15 0.20 MMA/AsAdj 3.0 2.0 density 1.0 0.0 0.0 0.5 1.0 1.5 2.0 DMA/AsAdj Figure S1: Phenotype density comparisons between the entire study population (385 women, in green) and the sample used for the association study and selection study (124 women, in blue), for 3 types of metabolites: inorganic arsenic (top panel), MMA (middle panel) and DMA (bottom panel), adjusted for the total arsenic content in urine. 2 Figure S2: Manhattan plots (FDR-corrected q-values) for %MMA (upper panel), %DMA (middle panel) and %inorganic arsenic from GWAS analyses. 3 Figure S3: Zoom-in of chromosome 10 region associated with %MMA and %DMA. 4 MMA Chr 3 MMA Chr 6 8 8 LOC440970 CADM2 LAMA2 BC035400 ARHGAP18C6orf191 L3MBTL3 SAMD3 TMEM200A 6 6 ● ● ● ● ● ● ● ● ● (P − value) ●●● ● (P − value) 4 ●● ●● ● 4 ● 10 ●● 10 ● ●●●●● ● ● ● ●●●●●●●●●●● 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in Mb MMA Chr 13 MMA Chr 21 8 8 MZT1BORAPIBF1 KLF5 KLF12AX748190AK056689 COL6A1 COL6A2DKFZp586E1322FTCDC21orf56LSS MCM3AP−AS1MCM3APYBEYC21orf58BC031638PCNT DIP2A S100B PRMT2 6 6 ● ● ● ● ●●● ●● ● ● ●●●● ● ● ● ● ● ●● (P − value) (P − value) ● ● ●● ● ● ●●● 4 ● 4 ●● ● 10 10 ● ● ●● ● ● ● ● ● ●● ● ●● ● ● ●●● −log −log ● ● ● ● ● ● ●● ●●● ● ● ● ● ● ● ● ● ● ● ●● ● ● ●● ● ●● ● ● ●●● ● ● ● ● ● ●● ● ● ● ● ● ● ● ● ● ●● ● ● ● ● ●● ● ●● ● ● ● ● ● ● ● ● ● ● ● ●● ● ● ● 2 ● 2 ●●● ●●●● ● ● ● ● ● ●● ●● ● ● ● ● ● ● ● ● ●● ● ● ● ● ●●● ●● ● ● ●● ●●● ●●●● ●●●● ● ● ● ● ● ● ●●●● ● ● ● ● ● ● ●● ● ●●● ●●●●● ● ● ● ●● ● ●● ● ● ●● ●● ● ● ●● ● ● ● ●● ●●●●●●●●● ● ● ● ●● ● ● ● ●●●●● ●● ● ●●● ● ● ● ● ● ●● ● ● ●●●●● ● ● ● ●●●● ●●● ● ● ●●● ●● ●● ● ● ●● ● ●●●●●●●●●●●●● ●● ● ● ● ● ●●● ● ●●●● ● ● ●●● ● ●● ● ●●●● ● ● ● ● ●●● ●● ●●●● ● ● ●●●●●●●●●●● ● ●●● ● ●● ● ● ● ●● ●● ● ● ● ● ● ●● ●● ●● ● ● ●●●● ●● ● ●●●●● ●●● ● ●● ● ● ●●●● ●● ● ● ●●● ● ●●●● ● ●●● ● ● ● ● ● ● ●●●●● ●● ● ●● ● ● ● ● ●● ● ● ● ● ●● ●●● ●● ●●● ●●●●● ●●●●● ●●● 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OR10P1METTL7BITGA7BLOC1S1RDH5CD63GDF11SARNPDNAJC14ORMDL2 MZT1BORAPIBF1 KLF5 KLF12AX748190AK056689AX747962LINC00347 6 6 ● ● ● ● ● ● ● ● ●●●● ● ● ● (P − value) (P − value) ● 4 4 10 ●● ● 10 ● ● ● ●●● ● ●● ● ● ● ● ● ● ● ●● −log ●●● ● ● ● −log ● ● ●● ●●●● ● ● ● ● ● ● ● ●● ● ● ● ●● ● ● ● ● ● ●● ● ● ● ● ● ● ● ●●●●●●●●● ●● ● ● ●● ●● ● ● ●● ● ●● ●● ● ●●●●●● ●● ● ● ● ● ● ●●● ● ● ● 2 ● ● ● ● ●● ● ● ● ● 2 ● ●● ● ●● ●●● ● ● ● ● ●● ●● ●● ● ● ● ● ● ● ● ● ● ● ● ● ● ●● ● ● ●● ● ●● ● ●● ● ● ● ●● ● ● ●● ● ● ● ●● ●●●●●●●● ● ● ● ● ● ● ● ● ● ●● ● ●●●● ●● ●● ●● ●● ● ●● ● ●●●● ● ●● ● ●●● ● ● ● ●●●●● ●●●●● ● ● ● ●●●● ●● ● ● ● ●●● ● ● ● ●●●● ● ● ● ● ●●● ● ● ● ●●●●● ●●● ● ●● ●●● ● ● ● ●● ● ●●● ●●● ●● ● ●● ● ●●●● ● ● ● ●● ●● ● ● ● ● ● ●● ● ● ●● ● ●● ● ● ● ●● ●● ●● ●● ● ● ● ● ● ●● ● ● ● ●● ● ● ● ●●● ●● ● ● ● ● ● ●●●● ●●● ● ●● ●● ● ● ● ●●● ●●● ●● ●●●● ● ● ●● ● ● ●● ● ●●●● ●●● ● ●●●● ● ● ● ● ● ● ●● ● ● ● ● ● ● ● ●● ●● ●● ●● ● ● ●●●● ●●● ●●● ● ● ●● ● ●● ●● ●●● ●● ●●●● ●●●●● ●● ●● ● ● ●●● ●●● ● ● ●●● ● ● ●●●● ● ● ● ●● 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